1. CARLSBAD, Calif., Feb. 24, 2021 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today reported its financial results for the fourth quarter of 2020 and recent business highlights.

    "Last year, we laid out a bold new vision for the Company and took important steps towards our goal of becoming one of the most successful biotechnology companies. Key to our vision is our strategy to maximize the value of our pipeline by commercializing our wholly owned medicines. Our acquisition of Akcea was an important step in building our commercial capabilities while enabling us to further strengthen our organization," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "Last year, we also advanced our late-stage pipeline and expanded the utility of our technology. Looking ahead, we expect data from multiple wholly owned programs in the first half of this year, followed by Phase 3 tofersen data in patients with SOD1-ALS in the second half. These key upcoming catalysts, together with our recent pipeline and technology achievements, position us well to have 12 or more products on the market in 2026. Importantly, we continue to have the financial strength to expand investment in our wholly owned pipeline and commercial capabilities to drive meaningful and increasing value for patients and shareholders."

    2020 Summary Financial Results

    • Achieved 2020 financial guidance
      • $729 million in total revenues, with half from marketed products
      • $640 million of operating expenses on a non-GAAP basis(1) and $901 million on a GAAP basis, reflecting investments in Ionis' wholly owned pipeline
      • Net income of $111 million on a non-GAAP basis(1) and a net loss of $451 million on a GAAP basis
    • Strong balance sheet with cash of $1.9 billion at year-end, enabling increasing investment in advancing the pipeline and technology while also preparing to commercialize the Company's wholly owned medicines

    2020 Marketed Products Highlights 

    • SPINRAZA: a global foundation-of-care for the treatment of spinal muscular atrophy (SMA) patients of all ages
      • $2 billion in worldwide sales in 2020   
      • More than 11,000 patients worldwide were on therapy at the end of the fourth quarter across post-marketing, expanded access and clinical trial settings
      • Enrollment began in the RESPOND study evaluating potential SPINRAZA benefit in SMA patients with a suboptimal clinical response to gene therapy
      • Enrollment began in the pivotal randomized treatment cohort of the DEVOTE study evaluating higher doses of SPINRAZA
    • TEGSEDI and WAYLIVRA: transformational medicines approved for the treatment of patients with severe rare diseases
      • Product sales increased more than 65 percent in 2020, compared to 2019
      • Generated growing revenues as major markets launched in 2020
      • Restructured European operations through a distribution agreement with Swedish Orphan Biovitrum AB (Sobi)

    Q4 2020 and Recent Pipeline Highlights

    • Phase 3 Pipeline: growing pipeline positioned for 12 or more products on the market in 2026
      • Advanced IONIS-APOCIII-LRx into the Phase 3 BALANCE study in patients with FCS
      • Completed enrollment in the tofersen Phase 3 VALOR study in patients with SOD1-ALS
    • Mid-stage Pipeline: broad and advancing pipeline of potential first-in-class and/or best-in-class medicines
      • Advanced and expanded the IONIS-AGT-LRx development program
        • Reported IONIS-AGT-LRx positive topline Phase 2 results in patients with hypertension uncontrolled with two or three antihypertensive medications
        • Advanced ION904, the follow-on medicine targeting AGT, into Phase 1 development in healthy volunteers
      • Advanced vupanorsen into Phase 2b development with the initiation of the TRANSLATE-TIMI 70 dose-ranging study in statin-treated patients with dyslipidemia, resulting in a $75 million payment from Pfizer
      • Advanced ION449 (AZD8233), targeting PCSK9, into Phase 2b development in patients with dyslipidemia and AstraZeneca licensed ION455, a new investigational medicine for the treatment of nonalcoholic steatohepatitis (NASH), resulting in $50 million from AstraZeneca
      • Unlocked potential new pulmonary disease franchise with positive IONIS-ENAC-2.5Rx data
        • Reported positive healthy volunteer results supporting aerosol antisense medicine delivery to the lung
        • Completed dosing in the Phase 2 study in patients with cystic fibrosis
        • Advanced IONIS-ENAC-2.5Rx into Phase 2 development in patients with chronic obstructive pulmonary disease (COPD)
      • Highlighted IONIS-MAPTRx (BIIB080) Phase 1/2 study in patients with Alzheimer's disease in which IONIS-MAPTRx was generally well tolerated and demonstrated durable, time and dose-dependent reductions in CSF tau protein

    Upcoming 2021 Pipeline Catalysts 

    Anticipated 2021 Data Readouts(2)

    Program

    Phase

    Anticipated Indication

    H1

    H2

    IONIS-ENAC-2.5Rx

    2

    Cystic fibrosis



    IONIS-PKK-LRx

    2

    Hereditary angioedema (top-line)



    IONIS-GHR-LRx

    2

    Acromegaly (top-line)



    IONIS-AGT-LRx

    2

    Hypertension



    Tominersen

    OLE/NHS

    Huntington's disease

    IONIS-MAPTRx

    1/2

    Alzheimer's disease



    Vupanorsen

    2b

    sHTG/CVD risk reduction



    IONIS-C9Rx

    1/2

    C9-ALS



    Tofersen

    3 (VALOR study)

    SOD1-ALS



    Anticipated 2021 Study Initiations(2)

    Program

    Phase

    Anticipated Indication

    H1

    H2

    ION363

    3

    FUS-ALS



    ION373

    2

    Alexander disease



    IONIS-AGT-LRx

    2b

    Resistant hypertension



    IONIS-AGT-LRx

    2

    Heart failure with reduced ejection fraction



    ION224

    2b

    NASH



    Tofersen

    3 (ATLAS study)

    Presymptomatic SOD1-ALS

    IONIS-APOCIII-LRx

    3

    Second CV indication



    IONIS-ENAC-2.5Rx

    2

    Cystic fibrosis not amenable to CFTR modulators





    (2) Timing of partnered program catalysts based on partners' most recent publicly available disclosures

    2020 Financial Results and 2021 Financial Guidance

    "We achieved our 2020 financial guidance, even in the challenging COVID-19 pandemic environment. Moreover, in 2020 we made significant progress toward our goal of creating a stronger, more efficient company focused primarily on advancing our wholly owned medicines to the market. We acquired Akcea enabling us to retain full value from its rich portfolio. We also restructured our European operations. Together, these transactions unlocked substantial cost savings that we plan to reinvest to drive future revenue growth," said Elizabeth L. Hougen, chief financial officer of Ionis. "Our 2021 guidance reflects our new strategy to maximize the value of our wholly owned pipeline, focused primarily on commercializing our rare neurological and cardiometabolic disease programs. Our guidance also reflects the investments we are making in three key areas of our business - advancing and expanding our wholly owned pipeline, building commercial capabilities in support of our rich pipeline and broadening the reach of our technology. We can increase our investments in these areas while only modestly increasing our expenses because of the significant cost savings we realized from acquiring Akcea and restructuring our European operations. Importantly, with nearly $2 billion of cash at the end of last year, we remain well capitalized with the substantial financial resources to achieve our goals."

    2021 Financial Guidance

    Ionis' full year 2021 financial guidance consists of the following components (on a non-GAAP basis)(1):

    Guidance

    Revenue

    >$600 million

    Operating Expenses (1)

    $675 million to $725 million

    Net Loss (1)                                  

    <$75 million











    (1)

    All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards and expenses related to the Akcea acquisition and restructured European operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Acquisition and Restructured European Operations" for a breakdown of the costs specific to these transactions. Additionally, please refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this release.

    Revenue

    Ionis' revenue was comprised of the following (amounts in millions):





    Three months ended,



    Year ended,





    December 31,



    December 31,





    2020



    2019



    2020



    2019

    Revenue:













         Commercial revenue:

















    SPINRAZA royalties



    $75



    $81



    $287



    $293

    Product sales, net



    19



    13



    70



    42

    Licensing and royalty revenue



    2



    6



    8



    17

    Total commercial revenue



    96



    100



    365



    352

    R&D Revenue:

















    Amortization from upfront payments



    12



    46



    80



    146

    Milestone payments



    110



    51



    183



    115

    License fees



    71



    292



    86



    490

    Other services



    1



    5



    15



    20

    Total R&D revenue



    194



    394



    364



    771

    Total revenue



    $290



    $494



    $729



    $1,123

    Financial Impacts of Akcea Acquisition and Restructured European Operations

    In the fourth quarter of 2020, the Company's non-GAAP amounts exclude the following expenses related to the Akcea acquisition and restructured European operations because the costs are not part of its normal ongoing operating activities. Refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this release. (Amounts in millions):





    Three months ended

    December 31, 2020

         Severance, retention and other expenses



    $31

    Non-cash stock-based compensation expense for the acceleration of Akcea equity awards



    59

    Total expenses included in GAAP operating expenses



    $90

    Non-cash adjustment of the valuation allowance for Ionis' federal net deferred tax assets and other tax adjustments related to the Akcea acquisition



    312

    Total expenses included in GAAP net loss



    $402

    As a result of the Akcea acquisition, Ionis and Akcea began reporting their federal taxes on a consolidated basis in the fourth quarter of 2020. The Company recorded a valuation allowance against all Ionis' federal net deferred tax assets in the fourth quarter of 2020, due largely to Akcea's history of losses and the expected impact of this on Ionis' consolidated federal taxable income. The Company now maintains a valuation allowance against all its consolidated federal and state net deferred tax assets.

    Operating Expenses

    Ionis' operating expenses for the year ended December 31, 2020 increased compared to 2019 driven by the Company's investments in advancing the Phase 3 programs for IONIS-TTR-LRx, IONIS-APOCIII-LRx and other medicines in its wholly owned pipeline. Additionally, the Company incurred approximately $90 million in costs related to the Akcea acquisition and restructured European operations on a GAAP basis. The costs consisted of $31 million of severance, retention and other costs and $59 million of non-cash stock-based compensation expense for the acceleration of Akcea equity awards.

    Net Loss Attributable to Noncontrolling Interest in Akcea

    Prior to completing its acquisition of Akcea in October 2020, Ionis owned approximately 76 percent of Akcea. The line titled "Net loss attributable to noncontrolling interest in Akcea" on Ionis' statement of operations reflects the portion of Akcea's net income or loss attributable to the other owners of Akcea's common stock. From mid-October 2020 through December 31, 2020, Ionis did not recognize any noncontrolling interest in Akcea on its statement of operations because it owned 100 percent of Akcea. Beginning in 2021, the Company will no longer have an adjustment for noncontrolling interest in Akcea.

    Net Income (Loss) Attributable to Ionis Common Stockholders

    Ionis recognized a net loss attributable to Ionis' common stockholders for 2020 compared to net income in 2019 primarily due to higher revenue in 2019, including approximately $400 million in license fees Ionis earned from Pfizer and Novartis. Also contributing to Ionis' net loss in 2020 was the non-cash adjustment of the valuation allowance Ionis recorded against its federal net deferred tax assets discussed above. Additionally, Ionis' operating expenses increased in 2020 compared to the same period last year as described above.

    Balance Sheet

    Ionis ended 2020 with cash, cash equivalents and short-term investments of $1.9 billion, compared to $2.5 billion at December 31, 2019. In October 2020, Ionis used approximately $545 million of its cash for the Akcea acquisition.

    Webcast

    Today, at 9:00 a.m. Eastern Time, Ionis will conduct a live webcast to discuss this earnings release and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals, Inc.

    For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing the standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies. 

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen) and WAYLIVRA (volanesorsen) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen. 

    IONIS PHARMACEUTICALS, INC.

    SELECTED FINANCIAL INFORMATION

    Condensed Consolidated Statements of Operations

    (In Millions, Except Per Share Data)







    Three months ended,



    Year ended,





    December 31,



    December 31,





    2020



    2019



    2020



    2019



















    (unaudited)

    Revenue:

















         Commercial revenue:

















    SPINRAZA royalties



    $75



    $81



    $287



    $293

    Product sales, net



    19



    13



    70



    42

    Licensing and royalty revenue



    2



    6



    8



    17

    Total commercial revenue



    96



    100



    365



    352

        Research and development revenue under collaborative agreements



    194



    394



    364



    771

    Total revenue



    290



    494



    729



    1,123

    Expenses:

















           Cost of products sold



    3



    1



    12



    4

        Research, development and patent



    171



    149



    535



    466

        Selling, general and administrative



    139



    83



    354



    287

    Total operating expenses



    313



    233



    901



    757



















    Income (loss) from operations



    (23)



    261



    (172)



    366



















    Other income (loss), net



    (1)



    (23)



    2



    (19)

    Income (loss) before income tax benefit (expense)



    (24)



    238



    (170)



    347





































    Income tax benefit (expense)



    (318)



    (34)



    (317)



    (44)



















    Net income (loss)



    ($342)



    $204



    ($487)



    $303

    Net loss (income) attributable to noncontrolling interest in Akcea Therapeutics, Inc.



    2



    (20)



    36



    (9)

    Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders



    ($340)



    $184



    ($451)



    $294



















    Basic net income (loss) per share



    ($2.44)



    $1.31



    $(3.23)



    $2.12

    Diluted net income (loss) per share



    ($2.44)



    $1.28



    $(3.23)



    $2.08

    Shares used in computing basic net income (loss) per share



    140



    141



    140



    140

    Shares used in computing diluted net income (loss) per share



    140



    153



    140



    143

     

    IONIS PHARMACEUTICALS, INC.

    Reconciliation of GAAP to Non-GAAP Basis:

    Condensed Consolidated Operating Expenses, Income (Loss) From Operations, and Net Income (Loss)

    (In Millions)







    Three months ended,

    December 31,



    Year ended,

    December 31,





    2020



    2019



    2020



    2019





    (unaudited)

    As reported operating expenses according to GAAP



    $313



    $233



    $901



    $757

        Excluding compensation expense related to equity awards      



    (36)



    (35)



    (171)



    (147)

        Excluding Akcea acquisition and restructured European operations costs



    (90)



    -



    (90)



    -



















    Non-GAAP operating expenses



    $187



    $198



    $640



    $610



















    As reported income (loss) from operations according to GAAP



    ($23)



    $261



    ($172)



    $366

        Excluding compensation expense related to equity awards



    (36)



    (35)



    (171)



    (147)

    Excluding Akcea acquisition and restructured European operations costs



    (90)



    -



    (90)



    -

    Non-GAAP income (loss) from operations



    $103



    $296



    $89



    $513



















    As reported net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders according to GAAP



    ($340)



    $184



    ($451)



    $294



















    Excluding compensation expense related to equity awards attributable to Ionis Pharmaceuticals, Inc. common stockholders



    (36)



    (33)



    (162)



    (139)



















    Income tax effect related to compensation expense related to equity awards attributable to Ionis Pharmaceuticals, Inc. common stockholders



    (16)



    5



    2



    31

     Excluding Akcea acquisition and restructured European operations costs



    (90)



    -



    (90)



    -

    Income tax effect related to the Akcea acquisition and restructured European operations costs



    (312)



    -



    (312)



    -

    Non-GAAP net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders



    $114



    $212



    $111



    $402

    Reconciliation of GAAP to Non-GAAP Basis

    As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (loss) attributable to Ionis Pharmaceuticals, Inc. common shareholders were adjusted from GAAP to exclude compensation expense related to equity awards and costs related to the Akcea acquisition and restructured European operations and the related tax effects. Compensation expense related to equity awards are non-cash. Costs related to the Akcea acquisition and restructured European operations include: severance costs, retention costs, other costs, non-cash stock-based compensation expense for the acceleration of Akcea equity awards and non-cash income tax expense as a result of establishing a valuation allowance for Ionis' federal net deferred tax assets. Ionis has regularly reported non-GAAP measures for operating results as non-GAAP results. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations.

    IONIS PHARMACEUTICALS, INC.

    Condensed Consolidated Balance Sheets

    (In Millions)



















    December 31,



    December 31,







    2020



    2019















    Assets:











      Cash, cash equivalents and short-term investments



    $1,892



    $2,500



      Contracts receivable



    76



    63



      Other current assets



    162



    158



      Property, plant and equipment, net



    181



    154



      Other assets



    79



    358



         Total assets



    $2,390



    $3,233















    Liabilities and stockholders' equity:











      Other current liabilities



    $182



    $155



      Current portion of deferred contract revenue



    108



    118



      1% convertible senior notes (current in 2020)



    293



    275



      0.125% convertible senior notes



    456



    435



      Long-term obligations, less current portion



    84



    75



      Long-term deferred contract revenue



    424



    490



      Total Ionis stockholders' equity



    843



    1,471



      Noncontrolling interest in Akcea Therapeutics, Inc.



    -



    214



      Total stockholders' equity



    $843



    $1,685



        Total liabilities and stockholders' equity



    $2,390



    $3,233

















     

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  2. CARLSBAD, Calif., Feb. 19, 2021 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in RNA-targeted therapeutics, today announced that management will participate in a virtual fireside chat at the following investor conferences:

    • SVB Leerink 10th Annual Global Healthcare Conference on Friday, February 26, 2021;
    • Oppenheimer 31st Annual Healthcare Conference on Wednesday, March 17, 2021; and
    • J.P. Morgan 10th Annual Napa Valley Forum on Monday, March 29, 2021.

    The above listed dates are subject to change. Details on presentation times or changes to presentation dates can be found on the Company's website. Please check www.ionispharma.com for the latest information.

    A live webcast of the presentations will be available on the Investors & Media section of the Ionis website. The replays will be available within 48 hours and will be archived for a limited time.

    About Ionis Pharmaceuticals

    For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

     

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  3. CARLSBAD, Calif., Feb. 11, 2021 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that it will host a live webcast on Wednesday, February 24th at 9:00 a.m. Eastern Time to discuss its 2020 financial results and report on pipeline and business progress.

    Interested parties may access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals

    For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies. 

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

     

     

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    • The global Phase 4 RESPOND study will evaluate the efficacy and safety of SPINRAZA in patients with a suboptimal clinical response to Zolgensma
    • Clinical and real-world experience have reported that some patients previously treated with Zolgensma have also been treated with SPINRAZA1,2,3,4
    • Biogen remains committed to exploring the potential of SPINRAZA to optimize outcomes for patients with SMA

    CAMBRIDGE, Mass., Jan. 08, 2021 (GLOBE NEWSWIRE) -- Biogen Inc. (NASDAQ:BIIB) today announced that the first patient has been treated in the global clinical study, RESPOND. The Phase 4 study will examine the clinical benefit and assess the safety of SPINRAZA® (nusinersen) in infants and children with spinal muscular atrophy (SMA) who still have unmet clinical…

    • The global Phase 4 RESPOND study will evaluate the efficacy and safety of SPINRAZA in patients with a suboptimal clinical response to Zolgensma

    • Clinical and real-world experience have reported that some patients previously treated with Zolgensma have also been treated with SPINRAZA1,2,3,4
    • Biogen remains committed to exploring the potential of SPINRAZA to optimize outcomes for patients with SMA

    CAMBRIDGE, Mass., Jan. 08, 2021 (GLOBE NEWSWIRE) -- Biogen Inc. (NASDAQ:BIIB) today announced that the first patient has been treated in the global clinical study, RESPOND. The Phase 4 study will examine the clinical benefit and assess the safety of SPINRAZA® (nusinersen) in infants and children with spinal muscular atrophy (SMA) who still have unmet clinical needs following treatment with gene therapy Zolgensma® (onasemnogene abeparvovec). RESPOND will be conducted at approximately 20 sites worldwide and aims to enroll up to 60 children with SMA.

    "SMA treatments have changed what is possible for children born with the disease but they have also raised new questions," said Dr. Nicole Gusset, President of SMA Europe and mother of a child with SMA. "We appreciate that the RESPOND study will collect data to help provide answers so individuals living with SMA can make informed treatment decisions."

    Children with SMA do not produce enough survival motor neuron (SMN) protein, which is critical for the maintenance of motor neurons that support sitting, walking and basic functions of life like breathing and swallowing. The RESPOND study will seek to understand if the proven efficacy of SPINRAZA and its mechanism of action, which leads to continuous production of SMN protein, may also benefit patients who have been insufficiently treated with gene therapy.

    "In clinical practice, there is a sense of urgency to address motor neuron loss in SMA from the earliest sign or even prior to symptoms, to prevent additional disease progression," said Julie Parsons, M.D., professor of Clinical Pediatrics and Neurology and Haberfeld Family Endowed Chair in Pediatric Neuromuscular Disorders at Children's Hospital Colorado and the University of Colorado School of Medicine, and primary investigator of the RESPOND study. "In some patients treated with gene therapy, we have recognized that further motor neuron protection may be needed. Our hope is that results from RESPOND will demonstrate if SPINRAZA can optimize treatment for some of our youngest patients."

    RESPOND is a two-year, open-label study to evaluate the efficacy and safety of SPINRAZA in SMA patients previously treated with Zolgensma to further optimize treatment decisions. The primary endpoint is the total score on the Hammersmith Infant Neurological Examination Section 2. Secondary endpoints include safety, change from baseline on additional motor function measures, other clinical outcomes (e.g., swallowing) and caregiver burden. Neurofilament levels, an exploratory endpoint, will also be evaluated as a marker of biological disease activity.

    The study will enroll 60 children up to 3 years old who are determined by the investigator to have the potential for additional clinical improvement after receiving Zolgensma. It has been reported that, to date, 40 percent of children in the long-term study of Zolgensma have been subsequently treated with SPINRAZA.1 Physicians will use criteria that may include one or more of the following: suboptimal motor function (e.g., a score lower than 50 on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]); the need for respiratory support; abnormal swallowing or feeding ability; or other factors deemed relevant by the investigator.

    The primary study group will include 40 infants aged 9 months or younger (at the time of first SPINRAZA dose) who have 2 copies of SMN2 (likely to develop SMA Type 1) and received Zolgensma at 6 months old or younger. A second study group will include 20 children within a broader age range (up to 3 years old at the time of first SPINRAZA dose). After a screening period, participants will receive the approved 12 mg dose of SPINRAZA: four loading doses, followed by maintenance doses every four months,5 over the two-year study period.

    More information on the study (NCT04488133) is available at clinicaltrials.gov.

    About SPINRAZA® (nusinersen)

    SPINRAZA is approved to treat infants, children and adults with spinal muscular atrophy (SMA) and is available in more than 50 countries. As a foundation of care in SMA, more than 11,000 individuals have been treated with SPINRAZA worldwide.6

    SPINRAZA is an antisense oligonucleotide (ASO) that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.5 It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.5

    SPINRAZA has demonstrated sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 7 years, combined with unsurpassed real-world experience.7 The SPINRAZA clinical development program encompasses 10 clinical studies, which have included more than 300 individuals across a broad spectrum of patient populations,7 including two randomized controlled studies (ENDEAR and CHERISH). The ongoing SHINE and NURTURE open-label extension studies are evaluating the long-term impact of SPINRAZA. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs.

    Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics. Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country's product website.

    About Spinal Muscular Atrophy (SMA)

    SMA is a rare, genetic, neuromuscular disease that affects individuals of all ages. It is characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness.8 SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missing SMN1 gene, with a spectrum of disease severity.8 Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time.9 In the absence of treatment, children with the most severe form of SMA would not be expected to reach their second birthday.8

    SMA impacts approximately one in 11,000 live births,10 is a leading cause of genetic death among infants10 and causes a range of disability in teenagers and adults.9

    About Biogen

    At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world's first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer's disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

    We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media – TwitterLinkedInFacebookYouTube.

    Biogen Safe Harbor 

    This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of SPINRAZA; the results of certain real-world data; the identification and treatment of SMA; our research and development program for the treatment of SMA; the potential benefits and results from early treatment of SMA; the enrollment of the RESPOND study; risks and uncertainties associated with drug development and commercialization; and the potential of our commercial business, including SPINRAZA. These statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "intend," "may," "plan," "possible," "potential," "will," "would" and other words and terms of similar meaning. You should not place undue reliance on these statements or the scientific data presented.

    These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation risks that we may not fully enroll the RESPOND study or it will take longer than expected; unexpected concerns that may arise from additional data, analysis or results obtained during the RESPOND study; the occurrence of adverse safety events; risks of unexpected costs or delays; the risks of other unexpected hurdles; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

    References:

    1. Zolgensma EU Summary of Product Characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/product-information/zolgensma-epar-product-information_en.pdf. Accessed: December 2020.
    2. Finkel R, et al. Presented at the Muscular Dystrophy Association (MDA) 2020 Clinical & Scientific Conference.
    3. Harada Y, et al. Presented at the Muscular Dystrophy Association (MDA) 2020 Clinical & Scientific Conference.
    4. Finkel R, et al. Presented at the World Muscle Society's (WMS) 2020 Virtual Congress.
    5. SPINRAZA U.S. Prescribing Information. Available at: https://www.spinraza.com/content/dam/commercial/specialty/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf. Accessed: December 2020.
    6. Based on commercial patients, early access patients, and clinical trial participants through September 30, 2020. 
    7. Core Data Sheet, Version 9, January 2019. SPINRAZA. Biogen Inc, Cambridge, MA.
    8. National Institute of Neurological Disorders and Stroke, NIH. Spinal Muscular Atrophy Fact Sheet. Available at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Spinal-Muscular-Atrophy-Fact-Sheet. Accessed: December 2020.
    9. Wadman RI, Wijngaarde CA, Stam M, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c–4. Eur J Neurol. 2018;25(3):512-518.
    10. Cure SMA. About SMA. Available at https://www.curesma.org/about-sma/. Accessed: December 2020.
    MEDIA CONTACT:

    David Caouette

    + 1 617 679 4945

    INVESTOR CONTACT:

    Joe Mara

    +1 781 464 2442



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  4. CARLSBAD, Calif., Jan. 7, 2021 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced the appointment of Eugene Schneider, M.D., as executive vice president and chief clinical development officer. In this role, Dr. Schneider will oversee clinical development of novel antisense medicines across all of Ionis' therapeutic franchises. He will report to Richard S. Geary, Ph.D., Ionis' executive vice president and chief development officer, and serve on the company's executive team.

    Since joining Ionis in 2013, Dr. Schneider has played a key role in more than 20 clinical trials conducted in the U.S. and globally. He is an accomplished biopharmaceutical industry veteran with two decades of experience leading global medical and scientific affairs and the development and commercialization of medicines to treat a range of disorders, including pediatric, rare and central nervous system diseases.

    "Dr. Schneider's proven track record overseeing successful studies, assessing risk-benefit profiles of investigational medicines and providing consistent clinical due diligence in safety reporting will strengthen Ionis' industry leadership as we expand our portfolio of wholly owned and partnered medicines and build our commercial organization to maximize the value of our rich pipeline," said Dr. Geary.

    "I am excited to join Ionis' talented executive team and look forward to continuing my work with them and all Ionis employees who are deeply committed to delivering potentially transformative medicines to patients who depend on us," said Dr. Schneider.   

    Before joining Ionis, Dr. Schneider was senior medical director, clinical research and development at Synageva BioPharma, where he developed a novel enzyme replacement therapy for Lysosomal Acid Lipase Deficiency from its first-in-man study to registration. Prior to Synageva, he was senior medical director, medical and scientific affairs at Biovail Technologies Ltd., where he was primarily responsible for the development and commercialization of a diverse portfolio of medicines designed to address patient needs related to central nervous system disorders.

    Dr. Schneider received his medical degree from the University of Medicine and Dentistry of New Jersey and completed his training in pediatric and adolescent medicine at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.

    ABOUT IONIS PHARMACEUTICALS, INC. 

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

     

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    SOURCE Ionis Pharmaceuticals, Inc.

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  5. CARLSBAD, Calif., Dec. 17, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in RNA-targeted therapeutics, announced today that its founder and executive chairman Stanley T. Crooke, M.D., Ph.D., will retire from Ionis and its board of directors effective June 2021. Dr. Crooke is stepping down so that he may focus on his scientific interests and the nonprofit organization he founded, the n-Lorem Foundation. Dr. Crooke will continue to serve as a scientific advisor to Ionis including providing advice regarding Ionis' research and development programs and guiding the core antisense research group he founded at Ionis.

    Dr. Crooke founded Ionis more than 30 years ago and is credited with being the pioneer of RNA-targeted therapeutics. Under his leadership, Ionis developed its novel antisense technology and created one of the largest, most advanced pipelines in the industry. He has personally led the development of more than 20 marketed drugs throughout his career and supported the creation and growth of several companies based on Ionis' antisense technology. In addition, Dr. Crooke is responsible for creating one of the most innovative and scientifically driven cultures that has an unwavering passion for discovering and developing future-creating therapies and a steadfast commitment to saying yes to the patients who are depending on them.

    "The brilliance of Stan's vision isn't just represented by the founding and success of Ionis, but it is also reflected in his creation of an entirely new chemical class of medicines, antisense oligonucleotides," said Joseph Loscalzo, M.D., Ph.D., head, Department of Medicine and Physician-in-Chief, Brigham & Woman's Hospital, Harvard Medical School and Ionis board member. "His scientific contributions will no doubt continue to provide extraordinary benefit to the healthcare industry and the many patients who once were told there isn't any hope or treatment for their disease. With Stan solely focusing on his scientific interests and n-Lorem, we can only expect his impact to continue."

    Dr. Crooke has received numerous honors and awards for his pioneering work in RNA-targeted therapeutics including the prestigious Massry Prize, the Oligonucleotide Therapeutics Society Lifetime Achievement Award, the American Chemical Society's E.B. Hershberg Award for Important Discoveries in Medicinally Active Substances, the Prix Galien Best Biotechnology Award for Spinraza, the Scrip Lifetime Achievement Award, and BIO's Helix Award for the most important innovation. In addition, Ionis' board of directors named the main headquarters building in honor of Dr. Crooke in 2019 to recognize his extraordinary role in creating Ionis. Dr. Crooke has published nearly 600 scientific publications, edited more than 20 books, and is a named inventor on numerous patents.

    "Thanks to Stan's vision and perseverance, thousands of patients are benefiting from the transformative and life-changing antisense medicines discovered and developed by Ionis," said Brett P. Monia, Ph.D., Ionis chief executive officer. "We are pleased that Stan will continue to provide advice and counsel to Ionis and applaud his efforts to use the technology that was created at Ionis to bring hope and therapies to the patients who will benefit greatly from the n-Lorem foundation."

    n-Lorem Foundation, founded in 2019 by Dr. Crooke and initially funded by him, his wife Dr. Rosanne Crooke, Ionis and Biogen, provides free individualized antisense treatments to patients living with ultra-rare diseases (1 to 30 patients worldwide) for life. In less than a year of its founding, the Foundation has garnered support from global partners such as the Korean Institute of Toxicology, many donors, has received more than 40 requests for treatment and has 10 patients being treated or about to be treated with an investigational antisense medicine that was designed for each one's specific genetic mutation that's causing their disease.  

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  6. CARLSBAD, Calif., Dec. 8, 2020 /PRNewswire/ -- At its Investor Day yesterday, Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) highlighted the company's significant achievements in 2020 and outlined its strategy to realize the substantial opportunity of its pipeline.

    Ionis has been preparing and prioritizing its growing wholly owned pipeline for commercialization in line with its commercial strategy. The company's commercial priorities are three-fold: (1) Initially focusing its commercial efforts on rare diseases within its prolific neurology and cardiology franchises (2) pioneer new markets where there are no available treatments (3) create new standards of care where there has been a lack of innovation to optimize patient care.  

    Delivering on these three priorities will have meaningful impact to patients, their families, and healthcare providers all while reducing the burden on healthcare systems and driving value for all Ionis' stakeholders including patients and shareholders.

    Ionis also has plans to expand opportunistically to new products in additional treatment areas such as hematology, endocrinology and pulmonology.

    Ionis projects having the opportunity to launch six or more new products through 2026, with each being ready for launch in a close window, ranging from 18 to 24 months between each new product launch. The expectation is that the implementation of this strategy will drive double-digit revenue growth and substantial earnings growth.

    Brett P. Monia, Ph.D., chief executive officer at Ionis, said, "In 2020, we pursued an aggressive agenda focused on building our commercial plans and capabilities, progressing the Ionis-owned pipeline, advancing our technology and growing our leadership position in RNA-targeted therapeutics. We are pleased to say that we delivered against all these objectives. We invested in building our commercial plans and capabilities and began implementation. These actions were accelerated through the acquisition of our commercial affiliate Akcea. We have also progressed and substantially expanded the Ionis-owned pipeline. In addition, we have six Phase 3 trials underway, initiated 13 Phase 2 trials, achieved multiple, positive clinical proof-of-concept readouts, and advanced new delivery platforms."

    Dr. Monia continued, "For years we have been recognized for our excellence in research, early drug development and scientific innovation. We will now add to this by building a strong and efficient commercial organization of equal excellence. All of which will provide substantial benefit to patients and shareholders for years to come."

    Highlights of Investor Day

    • Ionis estimates the total market opportunity for the indications targeted by its pipeline is well in excess of $15 billion, with a significant portion from its wholly owned medicines.
    • Ionis' cardiovascular franchise includes many potential first-in-class and/or best-in-class medicines targeting a full spectrum of cardiovascular disease risk factors. The company is positioned to potentially launch multiple Ionis-owned cardiovascular medicines through 2026, including:

       
      • AKCEA-APOCIII-LRx: One product with the potential for addressing multiple indications targeting elevated triglycerides and the opportunity to set a new standard of care for triglyceride management
        • 91% of patients achieved normal serum triglycerides levels with favorable safety and tolerability in Phase 2
        • As announced on Dec. 1, 2020, a Phase 3 study in patients with familial chylomicronemia syndrome (FCS) is now underway
        • Evaluating additional indications with plans to initiate an additional Phase 3 study in 2021
      • AKCEA-TTR-LRx: Opportunity to significantly expand ATTR franchise
        • Robust target reductions of more than 90% and favorable safety and tolerability demonstrated in Phase 1
        • Flexibility of at-home monthly self-administration
        • Two Phase 3 studies underway – CARDIO-TTRransform for patients with hereditary or wild type TTR cardiomyopathy and NEURO-TTRansform for patients with hereditary TTR polyneuropathy. 
      • IONIS-AGT-LRx: Large unmet need in patients with treatment-resistant hypertension (RHTN)
        • Two Phase 2 clinical studies: Patients with mild HTN and patients with uncontrolled HTN who are on two (65%) or three (35%) antihypertensive medications 
        • Positive Phase 2 study in patients in uncontrolled HTN: patients achieved mean reductions of 12 mmHg and 6 mmHg in systolic and diastolic blood pressure from their own baseline, respectively, after eight weeks of once-weekly 80 mg IONIS-AGT-LRx
        • IONIS-AGT-LRx has demonstrated a favorable safety and tolerability profile in clinical trials to date
        • More detailed results to be presented at an upcoming medical conference
    • Ionis' neurology franchise has the potential to establish the standard of care for millions of patients and generate substantial value as it advances its first-in-class medicines to the market. The neurological disease market is a nascent market poised for substantial growth. Ionis believes it can be the catalyst for this growth as it is positioned to launch multiple Ionis-owned medicines through 2026, including:

         
      • ION363: First medicine in development to specifically target FUS-ALS, a rare, rapidly progressing form of ALS
        • Pivotal study on track for initiation in 2021
        • Potential for a rapid path to the market
      • ION716: Potential to be first approved treatment for prion diseases
        • Designed to reduce production of prion protein, root cause of prion disease
        • Pursuing pre-symptomatic (genetic carriers) and symptomatic (genetic and sporadic) indications
        • Pivotal study planned for 2021, design should provide a rapid path to market

    Akcea Integration Update

    The recently completed acquisition of Akcea has created a stronger, more efficient company, further bolstering Ionis' financial strength. The integration of Akcea is ahead of schedule, delivering cost synergies and efficiencies. It was also announced that Akcea is going to commercialize TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB ("Sobi"), an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, Akcea retains the marketing authorization ("MAH") for both medicines in Europe. Additionally, Akcea will continue to maintain limited European operations including regulatory, manufacturing, and the management of relationships with key opinion leaders. Akcea will continue to lead the TEGSEDI and WAYLIVRA global commercial strategy. The agreement provides Ionis the flexibility to reinvest resources to support its other commercial plans.

    Oral Delivery Development Update

    Ionis and AstraZeneca are committed to bringing the best possible PCSK9 antisense treatments to patients and have been collaborating on both the subcutaneous and oral formulations. The subcutaneous formulation of ION449 has a potential best-in-class profile and is advancing rapidly toward Phase 3 development.

    Preclinical and early clinical data give Ionis and AstraZeneca confidence that they can achieve effective oral delivery of ION449 and other ASOs.  Based on ongoing research and experience to date, both companies believe they can improve upon the current oral formulation. Therefore, Ionis and AstraZeneca have decided to terminate the Phase 1 PCSK9 oral study. Ionis and AstraZeneca will continue to broadly work together to further optimize the oral delivery of ASOs, including ION449.

    Ionis is expanding its oral delivery to include medicines from its pipeline and has increased its internal investment in oral delivery research. The company plans on initiating one or more programs from its pipeline within the next year or two. Candidates for consideration include IONIS-TTR-LRx, IONIS-PKK-LRx, ION994 (AGT), and ION547. Success would further enhance the commercial value of Ionis-owned programs.

    Webcast

    Additional details are available in the replay of the webcast. It is available here for a limited time.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    Forward-looking Statements

    This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of SPINRAZA® (nusinersen), TEGSEDI® (inotersen), WAYLIVRA® (volanesorsen) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019 and our most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of this and other documents are available at www.ionispharma.com. In this presentation, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  7. CARLSBAD, Calif., Dec. 2, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, today announced that management will participate in a virtual fireside chat at the BMO 2020 Growth and ESG Conference at 3:00 p.m. E.T. on Tuesday, December 8, 2020.

    Interested parties may access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  8. CARLSBAD, Calif., Dec. 1, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced the initiation of the Phase 3 BALANCE study for AKCEA-APOCIII-LRx in adult patients with familial chylomicronemia syndrome (FCS). FCS is a debilitating genetic disease characterized by severely high plasma levels of triglycerides and a risk of unpredictable and potentially fatal acute pancreatitis. In addition to acute pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic diabetes. AKCEA-APOCIII-LRx is designed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform and is designed to inhibit production of apolipoprotein C-III…

    CARLSBAD, Calif., Dec. 1, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced the initiation of the Phase 3 BALANCE study for AKCEA-APOCIII-LRx in adult patients with familial chylomicronemia syndrome (FCS). FCS is a debilitating genetic disease characterized by severely high plasma levels of triglycerides and a risk of unpredictable and potentially fatal acute pancreatitis. In addition to acute pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic diabetes. AKCEA-APOCIII-LRx is designed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform and is designed to inhibit production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of serum triglycerides.

    "Initiation of the Phase 3 BALANCE study is a significant milestone for the FCS patient community and for our company. This study also reflects our continuing commitment to develop novel treatment options for patients with unmet medical needs such as those living with FCS," said Richard S. Geary, Ph.D., executive vice president of development. "AKCEA-APOCIII-LRx is the second Ionis antisense medicine that we are developing with FCS patients in mind. We are hopeful about the prospect of bringing forward a new, safe, and effective treatment since these patients have limited available options."

    The Phase 3 BALANCE study is a global, multi-center, randomized, double-blind, placebo-controlled study enrolling up to 60 patients (age 18 and over) with FCS. Participants will be randomized in a 2:1 ratio to receive AKCEA-APOCIII-LRx or placebo via subcutaneous injection once every four weeks for a total 53-week treatment period. The primary endpoint is percent change from baseline in fasting triglyceride levels at six months compared to placebo. Following the treatment period, eligible patients will have the option of enrolling in an open-label extension study. In addition to FCS, Ionis is evaluating additional indications for AKCEA-APOCIII-LRx development. More information on the BALANCE study is available at www.clinicaltrials.gov/NCT04568434.

    AKCEA-APOCIII-LRx is one of 20 potentially transformative antisense programs in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization. Learn more about some of these programs at Ionis' Virtual Investor Day on Dec. 7, 2020 at 11 a.m. EST.

    About FCS

    FCS is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia (>880mg/dL or 10mmol/L) and a risk of unpredictable and potentially fatal acute pancreatitis. Because of limited LPL production or function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90 percent triglycerides. In addition to pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic (type 3c) diabetes. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognition that affect their ability to work. People with FCS also report major emotional and psychosocial effects including anxiety, social withdrawal, depression and brain fog. Additional information on FCS is available at www.fcsfocus.com, through Action FCS at https://www.actionfcs.org/ and through The FCS Foundation at http://www.livingwithfcs.org. For a full list of organizations supporting the FCS community worldwide, please click here.

    ABOUT AKCEA-APOCIII-LRx

    AKCEA-APOCIII-LRx is an investigational antisense medicine designed to reduce the production of apolipoprotein C-III, or apoC-III. ApoC-III is a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Genetically reduced levels of apoC-III are correlated to lower levels of triglycerides and lower risk of cardiovascular disease whereas elevated levels of apoC-III correlate with high triglyceride levels that have been associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome as well as elevated cardiovascular event risk. AKCEA-APOCIII-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. AKCEA-APOCIII-LRx is in Phase 3 development for patients with FCS, with plans to evaluate AKCEA-APOCIII-LRx in patients with other hypertriglyceridemia disorders. AKCEA-APOCIII-LRx was discovered and developed by Ionis.

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of AKCEA-APOCIII-LRx and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company. 

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    SOURCE Ionis Pharmaceuticals, Inc.

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  9. CARLSBAD, Calif., Dec. 1, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that it will host a live investor day webcast on Monday, December 7th at 11:00 a.m. Eastern Time to provide an overview of its commercial strategy, key opportunities in its cardiovascular and neurological franchises and recent technology advances. The approximately 3-hour webcast will include presentations from Brett P. Monia, Ph.D., chief executive officer; Sam Tsimikas, M.D., senior vice president, global cardiovascular development; C. Frank Bennett, Ph.D., chief scientific officer; Onaiza Cadoret, chief corporate development and commercial officer; Beth Hougen, chief financial officer; and Eric Swayze, Ph.D., executive vice president…

    CARLSBAD, Calif., Dec. 1, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that it will host a live investor day webcast on Monday, December 7th at 11:00 a.m. Eastern Time to provide an overview of its commercial strategy, key opportunities in its cardiovascular and neurological franchises and recent technology advances. The approximately 3-hour webcast will include presentations from Brett P. Monia, Ph.D., chief executive officer; Sam Tsimikas, M.D., senior vice president, global cardiovascular development; C. Frank Bennett, Ph.D., chief scientific officer; Onaiza Cadoret, chief corporate development and commercial officer; Beth Hougen, chief financial officer; and Eric Swayze, Ph.D., executive vice president, research. The agenda for the webcast will be as follows:

    Welcome and introductions

    Wade Walke

    Where we are today

    Brett Monia

    Key commercial opportunities in Ionis' cardiovascular franchise

    Sam Tsimikas

    Key commercial opportunities in Ionis' neurological franchise

    Frank Bennett

    Commercial strategy

    Onaiza Cadoret

    Valuing Ionis' pipeline

    Beth Hougen

    Increasing our leadership position in RNA-targeted therapeutics

    Eric Swayze

    2021 and beyond

    Brett Monia

    Q&A

    All

    Interested parties may access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

     

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    SOURCE Ionis Pharmaceuticals, Inc.

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  10. CARLSBAD, Calif., Nov. 30, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced that the biopharmaceutical company AstraZeneca has initiated a Phase 2b clinical trial of ION449 (AZD8233), an investigational antisense medicine designed to reduce blood cholesterol levels in patients with dyslipidemia by targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), an important regulator of low-density lipoprotein cholesterol (LDL-C). PCSK9 is an enzyme that controls the number of LDL receptors on the surface of cells. People with genetic variations that reduce PCSK9 function have lower LDL-C levels in the blood and a lower risk for major cardiovascular events. ION449 is a LIgand Conjugated Antisense (LICA) medicine…

    CARLSBAD, Calif., Nov. 30, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced that the biopharmaceutical company AstraZeneca has initiated a Phase 2b clinical trial of ION449 (AZD8233), an investigational antisense medicine designed to reduce blood cholesterol levels in patients with dyslipidemia by targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), an important regulator of low-density lipoprotein cholesterol (LDL-C). PCSK9 is an enzyme that controls the number of LDL receptors on the surface of cells. People with genetic variations that reduce PCSK9 function have lower LDL-C levels in the blood and a lower risk for major cardiovascular events. ION449 is a LIgand Conjugated Antisense (LICA) medicine being developed by AstraZeneca as part of a collaboration between Ionis and AstraZeneca.

    The Phase 2b, randomized, double-blind, placebo-controlled trial will enroll approximately 108 participants, aged 18-75, who have LDL-C levels between 70 and 190 mg/dL and are receiving moderate- or high-intensity statin therapy as defined by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines on blood cholesterol management. The primary objective is to assess the effect of different doses of ION449 on LDL-C compared to placebo at Week 12 in patients taking baseline statin therapy.  The study will evaluate three dose levels of ION449 versus placebo, all administered once a month by subcutaneous injection. Safety and tolerability will be evaluated along with a number of secondary endpoints. Learn more about the trial at: https://clinicaltrials.gov/ct2/show/NCT04641299

    In a Phase 1 study reported at the American Heart Association (AHA) Scientific Sessions on November 13, single subcutaneous doses of ION449 (AZD8233) demonstrated dose-dependent mean reductions in circulating plasma PCSK9 and LDL-C levels of >90 percent and up to 70 percent, respectively, in subjects who had a baseline LDL-C between 100 and 190 mg/dL without concomitant statin therapy.Doses up to 120 mg were evaluated. ION449 was observed to be safe and well-tolerated at all dose levels. 

    "Results from the Phase 1 study showed that ION449 potently reduces PCSK9 and LDL cholesterol. ION449 demonstrated best-in-class potential for PCSK9 inhibition and LDL-C reduction, supporting larger clinical trials that are now underway to further evaluate efficacy and safety," said Sotirios "Sam" Tsimikas, M.D., senior vice president, clinical development and cardiovascular franchise leader at Ionis. "The growing evidence supporting Ionis' advanced LICA technology in cardiovascular disease holds promise for more effective approaches to lower LDL-C and to address cardiovascular disease, the leading cause of death worldwide."

    Dr. Tsimikas will provide an update on Ionis' cardiovascular programs during Ionis' Virtual Investor Day, Dec. 7, 2020, beginning at 12 p.m. EST.

    Ionis earned a milestone payment of $20 million from AstraZeneca for the Phase 2b clinical trial initiation of ION449. Ionis and AstraZeneca are collaborating on potential treatments for kidney disease, cardiometabolic disease and cancer.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of ION449 (AZD8233), Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticalsä is a trademark of Ionis Pharmaceuticals, Inc.

    1 Clinical study (NCT03593785), sponsored by AstraZeneca.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  11. CARLSBAD, Calif., Nov. 23, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that the biopharmaceutical company AstraZeneca has licensed ION455, an investigational antisense medicine being developed as a potential treatment for nonalcoholic steatohepatitis (NASH). ION455 is the second medicine for the treatment of NASH that Ionis has partnered with AstraZeneca. The companies have also partnered on ION839 (AZD2693), which is designed to inhibit the production of patatin-like phospholipase domain-containing 3 (PNPLA3) protein, a major genetic determinant of NASH progression. Separately, Ionis is also developing a wholly owned NASH program. ION224 is designed to reduce the production of DGAT2, or diacylglycerol acyltransferase…

    CARLSBAD, Calif., Nov. 23, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that the biopharmaceutical company AstraZeneca has licensed ION455, an investigational antisense medicine being developed as a potential treatment for nonalcoholic steatohepatitis (NASH). ION455 is the second medicine for the treatment of NASH that Ionis has partnered with AstraZeneca. The companies have also partnered on ION839 (AZD2693), which is designed to inhibit the production of patatin-like phospholipase domain-containing 3 (PNPLA3) protein, a major genetic determinant of NASH progression. Separately, Ionis is also developing a wholly owned NASH program. ION224 is designed to reduce the production of DGAT2, or diacylglycerol acyltransferase 2, for treating patients with NASH. ION224 is one of more than 20 medicines in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization.

    NASH is the most severe form of nonalcoholic fatty liver disease (NAFLD). It is related to the epidemic of obesity, pre-diabetes and diabetes. Unlike liver disease caused by alcohol consumption, NAFLD is the result of an accumulation of fat in the liver, which can lead to inflammation and cirrhosis, an advanced scarring of the liver that prevents the liver from functioning normally. About 20 percent of NASH patients are reported to develop cirrhosis and 30 to 40 percent of patients with NASH cirrhosis experience liver-related death.i Currently, a liver transplant is the only treatment for advanced cirrhosis and liver failure. Because of the high prevalence of NASH, it has recently become the third most common indication for liver transplantation in the U.S.

    "Today, there are no FDA-approved medicines to specifically treat nonalcoholic steatohepatitis. However, due in large part to the progress made by our cardio-metabolic franchise, three Ionis-discovered novel medicines are now in development. These are encouraging advances that we hope will one day bring therapeutic benefit to patients who have limited treatment options," said Brett P. Monia, Ph.D., Ionis' chief executive officer. 

    ION455 is the fourth medicine to reach development in partnership with AstraZeneca. Ionis earned $30 million from AstraZeneca for licensing ION455 and is eligible to earn up to $300 million in milestone payments plus royalties on net sales. AstraZeneca will have responsibility for further development of ION455, including regulatory filings, and commercialization.

    In addition to NASH, Ionis and AstraZeneca are collaborating on potential treatments for kidney disease, cardiovascular disease and cancer.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of ION455, ION839 (AZD2693), ION224 and Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    i Takahashi, Y. et al.  (2015) Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 21, 3777-3785

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    SOURCE Ionis Pharmaceuticals, Inc.

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  12. CARLSBAD, Calif., Nov. 13, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that new data for ION449, an investigational antisense medicine designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9, or PCSK9, were presented today at the American Heart Association (AHA) Scientific Sessions. PCSK9 is integrally involved in the regulation of LDL-cholesterol (LDL-C). Genetic studies have shown that individuals with life-long reduction of LDL-C due to reduced function of PCSK9 have substantially reduced risk of cardiovascular disease.

    ION449, also known as AZD8233 for subcutaneous administration and AZD6615 for oral administration, is being developed as part of a collaboration between Ionis and the biopharmaceutical company AstraZeneca. ION449 incorporates Ionis' advanced Generation 2.5 and LIgand Conjugated Antisense, or LICA, technology. In a Phase 1 study, single subcutaneous doses of ION449 demonstrated dose-dependent reductions in circulating plasma PCSK9 protein and LDL-C levels of up to >90 percent and up to ~70 percent, respectively, in humans with a baseline LDL-C between 100 and 190 mg/dL.Doses of 4, 12, 20, 30, 60, 90 and 120 mg were evaluated. The single 90 mg dose was the minimum dose required to achieve maximum reduction in PCSK9 and LDL-C. ION449 was observed to be safe and well tolerated at all dose levels.

    In addition, the feasibility of oral administration of ION449 was established in three in vivo studies:

    • A study in rats demonstrated liver bioavailability of 5 percent with ION449 following intrajejunal administration, mimicking oral administration of tablets not feasible in rodents.
    • A study in dogs demonstrated liver bioavailability of 7 percent following ION449 oral tablet administration for 28 days.
    • A study in healthy monkeys found repeated oral administration of ION449 tablets for 14 days resulted in LDL-cholesterol reductions of 45–50 percent.

    An oral formulation of ION449 is currently being evaluated in a Phase 1 study in healthy volunteers.

    "Even with existing treatments, cardiovascular disease remains the leading cause of death worldwide, affecting tens of millions of people. Additional treatments are clearly needed for patients still at risk. The data from these studies are very encouraging and demonstrate the best-in-class potential of ION449 for lowering LDL-C via PCSK9 reduction for the treatment of patients with high cholesterol who are at risk of cardiovascular disease," said Brett P. Monia, Ph.D., chief executive officer at Ionis.

    The full poster presentations, "Single Dose Safety, Pharmacokinetics, and Pharmacodynamics of a Potent PCSK9 Synthesis Inhibitor, AZD8233, in Subjects With Elevated LDL Cholesterol" (Poster #MP515) and "An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans" (Poster #P244) are available to view on the AHA Scientific Sessions website.

    Ionis' collaboration with AstraZeneca focuses on leveraging Ionis' pioneering antisense technology to discover and develop antisense therapies and AstraZeneca's expertise in drug development and commercialization. In addition to cardiovascular programs, the companies are also collaborating to discover and develop antisense drugs to treat cancer, metabolic and other diseases.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of ION449 (AZD8233 or AZD6615), Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticalsä is a trademark of Ionis Pharmaceuticals, Inc.

    1 Clinical study (NCT03593785), sponsored by AstraZeneca.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  13. CARLSBAD, Calif., Nov. 12, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), announced today the upcoming presentations of clinical and non-clinical data for several of its investigational antisense medicines for cardiovascular disease at the American Heart Association (AHA) Scientific Sessions 2020, to be held virtually November 13-17, 2020. 

    Two of the abstracts accepted for presentation will provide new data from studies of ION449, also known as AZD8233 for subcutaneous administration and AZD6615 for oral administration. ION449 is an investigational antisense medicine targeting PCSK9, which is integrally involved in the regulation of LDL-cholesterol. ION449 is being developed as part of a collaboration between Ionis and the biopharmaceutical company AstraZeneca. Data presented include a study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of ION449 in patients with elevated LDL-cholesterol and a separate pre-clinical study evaluating this investigational medicine for once-daily oral dosing.

    Additional presentations by Ionis scientists will include a review of RNA-targeted treatments designed to inhibit the production of apolipoprotein C-III (apoC-III) and lipoprotein(a) or Lp(a). The apoC-III protein is an independent cardiovascular risk factor that regulates triglyceride metabolism in the blood. Ionis' AKCEA-APOCIII-LRx is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of apoC-III for patients who are at risk for cardiometabolic disease due to elevated triglyceride levels. AKCEA-APOCIII-LRx is expected to start a Phase 3 study in patients with familial chylomicronemia syndrome (FCS) by year end. Elevated Lp(a) is an independent, genetic risk factor for cardiovascular disease that cannot be well controlled with lifestyle modifications such as diet or exercise or with treatment using existing lipid-lowering therapies. Ionis' pelacarsen is an investigational LICA medicine designed to reduce the production of apolipoprotein(a) in patients who are at risk for cardiometabolic disease due to high Lp(a). Pelacarsen is currently in a Phase 3 cardiovascular outcomes study.

    Following are presentations of Ionis programs and collaborations:

    Cardiovascular Seminars:

    • Friday, November 13, 11:10 a.m. CST 'Experimental Therapy for APOCIII Lowering: ASO, siRNA,' Rosanne Crooke, Ph.D., senior strategic consultant at Ionis
    • Friday, November 13, 11:20 a.m. CST 'Experimental Therapy for Lp(a) Lowering,' Sotirios "Sam" Tsimikas, M.D., Ph.D., senior vice president, clinical development and leader, cardiovascular franchise

    Poster Presentations in Collaboration with AstraZeneca:

    • Friday, November 13, 9:00 a.m. CST 'An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans' (Poster #P244)
    • Friday, November 13, 9:00 a.m. CST 'Single Dose Safety, Pharmacokinetics, and Pharmacodynamics of a Potent PCSK9 Synthesis Inhibitor, AZD8233, in Subjects With Elevated LDL Cholesterol' (Poster #MP515)

    A full list of presentations can be found on the AHA Scientific Sessions website.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding Ionis' business, the therapeutic and commercial potential of our products, Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals is a trademark of Ionis Pharmaceuticals, Inc.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  14. CARLSBAD, Calif., Nov. 10, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that accomplished Ionis scientists will highlight the company's pioneering advancements in research and drug development in antisense technology during the RNA at the Bench and Bedside II Conference, to be held virtually Nov. 11-13, 2020. Plenary session presentations will include a review of the cardiovascular Phase 3 clinical trials Lp(a) HORIZON evaluating pelacarsen and CARDIO-TTRansform evaluating AKCEA-TTR-LRx; updates on how medicines developed using Ionis' advanced LIgand-Conjugated Antisense (LICA) technology are showing promise as potential treatments for heart failure and metabolic diseases; and a discussion on technology advances…

    CARLSBAD, Calif., Nov. 10, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that accomplished Ionis scientists will highlight the company's pioneering advancements in research and drug development in antisense technology during the RNA at the Bench and Bedside II Conference, to be held virtually Nov. 11-13, 2020. Plenary session presentations will include a review of the cardiovascular Phase 3 clinical trials Lp(a) HORIZON evaluating pelacarsen and CARDIO-TTRansform evaluating AKCEA-TTR-LRx; updates on how medicines developed using Ionis' advanced LIgand-Conjugated Antisense (LICA) technology are showing promise as potential treatments for heart failure and metabolic diseases; and a discussion on technology advances in the delivery of antisense medicines, including oral and aerosol administration.

    More than 30 speakers from across industry and academia will present at the conference, which is sponsored by Ionis, University of California San Diego School of Medicine, Nature Biotechnology and Nature Structural & Molecular Biology. The conference was inspired by Ionis founder and executive chairman of the board Stanley T. Crooke, M.D., Ph.D., who pioneered antisense technology and RNA-targeted therapeutics more than 30 years ago.

    "As the leader in RNA-targeted therapeutics, Ionis is excited to participate in the RNA at the Bench and Bedside II Conference, which this year emphasizes clinical advances in cardiovascular and metabolic diseases. Ionis has established vast experience in cardio-metabolic diseases and this, along with many breakthrough advances in our technology, have created a rich pipeline of potential first-in-class medicines to treat a wide range of cardio-metabolic diseases with significant unmet medical need," said Brett P. Monia, Ph.D., Ionis' chief executive officer.

    Following are Ionis presentations scheduled for the conference:

    • Using ligand conjugated oligonucleotides for the treatment of metabolic disease, Richard Lee, Ph.D., executive director, antisense drug discovery
    • How antisense drugs work: molecular mechanisms of cellular pharmacokinetics, pharmacodynamics and toxicity, KEYNOTE IV, Stanley T. Crooke, M.D., Ph.D., founder and executive chairman of the board
    • Targeted delivery of ASO therapeutics, Punit Seth, Ph.D., vice president, medicinal chemistry
    • RNA-targeted therapies for heart failure, Adam Mullick, Ph.D., vice president, drug discovery
    • RNA-targeted therapeutics for cardiovascular disease, Sotirios "Sam" Tsimikas, M.D., Ph.D., senior vice president, clinical development and leader, cardiovascular franchise
    • Characterization of phase separation in different phosphorothioate oligonucleotide-containing subcellular structures, Xue-Hai Liang, executive director, core antisense research

    In addition to plenary sessions, numerous posters by Ionis scientists will be presented during the conference:

    • Integrated assessment of Phase 2 studies on GalNAc3-conjugated 2'-o-methoxyethyl modified chimeric antisense oligonucleotides, Brenda Baker, Ph.D., executive director, development communications
    • Population PKPD modeling of ION-682884, an antisense oligonucleotide in development for treatment of transthyretin amyloidosis, John Diep, M.S., PharmD, assistant director, preclinical development
    • Enhanced antisense oligonucleotide delivery via AGTR1 targeting, Carol Kuo, Ph.D., senior research associate, antisense drug discovery
    • Lipid based permeation enhancers potentiated sodium caprate-dependent oral bioavailability of GalNAc3-conjugated antisense oligonucleotides following intra-jejunal dosing in rats, Kaustubh Kulkarni, M.S., Ph.D., assistant director, preclinical development
    • Subcellular fractionation and evaluation of hepatic cells after antisense oligonucleotide treatment in mice, Sue Murray, director, antisense drug discovery
    • Mechanism-based population pharmacokinetic/pharmacodynamic (PKPD) Modeling of IONIS-TMPRSS6-LRx to guide early clinical development, Charvi Nanavati, Ph.D., principal scientist, preclinical development
    • Pre-mRNA levels can be increased due to enhanced transcription by certain RNase H1-dependent antisense oligonucleotides, Joshua Nichols, senior research associate, core antisense research
    • Towards a mechanistic understanding of ASO-mediated innate immune responses, Adam Pollack, Ph.D., senior scientist, core antisense research
    • DYRK1a antisense oligonucleotides conjugated to GLP-1R agonist promote pancreatic beta cell proliferation, Andy Powers, Ph.D., assistant director, metabolic drug discovery
    • Inhibition of the nonsense mediated decay pathway and translation termination machinery by antisense oligonucleotides upregulate nonsense-mutated CFTR expression and function, Eddie Sanderlin, Ph.D., postdoctoral fellow, antisense drug discovery
    • Binding of phosphorothioate oligonucleotides with RNase H1 protein can cause conformational changes and alter the interactions of RNase H1 with other proteins, Lingdi Zhang, Ph.D., senior scientist, core antisense research

    Ionis collaborators and partners will also present on Ionis research and clinical development stage programs during the conference:

    • Targeted delivery of RNA therapeutics to pancreatic β-cells, Shalini Andersson, AstraZeneca, USA
    • RNA targeting therapies for thromboembolic disorders, Harry Buller, Academic Medical Center, Amsterdam
    • Antisense therapy has contributed to understanding and therapy of hyperlipoproteinemia KEYNOTE VI: Joe Witztum, University of California San Diego, USA
    • Lp(a) an under recognized CV disease risk, Tom Thuren, Novartis, USA

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/ionis-antisense-technology-to-be-featured-during-virtual-rna-at-the-bench-and-bedside-ii-conference-301169264.html

    SOURCE Ionis Pharmaceuticals, Inc.

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  15. CARLSBAD, Calif., Nov. 9, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, today announced that management will present a company overview at the following virtual investor conferences:

    • Stifel 2020 Healthcare Conference on Monday, November 16, 2020;
    • Evercore ISI 3rd Annual HealthCONx Conference on Tuesday, December 1, 2020; and
    • Piper Sandler 32nd Annual Healthcare Conference on Thursday, December 3, 2020.

    The above listed dates are subject to change. Details on presentation times or changes to presentation dates can be found on the Company's website. Please check www.ionispharma.com for the latest information.

    A live webcast of the presentations will be available on the Investors & Media section of the Ionis website. The replays will be available within 48 hours and will be archived for a limited time.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/ionis-to-present-at-upcoming-virtual-investor-conferences-301168132.html

    SOURCE Ionis Pharmaceuticals, Inc.

    View Full Article Hide Full Article
  16. CARLSBAD, Calif., Nov. 4, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today reported its financial results for the third quarter of 2020 and recent business highlights.

    "We took an important step forward in our evolution when we acquired Akcea. This transaction supports our commercial strategy, further enabling us to maximize the value of our Ionis-owned pipeline. As one company, we believe we are stronger and more efficient, with an enhanced ability to achieve even greater future success," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "We made significant progress across our pipeline this year. Recently, we advanced inhaled delivery with IONIS-ENAC-2.5Rx, positioning us to bring new treatment options to patients with pulmonary diseases. We also initiated mid-stage studies for vupanorsen in cardiovascular disease patients and ION541, our medicine to treat nearly all forms of ALS. Additionally, our five Phase 3 studies continue to progress, with our sixth expected to begin by the end of this year. We believe our achievements this year move us closer to delivering 10 or more marketing applications through 2025. Our goal is to bring these medicines to millions of patients around the world."

    Third Quarter 2020 Financial Results and Highlights

    • On track to achieve financial guidance of being meaningfully profitable this year
      • Net income of $5 million on a non-GAAP basis and a net loss of $31 million on a GAAP basis for the third quarter
    • Achieved quarter over quarter revenue growth
      • Commercial revenue from SPINRAZA® (nusinersen) royalties of $74 million, in line with the prior quarter
      • Product sales from TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen) increased more than 15 percent
      • R&D revenue increased more than 15 percent from advancing several partnered programs
    • Maintained a strong balance sheet with cash of $2.3 billion
      • Estimated pro forma cash following the Akcea acquisition of $1.8 billion

    "Our acquisition of Akcea further strengthens our business and financial position in numerous ways. We now retain more value from Akcea's rich pipeline and commercial products. We are also able to use Akcea's current cash and future cash flows to advance Ionis' strategic priorities. And beginning next year, we expect to realize meaningful cost synergies as we continue to integrate the two companies," said Elizabeth L. Hougen, chief financial officer of Ionis. "Looking ahead, we are maintaining our 2020 financial guidance driven by the significant revenue and earnings growth we expect in the fourth quarter. We have already earned revenue from multiple sources this quarter, including $75 million from Pfizer for advancing vupanorsen. Importantly, we remain well capitalized with the financial resources to achieve our strategic goals."

    All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of non-GAAP and GAAP measures, which is provided later in this release.

    Commercial Medicine Highlights 

    • SPINRAZA: a global foundation-of-care for the treatment of spinal muscular atrophy (SMA) patients of all ages
      • $495 million in worldwide sales in the third quarter
      • More than 11,000 patients were on SPINRAZA treatment worldwide at the end of the third quarter, including patients across commercial, expanded access and clinical trial settings
      • The open-label safety cohort of the DEVOTE study of higher-dose SPINRAZA is fully enrolled and the pivotal randomized treatment cohort will begin enrolling patients next
      • The Phase 4 RESPOND study in patients with a suboptimal clinical response to gene therapy is expected to begin early next year
    • TEGSEDI: the only approved at-home subcutaneous therapy for the treatment of hereditary transthyretin amyloidosis (hATTR) with polyneuropathy in adult patients
      • Commercially available in 15 countries
      • Secured pricing and reimbursement in multiple new EU markets and in Canada in the largest provinces and with multiple private payers
      • Won 2020 Prix Galien USA Award for the Best Biotechnology Product
    • WAYLIVRA: the only approved treatment in the EU for adults with genetically confirmed familial chylomicronemia syndrome (FCS) at high risk for pancreatitis
      • Commercially available in 4 countries
      • Finalized pricing negotiations in additional EU markets, including in the UK

    Third Quarter 2020 and Recent Pipeline Highlights

    • Positive Phase 2 vupanorsen and AKCEA-APOCIII-LRx results presented at the European Society of Cardiology annual meeting
    • Advanced multiple programs into key mid-stage studies
      • Vupanorsen advanced into Phase 2b development with the initiation of the TRANSLATE-TIMI 70 dose-ranging study in statin-treated patients with dyslipidemia, resulting in a $75 million payment from Pfizer
      • IONIS-FXI-LRx advanced into Phase 2b development in patients with end-stage renal disease
      • IONIS-HBVRx advanced into Phase 2b development in patients with hepatitis B virus infection
    • Advanced inhaled delivery
      • Positive IONIS-ENAC-2.5Rx healthy volunteer results provided support for inhaled antisense medicine delivery
      • Dosing completed in the IONIS-ENAC-2.5Rx Phase 2 study in patients with cystic fibrosis
    • Advanced the IONIS-PKK-LRx program
      • Proof-of-concept data from the PKK development program in patients with hereditary angioedema were reported in the New England Journal of Medicine
      • Enrollment completed in the IONIS-PKK-LRx Phase 2 study in patients with hereditary angioedema
      • IONIS-PKK-LRx advanced into an investigator-initiated study in hospitalized COVID-19 patients in Brazil
    • Progressed multiple neurological disease medicines under Ionis' broad collaboration with Biogen, earning more than $50 million
      • ION541 advanced into Phase 1/2 development in patients with nearly all forms of ALS
      • ION464 advanced into Phase 1/2 development in patients with multiple system atrophy
      • IONIS-MAPTRx continued to advance in a long-term extension study in patients with Alzheimer's disease 
    • The U.S. FDA granted orphan drug designation to Ionis-owned medicines for people with Alexander disease, β-thalassemia and Lafora diseases  

    Upcoming Catalysts 

    • Report clinical data, potentially enabling key programs to advance towards the market:
      • Subcutaneous and orally delivered ION449 targeting PCSK9 at the American Heart Association Scientific Sessions 2020
      • IONIS-AGT-LRx Phase 2 studies in patients with hypertension
      • IONIS-ENAC-2.5Rx Phase 2 study in patients with cystic fibrosis
      • IONIS-GHR-LRx Phase 2 study in patients with acromegaly
      • IONIS-PKK-LRx Phase 2 study in patients with hereditary angioedema
    • Advance the pipeline with numerous study initiations:
      • AKCEA-APOCIII-LRx Phase 3 study in patients with FCS
      • ION363 registrational study in patients with FUS-ALS
      • IONIS-ENAC-2.5Rx Phase 2 study in patients with chronic obstructive pulmonary disease
      • Phase 1/2 studies of Ionis-owned medicines:
        • ION251 for patients with multiple myeloma
        • ION373 for patients with Alexander disease
        • ION716 for patients with Prion diseases
    • Expand TEGSEDI and WAYLIVRA commercial availability in the EU and Latin America
    • Refile the WAYLIVRA application for marketing authorization in the U.S. next year

    Revenue

    Ionis' revenue was comprised of the following (amounts in millions):





    Three months ended,



    Nine months ended,





    September 30,



    September 30,





    2020



    2019



    2020



    2019

    Revenue:













         Commercial revenue:

















    SPINRAZA royalties



    $74



    $82



    $212



    $212

    Product sales, net



    19



    12



    51



    29

    Licensing and royalty revenue



    2



    2



    6



    11

    Total commercial revenue



    95



    96



    269



    252

    R&D Revenue:

















    Amortization from upfront payments



    19



    23



    68



    100

    Milestone payments



    44



    12



    73



    64

    License fees



    -



    26



    15



    198

    Other services



    2



    11



    14



    15

    Total R&D revenue



    65



    72



    170



    377

    Total revenue



    $160



    $168



    $439



    $629

    Operating Expenses

    Ionis' operating expenses for the third quarter of 2020 increased compared to the same period in 2019 driven by the Company's investments in advancing the Phase 3 program for AKCEA-TTR-LRx and other medicines in its Ionis-owned pipeline.  

    Net Loss Attributable to Noncontrolling Interest in Akcea

    Prior to completing its acquisition of Akcea in October 2020, Ionis owned approximately 76 percent of Akcea. The line titled "Net loss attributable to noncontrolling interest in Akcea" on Ionis' statement of operations reflects the portion of Akcea's net income or loss attributable to the other owners of Akcea's common stock. In October 2020, after the acquisition of Akcea closed, Ionis no longer recognizes any noncontrolling interest in Akcea on its statement of operations.  

    Net Income (Loss) Attributable to Ionis Common Stockholders

    Ionis recognized a net loss attributable to Ionis' common stockholders for the third quarter of 2020 compared to net income in the same period in 2019 primarily due to higher revenue in 2019, including a $150 million license fee Ionis earned from Novartis. Additionally, Ionis' operating expenses increased in 2020 compared to the same period last year as described above.

    Balance Sheet

    Ionis ended September 2020 with cash, cash equivalents and short-term investments of more than $2.3 billion, compared to $2.5 billion at December 31, 2019. In October 2020, Ionis used approximately $545 million of its cash for the Akcea acquisition.

    Webcast

    Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast to discuss this earnings release and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen) and WAYLIVRA (volanesorsen) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen. 

    IONIS PHARMACEUTICALS, INC.

    SELECTED FINANCIAL INFORMATION

    Condensed Consolidated Statements of Operations

    (In Millions, Except Per Share Data)







    Three months ended,



    Nine months ended,





    September 30,



    September 30,





    2020



    2019



    2020



    2019



















    (unaudited)

    Revenue:

















         Commercial revenue:

















    SPINRAZA royalties



    $74



    $82



    $212



    $212

    Product sales, net



    19



    12



    51



    29

    Licensing and royalty revenue



    2



    2



    6



    11

    Total commercial revenue



    95



    96



    269



    252

        Research and development revenue under

        collaborative agreements



    65



    72



    170



    377

    Total revenue



    160



    168



    439



    629

    Expenses:

















           Cost of products sold



    3



    1



    9



    3

        Research, development and patent



    125



    104



    364



    317

        Selling, general and administrative



    69



    60



    215



    204

    Total operating expenses



    197



    165



    588



    524



















    Income (loss) from operations



    (37)



    3



    (149)



    105



















    Other income (loss), net



    (3)



    1



    3



    4

    Income (loss) before income tax benefit (expense)



    (40)



    4



    (146)



    109





































    Income tax benefit (expense)



    (3)



    14



    1



    (10)



















    Net income (loss)



    $(43)



    $18



    $(145)



    $99

    Net loss attributable to noncontrolling interest in Akcea

    Therapeutics, Inc.



    12



    8



    34



    11

    Net income (loss) attributable to Ionis Pharmaceuticals,

    Inc. common stockholders



    $(31)



    $26



    $(111)



    $110



















    Basic net income (loss) per share



    $(0.22)



    $0.19



    $(0.80)



    $0.81

    Diluted net income (loss) per share



    $(0.22)



    $0.18



    $(0.80)



    $0.79

    Shares used in computing basic net income (loss) per share



    140



    141



    139



    140

    Shares used in computing diluted net income (loss) per share



    140



    143



    139



    143

     

    IONIS PHARMACEUTICALS, INC.

    SELECTED FINANCIAL INFORMATION

    Condensed Consolidating Statement of Operations

    (In Millions)









    Nine months ended,

    September 30, 2020

    (unaudited)





    Ionis



    Akcea



    Eliminations



    Ionis

    Consolidated



    Revenue:







         Commercial revenue:



















    SPINRAZA royalties



    $212



    $-



    $-



    $212



    Product sales, net



    -



    51



    -



    51



    Licensing and royalty revenue



    6



    -



    -



    6



    Total commercial revenue



    218



    51



    -



    269



        Research and development revenue under 

         collaborative agreements



    163



    7



    -



    170



        Intercompany revenue



    8



    -



    (8)



    -



    Total revenue



    389



    58



    (8)



    439



    Expenses:



















           Cost of products sold



    -



    16



    (7)



    9



        Research, development and patent expenses



    297



    72



    (5)



    364



        Selling, general and administrative



    88



    127



    -



    215



    Profit/ loss share for TEGSEDI

    commercialization activities



    12



    (12)



    -



    -



    Total operating expenses



    397



    203



    (12)



    588























    Loss from operations



    (8)



    (145)



    4



    (149)























    Other income, net



    -



    3



    -



    3



    Loss before income tax benefit



    (8)



    (142)



    4



    (146)























    Income tax benefit



    1



    -



    -



    1























    Net loss



    $(7)



    $(142)



    $4



    $(145)



    Net loss attributable to noncontrolling interest in

    Akcea Therapeutics, Inc.



    $-



    $-



    $34



    $34



    Net loss attributable to Ionis Pharmaceuticals, Inc.

    common stockholders



    $(7)



    $(142)



    $38



    $(111)

























     

    IONIS PHARMACEUTICALS, INC.

    Reconciliation of GAAP to Non-GAAP Basis:

    Condensed Consolidated Operating Expenses, Income (Loss) From Operations, and Net Income (Loss)

    (In Millions)







    Three months ended,

    September 30,



    Nine months ended,

    September 30,





    2020



    2019



    2020



    2019





    (unaudited)

    As reported research, development and patent

    expenses according to GAAP



    $125



    $104



    $364



    $317

        Excluding compensation expense related to equity awards      



    (25)



    (24)



    (77)



    (72)



















    Non-GAAP research, development and patent

    expenses



    $100



    $80



    $287



    $245



    As reported selling, general and administrative

    expenses according to GAAP



    $69



    $60



    $215



    $204

        Excluding compensation expense related to equity awards      



    (20)



    -



    (57)



    (39)



















    Non-GAAP selling, general and administrative

    expenses



    $49



    $60



    $158



    $165



    As reported operating expenses according to GAAP



    $197



    $165



    $588



    $524

        Excluding compensation expense related to equity awards      



    (46)



    (24)



    (135)



    (112)



















    Non-GAAP operating expenses



    $151



    $141



    $453



    $412



















    As reported income (loss) from operations according

    to GAAP



    $(37)



    $3



    $(149)



    $105

        Excluding compensation expense related to equity awards



    (46)



    (24)



    (135)



    (112)

    Non-GAAP income (loss) from operations



    $9



    $27



    $(14)



    $217

    As reported net income (loss) attributable to Ionis

    Pharmaceuticals, Inc. common stockholders

    according to GAAP



    $(31)



    $26



    $(111)



    $110

    Excluding compensation expense related to equity awards 

         attributable to Ionis Pharmaceuticals, Inc. common

          stockholders



    (42)



    (25)



    (126)



    (104)

    Income tax effect related to compensation expense related 

         to equity awards attributable to Ionis Pharmaceuticals,

          Inc. common stockholders



    6



    12



    18



    25

    Non-GAAP net income (loss) attributable to Ionis

    Pharmaceuticals, Inc. common stockholders

    according to GAAP



    $5



    $39



    $(3)



    $189

    Reconciliation of GAAP to Non-GAAP Basis

    As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (loss) attributable to Ionis Pharmaceuticals, Inc. common shareholders were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effect. Compensation expense related to equity awards are non-cash. Ionis has regularly reported non-GAAP measures for operating results as non-GAAP results. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations.

    IONIS PHARMACEUTICALS, INC.

    Condensed Consolidated Balance Sheets

    (In Millions)
     







    September 30,



    December 31,







    2020



    2019







    (unaudited)







    Assets:











      Cash, cash equivalents and short-term investments



    $2,329



    $2,500



      Contracts receivable



    39



    63



      Other current assets



    169



    158



      Property, plant and equipment, net



    182



    154



      Other assets



    377



    358



         Total assets



    $3,096



    $3,233















    Liabilities and stockholders' equity:











      Other current liabilities



    $140



    $155



      Current portion of deferred contract revenue



    105



    118



      0.125% convertible senior notes



    450



    435



      1% convertible senior notes



    289



    275



      Long-term obligations, less current portion



    76



    75



      Long-term deferred contract revenue



    430



    490



      Total Ionis stockholders' equity



    1,383



    1,471



      Noncontrolling interest in Akcea Therapeutics, Inc.



    223



    214



      Total stockholders' equity



    $1,606



    $1,685



        Total liabilities and stockholders' equity



    $3,096



    $3,233

















     

    IONIS PHARMACEUTICALS, INC.

    Condensed Consolidating Balance Sheet

    (In Millions)







    September 30, 2020

    (unaudited)

















    Ionis





    Ionis



    Akcea



    Eliminations



    Consolidated



















    Assets:

















      Cash, cash equivalents and short-term investments



    $1,963



    $366



    $-



    $2,329

      Contracts receivable



    23



    16



    -



    39

      Other current assets



    150



    28



    (9)



    169

      Property, plant and equipment, net



    176



    6



    -



    182

      Other assets



    1,125



    92



    (840)



    377

         Total assets



    $3,437



    $508



    $(849)



    $3,096



















    Liabilities and stockholders' equity:

















      Other current liabilities



    100



    49



    (9)



    140

      Current portion of deferred contract revenue



    105



    -



    -



    105

      0.125% convertible senior notes



    450



    -



    -



    450

      1% convertible senior notes



    289



    -



    -



    289

      Long-term obligations, less current portion



    62



    14



    -



    76

      Long-term deferred contract revenue



    432



    -



    (2)



    430

      Total stockholders' equity before noncontrolling interest



    1,999



    445



    (1,061)



    1,383

      Noncontrolling interest in Akcea Therapeutics, Inc.



    -



    -



    223



    223

      Total stockholders' equity



    $1,999



    $445



    $(838)



    $1,606

         Total liabilities and stockholders' equity



    $3,437



    $508



    $(849)



    $3,096

     

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  17. CARLSBAD, Calif. and BOSTON, Nov. 3, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) and its wholly owned subsidiary Akcea Therapeutics, Inc., today announced that Pfizer Inc. (NYSE:PFE) has initiated a Phase 2b study of vupanorsen (AKCEA-ANGPTL3-LRx) in statin-treated patients with elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs). The study, Targeting ANGPTL3 with an antisense oligonucleotide in adults with dyslipidemia (TRANSLATE-TIMI 70), will evaluate various doses of vupanorsen to inform potential future development.

    In the Phase 2a study, vupanorsen met the primary endpoint of significant reductions in TG levels and multiple secondary endpoints compared to placebo, with a favorable safety…

    CARLSBAD, Calif. and BOSTON, Nov. 3, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) and its wholly owned subsidiary Akcea Therapeutics, Inc., today announced that Pfizer Inc. (NYSE:PFE) has initiated a Phase 2b study of vupanorsen (AKCEA-ANGPTL3-LRx) in statin-treated patients with elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs). The study, Targeting ANGPTL3 with an antisense oligonucleotide in adults with dyslipidemia (TRANSLATE-TIMI 70), will evaluate various doses of vupanorsen to inform potential future development.

    In the Phase 2a study, vupanorsen met the primary endpoint of significant reductions in TG levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability profile.

    "Results from the Phase 2a study recently presented at the ESC Congress and published in the European Heart Journal, showed that antisense-mediated reduction of ANGPTL3 has the potential to address unmet needs in patients with atherosclerotic cardiovascular diseases, and adds to the growing body of evidence supporting our LICA antisense technology," said Sam Tsimikas, vice president of global cardiovascular development at Ionis. "We look forward to seeing Pfizer advance the Phase 2b study and report results on this clinical program."

    The first patient has been treated in the multicenter, double-blind, placebo-controlled, dose-ranging Phase 2b study. TRANSLATE-TIMI 70 has an estimated total enrollment of 260 participants (≥ 40 years old) with elevated non-HDL-C (≥ 100 mg/dL) and triglycerides (150-500 mg/dL) who are receiving a stable dose of a statin. The study will explore different doses and dose regimens versus placebo, with patients receiving either 80 mg, 120 mg or 160 mg every 4 weeks, or 60 mg, 80 mg, 120 mg or 160 mg every two weeks via subcutaneous injection. The study (NCT04516291) will assess the efficacy, safety, tolerability and pharmacokinetics of vupanorsen, and the primary endpoint is percent change from baseline in non-HDL-C at week 24.

    In November 2019, Akcea and Ionis announced the closing of a worldwide exclusive licensing agreement with Pfizer for vupanorsen. Pfizer is responsible for all development and regulatory activities and costs for vupanorsen beyond those associated with the Phase 2a study. Under the terms of the licensing agreement, the initiation of the Phase 2b study triggered a milestone payment of $75 million from Pfizer.

    ABOUT VUPANORSEN

    Vupanorsen is an investigational antisense therapy being developed for potential indications in cardiovascular risk reduction and severe hypertriglyceridemia. Vupanorsen is designed to reduce the production of angiopoietin-like 3 (ANGPTL3) protein, a key regulator of triglyceride and cholesterol metabolism, in the liver. This antisense therapy was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery that people with a genetic deficiency in ANGPTL3 have reduced levels of low-density lipoprotein cholesterol (LDL-C) and TG, and a decreased risk of diabetes and cardiovascular disease.1 In a Phase 1 study, subjects treated with vupanorsen achieved robust, dose-dependent reductions in ANGPTL3, TG, LDL-C, non-HDL-C and total cholesterol with a favorable safety and tolerability profile.2  In a Phase 2a study, vupanorsen met the primary endpoint of significant reductions in TG levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability profile.

    Vupanorsen was discovered by Ionis and has been co-developed by Akcea and Ionis. In November 2019, Akcea and Ionis announced the closing of a worldwide exclusive licensing agreement with Pfizer Inc. for vupanorsen. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the Phase 2a study.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    ABOUT AKCEA THERAPEUTICS

    Akcea Therapeutics, Inc. is a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in RNA therapeutics.  Akcea commercializes TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), and with Ionis, is advancing a mature pipeline of novel medicines discovered by Ionis and based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. For more information about Akcea, please visit www.akceatx.com.

    FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of vupanorsen (AKCEA-ANGPTL3-LRx) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    References

    1. JAMA Cardiol. 2018 Oct 1;3(10):957-966.
    2. N Engl J Med. 2017 Jul 20;377(3):222-232.

     

    (PRNewsfoto/Akcea Therapeutics, Inc.)

    (PRNewsfoto/Ionis Pharmaceuticals, Inc.,Akc)

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  18. BOSTON and CARLSBAD, Calif., Oct. 30, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) and its wholly owned subsidiary, Akcea Therapeutics, received the Prix Galien USA Award for the Best Biotechnology Product in 2020 in recognition of TEGSEDI, the first and only self-administered, subcutaneous treatment for the polyneuropathy of hereditary ATTR amyloidosis in adults. This Prix Galien award recognizes outstanding achievements in biomedicine that improve the human condition and was presented at a virtual ceremony on Thursday, Oct. 29.

    "We are thrilled to accept this award for TEGSEDI – a treatment that has already provided substantial benefit  for those who have been devastated with the polyneuropathy associated with  hereditary transthyretin amyloidosis," said Brett P. Monia, Ph.D., chief executive  officer at Ionis, and a founding scientist at Ionis who led the discovery and development of TEGSEDI. "Our vision in the discovery and development of TEGSEDI was to improve the lives of patients living with the devastating effects of this rare genetic disease that impacts the lives of generations of families. I would like to thank our teams at Akcea and Ionis for their tireless work and dedication in developing TEGSEDI and giving hope to patients worldwide."

    The international Prix Galien Award is presented annually by the Galien Foundation. The Prix Galien USA Committee comprises renowned leaders from the biomedical industry and academia, who together are responsible for evaluating nominees. To qualify, each candidate must be U.S. Food and Drug Administration-approved for marketing within the last five years and demonstrate significant potential to advance human health worldwide. Since its inception in 1970, the Prix Galien is considered the biopharmaceutical and medical industries' equivalent of the Nobel prize.

    ABOUT HEREDITARY TRANSTHYRETIN (hATTR) AMYLOIDOSIS 

    Hereditary ATTR amyloidosis is a severe, progressive, and life-threatening disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, the heart and intestinal tract. The progressive accumulation of TTR amyloid deposits in these organs often leads to intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. Hereditary ATTR amyloidosis causes significant morbidity and progressive decline in quality of life, severely impacting activities of daily living. The disease often progresses rapidly and can lead to premature death. The median survival is 4.7 years following diagnosis. Additional information on hereditary ATTR amyloidosis, including a full list of organizations supporting the hATTR amyloidosis community worldwide, is available at www.hattrchangethecourse.com or by visiting www.hATTRGuide.com.

    ABOUT TEGSEDI®(INOTERSEN) 

    TEGSEDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. TEGSEDI, discovered and developed by Ionis Pharmaceuticals, is the world's first and only subcutaneous RNA-targeting drug designed to reduce the production of human transthyretin (TTR) protein. TEGSEDI also received marketing authorization in the European Union and Canada for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis. 

    The approval is based on data from the NEURO-TTR study that was a Phase 3 randomized (2:1), double-blind, placebo-controlled, 15-month, international study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, TEGSEDI demonstrated significant improvement compared to placebo in measures of neuropathy and quality of life as measured by the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. Patients treated with TEGSEDI experienced similar benefit regardless of subgroups such as age, sex, race, region, Neuropathy Impairment Score (NIS), Val30Met mutation status, and disease stage. 

    The approval is also based on data from the NEURO-TTR Open Label Extension (OLE) that is an ongoing study for patients who completed the NEURO-TTR study, designed to evaluate the long-term efficacy and safety of TEGSEDI. 

    For TEGSEDI's full prescribing information, please visit www.TEGSEDI.com

    About Akcea Therapeutics, Inc.

    Akcea Therapeutics, Inc., is a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in RNA therapeutics.  Akcea commercializes TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), and with Ionis is advancing a mature pipeline of novel medicines discovered by Ionis and based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. For more information about Akcea please visit www.akceatx.com.

    ABOUT IONIS PHARMACEUTICALS, INC. 

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma. 

    FORWARD-LOOKING STATEMENT 

    This press release includes forward-looking statements regarding the therapeutic and commercial potential of TEGSEDI (inotersen) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® TEGSEDI® are trademarks of Akcea Therapeutics, Inc. 

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    SOURCE Akcea Therapeutics, Inc.; Ionis Pharmaceuticals, Inc.

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  19. CARLSBAD, Calif., Oct. 22, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, today announced that the first patients have been dosed with ION541 (also known as BIIB105), an investigational antisense medicine being developed as a potential therapy to treat most forms of amyotrophic lateral sclerosis (ALS) regardless of family history. This is another milestone in the continuing progress of Ionis' ambitious program to develop novel treatments for ALS. Almost all cases of ALS share the pathological hallmark of TDP-43 protein aggregation in motor neurons. ION541 targets ataxin-2 RNA (ATXN2), which has been shown to prevent or reverse TDP-43 toxicity in preclinical models of ALS.

    CARLSBAD, Calif., Oct. 22, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, today announced that the first patients have been dosed with ION541 (also known as BIIB105), an investigational antisense medicine being developed as a potential therapy to treat most forms of amyotrophic lateral sclerosis (ALS) regardless of family history. This is another milestone in the continuing progress of Ionis' ambitious program to develop novel treatments for ALS. Almost all cases of ALS share the pathological hallmark of TDP-43 protein aggregation in motor neurons. ION541 targets ataxin-2 RNA (ATXN2), which has been shown to prevent or reverse TDP-43 toxicity in preclinical models of ALS.

    ALS is a rare, progressive and fatal neurodegenerative disorder that affects approximately 55,000 people globally.i  About 90 percent of ALS cases occur in people who have no apparent family history of the disease. People with ALS experience muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and potentially death.

    "As our third medicine designed to treat different forms of ALS to enter clinical trials, ION541 represents yet another example of the power of Ionis' antisense technology to potentially target root causes of devastating neurodegenerative diseases," said Frank Bennett, Ph.D., Ionis' chief scientific officer and franchise leader for neurological programs. "Initiation of this clinical trial for ION541 marks an important milestone in Ionis' ALS program and reaffirms our commitment to the ALS community."

    Ionis received a payment of $10 million from Biogen for initiation of this Phase 1/2 clinical trial of ION541. Biogen is developing ION541 as part of a broad strategic collaboration with Ionis to advance novel antisense therapies for the treatment of neurological disorders.

    Learn more about the Phase 1/2 trial of ION541 at: https://clinicaltrials.gov/ct2/show/NCT04494256?term=biib105&draw=2&rank=1

    Ionis' other leading investigational medicines to treat ALS are tofersen (BIIB067) and IONIS-C9Rx (BIIB078), both partnered with Biogen. Tofersen is designed to reduce the production of superoxide dismutase 1 (SOD1), the cause of a genetic form of ALS, referred to as SOD1-ALS, that results from mutations in the SOD1 gene. SOD1-ALS is the second most common genetic form of ALS, accounting for up to 20 percent of genetic ALS. Tofersen is currently in a Phase 3 clinical trial in SOD1-ALS patients with data expected in 2021. IONIS-C9Rx is designed to selectively reduce the mutant C9ORF72 RNA and associated neurotoxicity. Mutations in the C9orf72 gene account for greater than 30 percent of genetic ALS cases and five to 10 percent of all patients with ALS. It is the most common genetic form of ALS worldwide. IONIS-C9Rx is the first drug to enter clinical development that specifically targets the mutant C9ORF72 RNA and is a potentially first-in-class therapy for patients with C9orf72-ALS, referred to as C9-ALS. IONIS-C9Rx, which earlier this year received Fast Track designation from the U.S. Food and Drug Administration, is currently in a Phase 1/2 trial in C9-ALS patients.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic potential of ION541, tofersen and IONIS-C9Rx. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    i G7 countries: Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  20. CARLSBAD, Calif., Oct. 21, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that it will host a live webcast on Wednesday, November 4th at 11:30 a.m. Eastern Time to discuss its third quarter 2020 financial results and report on pipeline and business progress.

    Interested parties may access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardiovascular, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  21. CARLSBAD, Calif., Oct. 15, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced  today that IONIS-PKK-LRx is being evaluated in an investigator-initiated Phase 2 clinical study to determine its effectiveness in reducing the severity of respiratory complications in patients with COVID-19. The trial coordinators are Fernando G. Zampieri, M.D., Ph.D., and Alexandre Biasi Cavalcanti, M.D., Hospital do Coracao (HCor Research Institute), Sao Paulo, Brazil. The study will enroll up to 110 patients at 25 hospitals in Brazil. Ionis has provided IONIS-PKK-LRx and funding to the Brazilian Research for Intensive Care Network (BRICNet) to support the study.

    CARLSBAD, Calif., Oct. 15, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced  today that IONIS-PKK-LRx is being evaluated in an investigator-initiated Phase 2 clinical study to determine its effectiveness in reducing the severity of respiratory complications in patients with COVID-19. The trial coordinators are Fernando G. Zampieri, M.D., Ph.D., and Alexandre Biasi Cavalcanti, M.D., Hospital do Coracao (HCor Research Institute), Sao Paulo, Brazil. The study will enroll up to 110 patients at 25 hospitals in Brazil. Ionis has provided IONIS-PKK-LRx and funding to the Brazilian Research for Intensive Care Network (BRICNet) to support the study.

    IONIS-PKK-LRx is designed to inhibit bradykinin signaling by halting synthesis of prekallikrein (PKK), a precursor of the enzyme kallikrein, which is involved in the formation of bradykinin, a protein that promotes inflammation and dilates blood vessels. There is growing evidence that the pulmonary edema (fluid in the lungs) and associated morbidities in severe COVID-19, such as the respiratory distress syndrome, are, in part, caused by a dysregulation in bradykinin signaling, referred to as a "bradykinin storm". A therapy that prevents or reduces this bradykinin storm could potentially decrease the number of severe cases of COVID-19 in Brazil.

    "Bradykinin elevations in the body can cause blood vessels to become leaky, causing inflammation in the surrounding tissue. In the lungs, this is often associated with severe COVID-19 cases. We are hopeful that IONIS-PKK-LRx can alleviate some of the worst symptoms caused by the infection and we look forward to seeing data from the study," said Kenneth Newman, M.D., M.B.A., Ionis' vice president of clinical development and leader of the pulmonology and immunology franchise.

    In the study, a single dose of IONIS-PKK-LRx or placebo will be administered subcutaneously to hospital patients who present with symptoms consistent with COVID-19. The primary endpoint is the number of days alive and free of oxygen support up to 15 days.

    Learn more about the Phase 2 study here: Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19 (ASKCOV).

    IONIS-PKK-LRx is also undergoing a Phase 2 clinical study in patients with hereditary angioedema (HAE). In September, the New England Journal of Medicine published encouraging data showing safety and efficacy in two patients with uncontrolled, severe HAE. These data support the continued development of IONIS-PKK-LRx as a potential treatment in patients with severe HAE for whom current therapies offer limited therapeutic benefit.

    IONIS-PKK-LRx is one of 20 potentially transformative antisense programs in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization.

    About IONIS-PKK-LRx

    IONIS-PKK-LRx is an investigational antisense medicine designed to reduce the production of prekallikrein, or PKK, in patients with hereditary angioedema, or HAE, a rare, genetic, potentially fatal disease characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea. IONIS-PKK-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. Current prophylactic treatment approaches are limited and have major tolerability issues, leaving patients with few therapeutic options. IONIS-PKK-LRx is also undergoing an investigator-initiated Phase 2 clinical study in Brazil to evaluate its effectiveness in reducing the severity of respiratory complications in patients with COVID-19.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic potential of IONIS-PKK-LRx. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

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  22. CARLSBAD, Calif., Oct. 13, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced today that data from a clinical trial of IONIS-ENAC-2.5Rx demonstrated a significant decrease in the expression of epithelial sodium channel (ENaC) in subjects with cystic fibrosis (CF). The study showed a mean 55.6 percent decrease (p<0.05) in ENaC mRNA expression at the 75 mg dose in the multidose segment of the trial. The study represents the first time an antisense medicine delivered directly to the lung via a nebulizer has shown a significant reduction in ENaC messenger RNA levels. In preclinical studies, ENaC mRNA reductions of 40 percent or more resulted in significant improvement in mouse models of CF lung disease.

    IONIS-ENAC-2.5Rx is an investigational antisense medicine designed to reduce the expression of ENaC in the lung. ENaC is believed to be hyperactive in cystic fibrosis, which is caused by mutations in the cystic fibrosis transmembrane regulator gene. Data from the Phase 1 study will be presented via e-poster at the 2020 North American Cystic Fibrosis Conference, which will hold virtual sessions and discussions Oct. 21-23.

    Cystic fibrosis is a life-threatening disease affecting approximately 30,000 people in the U.S. and about 70,000 worldwide. Although CF is a multisystem disease, the main cause of morbidity and mortality is lung disease, characterized by small airway obstruction due to mucus accumulation, decreased mucus clearing and subsequent inflammation, infections and lung function decline.

    "We are very encouraged by these data, which demonstrate attractive tolerability and safety for IONIS-ENAC-2.5Rx with substantial target reduction and the convenience of once weekly administration. The data also confirm our expectations for aerosol delivery of antisense medicines for lung diseases based on a wealth of preclinical data," said Brett P. Monia, Ph.D., Ionis' chief executive officer. "These results point to the exciting potential for aerosol delivery of other Ionis medicines that we plan to advance to the clinic, including treatments for chronic obstructive pulmonary disease, or COPD, and severe asthma."

    The company also plans to initiate a clinical study to evaluate IONIS-ENAC-2.5Rx in patients with COPD associated with chronic bronchitis starting later this year. IONIS-ENAC-2.5Rx is one of more than 20 potentially transformative antisense medicines in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization.

    The primary endpoint of the study was evaluation of safety and pharmacokinetics of IONIS-ENAC-2.5Rx delivered via a Pari eFlow mesh nebulizer. In the single escalating dose study, 32 subjects in four cohorts received a single dose of 3, 10, 37.5, or 100 mg and were followed for 30 days. In the multiple ascending dose study, 24 subjects in three cohorts received four doses of 10, 37.5, or 75 mg once weekly, with an additional dose administered during the first week. An additional cohort of eight subjects received a 37.5 mg dose given thrice weekly for 10 doses. Subjects were followed for 13 weeks after dosing. Fiberoptic bronchoscopy including bronchial brushings and bronchoalveolar lavage was performed during screening and after completion of dosing in the MAD cohorts. Quantitative RT-PCR was performed from the bronchial cell brushings to evaluate ENaC mRNA levels.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of IONIS-ENAC-2.5Rx and Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

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  23. CARLSBAD, Calif., Oct. 12, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced the successful completion of its transaction to acquire 100% ownership of Akcea Therapeutics, Inc. (NASDAQ:AKCA). The combination of Ionis and Akcea accelerates the next phase of Ionis' growth and positions it to better deliver more medicines to patients while maximizing value to all stakeholders. Under the terms of the definitive agreement, Akcea shareholders will receive $18.15 in cash for each share of Akcea common stock. As a result of the completion of the transaction, Akcea has become a wholly owned subsidiary of Ionis, and the common stock of Akcea will cease to trade on NASDAQ and be delisted.

    CARLSBAD, Calif., Oct. 12, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today announced the successful completion of its transaction to acquire 100% ownership of Akcea Therapeutics, Inc. (NASDAQ:AKCA). The combination of Ionis and Akcea accelerates the next phase of Ionis' growth and positions it to better deliver more medicines to patients while maximizing value to all stakeholders. Under the terms of the definitive agreement, Akcea shareholders will receive $18.15 in cash for each share of Akcea common stock. As a result of the completion of the transaction, Akcea has become a wholly owned subsidiary of Ionis, and the common stock of Akcea will cease to trade on NASDAQ and be delisted.

    TRANSACTION DETAILS

    On September 14, 2020, Avalanche Merger Sub, Inc., a wholly-owned subsidiary of Ionis, commenced a tender offer to acquire all of the outstanding shares of Akcea at a price of $18.15 per share in cash, without interest and subject to withholding of taxes. The tender offer expired at one minute after 11:59 p.m., Eastern Time, on October 9, 2020 and was not extended. Ionis accepted for payment all shares tendered and not validly withdrawn in the offer and will promptly pay for such shares, which represented approximately 85.5% of the outstanding shares of Akcea's common stock not already owned by Ionis.

    After the completion of the tender offer, Avalanche Merger Sub merged with and into Akcea on October 12, 2020, with Akcea surviving as a wholly owned subsidiary of Ionis.  All shares of Akcea not held by Ionis, Akcea, any wholly owned subsidiary of Ionis, or stockholders of Akcea who have perfected their statutory appraisal rights under Delaware law, were converted into the right to receive $18.15 per share in cash, as was paid in the tender offer.

    ADVISORS

    Goldman Sachs & Co. LLC and Stifel, Nicolaus, & Company, Incorporated served as financial advisors to Ionis, and Skadden, Arps, Slate, Meagher & Flom LLP served as legal counsel to Ionis. Cowen served as financial advisor to the Affiliate Transactions Committee of Akcea's Board of Directors, and Ropes & Gray LLP served as legal counsel to the Affiliate Transactions Committee of Akcea's Board of Directors.

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    FORWARD-LOOKING STATEMENTS

    Ionis Pharmaceuticals, Inc. assumes no obligation to update forward-looking statements contained in this communication as a result of new information or future events or developments except as required by law. This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc., the therapeutic and commercial potential of TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen) and the acquisition of Akcea by Ionis that are subject to risks and uncertainties that could cause actual results to differ materially from those expressly or implied by such statements. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of TEGSEDI and WAYLIVRA or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Risks and uncertainties also include, among other things, disruption from the transaction making it more difficult to maintain business and operational relationships; risks that anticipated synergies will not be realized or may be delayed; and the magnitude of transaction costs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from the company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company,"  "we," "our," and "us" refers to Ionis Pharmaceuticals or Akcea Therapeutics, as applicable.

    Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

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  24. CARLSBAD, Calif., Oct. 1, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced today that Frank Bennett, Ph.D., Ionis' executive vice president and chief scientific officer, has been awarded the 2020 Lifetime Achievement Award by the Oligonucleotide Therapeutics Society (OTS). Dr. Bennett was recognized by the OTS Award Committee for his important contributions to basic science and for being instrumental in the development of antisense oligonucleotide drugs that modulate splicing to correct severe genetic disease.

    A founding member of Ionis, Dr. Bennett is responsible for continuing to advance antisense technology and expanding Ionis' drug discovery platform. He is also the franchise leader for neurological programs at Ionis. Dr. Bennett is a co-recipient of the 2019 Breakthrough Prize in Life Sciences for his contributions to the discovery and development of SPINRAZA® (nusinersen) and a co-recipient of the inaugural Healy Center International Prize for Innovation in amyotrophic lateral sclerosis (ALS). Dr. Bennett also received the 2018 Hereditary Disease Foundation's (HDF) Leslie Gehry Brenner Prize for Innovation in Science for his leadership and continued commitment to developing antisense therapies for Huntington's disease. He has been involved in the development of antisense oligonucleotides as therapeutic agents, including research on the application of oligonucleotides for inflammatory, neurodegenerative diseases and cancer, oligonucleotide delivery, pharmacokinetics and medicinal chemistry.

    "I am deeply honored and humbled to be recognized by the Oligonucleotide Therapeutics Society with the Lifetime Achievement Award. It represents an affirmation, not for me as an individual, but for everyone at Ionis who is committed to advancing science and to delivering transformative medicines to the patients who depend on us," said Dr. Bennett.

    Dr. Bennett will deliver his award lecture at the OTS 2021 meeting.

    OTS also recognized research by Ionis scientists with the Paper of the Year Award. Frank Rigo, Ph.D., vice president, functional genomics and drug discovery, Sagar Damle, Ph.D., director, functional genomics and Karen Ling, research fellow, neuroscience drug discovery, were the authors of Directed RNase H cleavage of nascent transcripts causes transcription termination, which uncovers a new antisense mechanism and highlights Ionis' commitment to remain leaders in RNA-targeted therapeutics.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

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  25. BOSTON and CARLSBAD, Calif., Oct. 1, 2020 /PRNewswire/ -- Genuity Science, a genomics and data insights organization and Ionis Pharmaceuticals (NASDAQ:IONS), the leader in antisense therapeutics, today announced a broad, multi-year collaboration aimed at accelerating the discovery and development of innovative therapeutics across a range of up to 20 diseases. The collaboration is expected to play an important role in allowing Ionis to continue delivering transformational medicines to patients for many years to come.

    Genuity Science's approach combines high-quality, whole-genome sequence and deep phenotype data resulting in better definition of the underlying disease mechanisms. This approach, when coupled with Ionis' proprietary antisense technology, has the potential to significantly expedite the drug development process through a more direct translation of targets into therapeutics.

    Under terms of the multi-year collaboration, Genuity Science will receive a combination of upfront payments and development milestones, plus product royalties.  

    "Ionis' financial strength and the success of our validated antisense technology have positioned us to invest in new technologies that enhance our R&D capabilities," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "The collaboration with Genuity Science gives us the potential to significantly increase our discovery opportunities and better understand the complexities of human diseases based on genetics."

    "We are excited to collaborate with an innovative company like Ionis," said Rob Brainin, chief executive officer of Genuity Science. "Combining the scale and depth of our datasets and our analytical expertise with Ionis' pioneering antisense technology can more rapidly translate information into insights with potential to deliver breakthrough therapies to even more patients who need them."

    Learn more by visiting https://contact.genuitysci.com/ionis.

    About Genuity Science

    Genuity Science is a data sourcing, analytics and insights organization headquartered in Boston, Massachusetts, USA, with offices in Dublin, Ireland and Reykjavik, Iceland. Genuity Science partners with global biopharma companies to offer deep end-to-end discovery services aimed at catalyzing precision health and improving the quality of life for patients around the world. Services include population-scale, disease-specific data sourcing, high-quality sequencing, robust statistical analysis and software tools for analyzing large datasets and artificial intelligence (AI). The company operates advanced CAP-accredited, CLIA-certified genomics laboratories in Woburn, Massachusetts, USA and in Dublin, Ireland and is deeply committed to data stewardship and data governance across its global offices. For more information, see www.genuitysci.com.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardiovascular, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' collaboration with Genuity Science. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, which is on file with the SEC. Copies of this and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

     

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  26. CARLSBAD, Calif., Sept. 30, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ION373 for the treatment of people with Alexander disease, a severe, progressive and debilitating rare neurodegenerative disease that can result in death. Infants and young children who develop the condition rarely survive beyond their teenage years or young adulthood. Alexander disease has been estimated to occur in about one in one million births. Orphan drug designation is granted by the FDA to drugs and biologics intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer…

    CARLSBAD, Calif., Sept. 30, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ION373 for the treatment of people with Alexander disease, a severe, progressive and debilitating rare neurodegenerative disease that can result in death. Infants and young children who develop the condition rarely survive beyond their teenage years or young adulthood. Alexander disease has been estimated to occur in about one in one million births. Orphan drug designation is granted by the FDA to drugs and biologics intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation.

    Alexander disease is caused by a mutation in a protein resulting in overproduction of glial fibrillary acidic protein (GFAP) in the brain. ION373 is an Ionis-owned investigational antisense medicine designed to stop the mutated gene from producing excess GFAP.

    Under the FDA's Orphan Drug Act, orphan drug status provides incentives, including waiver of certain administrative fees, grants and tax credits for clinical trials, and seven years of market exclusivity following drug approval. Earlier this year, the European Medicines Agency (EMA) granted orphan drug designation to ION373. EMA provides regulatory, financial and market incentives to develop therapies for life threatening or chronically debilitating conditions affecting not more than five in 10,000 people in the European Union (EU) and for which there is no satisfactory method of diagnosis, prevention or treatment.

    "Receiving FDA orphan drug status for ION373 reflects the urgent need for a novel medicine to treat Alexander disease. We look forward to working closely with regulators, clinical investigators, Alexander disease patients and their families to advance this important medicine and make it available to those who need it," said Frank Bennett, Ph.D., Ionis' chief scientific officer and franchise leader for neurological programs.

    ION373 is one of several Ionis-owned investigational medicines designed to treat neurological diseases. Others include ION716 (Prion disease), ION283 (Lafora disease) and ION363 (amyotrophic lateral sclerosis or ALS).

    About Alexander disease

    Alexander disease (AxD) is a rare neurological condition characterized as a leukodystrophy, or a disease affecting the myelin sheath (the fatty insulation that protects a nerve fiber and supports signal conduction). Two major types of AxD have been defined. Type I onset typically occurs before 4 years of age and patients can experience head enlargement, seizures, limb stiffness, delayed or declining cognition, and lack of growth. Type II onset typically occurs after the age of 4 and symptoms can include difficulty speaking, swallowing, and making coordinated movements. AxD is most often fatal. There are treatments that can relieve symptoms, but there is no disease modifying therapy yet available to patients.

    About Ionis Pharmaceuticals, Inc.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy, as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of ION373 and Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

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  27. CARLSBAD, Calif., Sept. 3, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), the leader in antisense therapeutics, today announced that management will present a company overview at the following virtual investor conferences:

    • Wells Fargo 2020 Healthcare Conference on Thursday, September 10, 2020;
    • Morgan Stanley 18th Annual Global Healthcare Conference on Monday, September 14, 2020;
    • BofA Global Healthcare Conference on Friday, September 18, 2020; and
    • Oppenheimer Fall Healthcare Life Sciences & MedTech Summit on Tuesday, September 22, 2020.

    The above listed dates are subject to change. Details on presentation times or changes to presentation dates can be found on the Company's website. Please check www.ionispharma.com for the latest information.

    A live webcast of the presentations will be available on the Investors & Media section of the Ionis website. The replays will be available within 48 hours and will be archived for a limited time.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

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  28. CARLSBAD, Calif., Sept. 2, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced the publication today of the results from a compassionate-use study evaluating IONIS-PKKRx and IONIS-PKK-LRx in patients living with severe bradykinin-mediated angioedema in The New England Journal of Medicine (NEJM). IONIS-PKKRx and IONIS-PKK-LRx are investigational antisense medicines designed to reduce the production of prekallikrein, or PKK, which plays a key role in the activation of inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). In the study, researchers found that the drugs reduced plasma prekallikrein activity levels and showed evidence of clinical efficacy in reducing the number of breakthrough attacks…

    CARLSBAD, Calif., Sept. 2, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced the publication today of the results from a compassionate-use study evaluating IONIS-PKKRx and IONIS-PKK-LRx in patients living with severe bradykinin-mediated angioedema in The New England Journal of Medicine (NEJM). IONIS-PKKRx and IONIS-PKK-LRx are investigational antisense medicines designed to reduce the production of prekallikrein, or PKK, which plays a key role in the activation of inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). In the study, researchers found that the drugs reduced plasma prekallikrein activity levels and showed evidence of clinical efficacy in reducing the number of breakthrough attacks per month in patients over the course of the treatment, including complete resolution in a patient with Type 1 HAE. To view the published study, please visit NEJM.org.

    Hereditary angioedema is a rare autosomal dominant disease that results in recurrent, painful attacks of swelling affecting the arms, legs, face, intestinal track and airway. Without preventive treatment, attacks can be frequent and severe and, in some patients, life-threatening. The majority of HAE cases are caused by genetic mutations that lead to either a deficiency (Type 1 HAE) or dysfunction (Type 2 HAE) of C1 esterase inhibitor (C1-INH), which regulates multiple pathways, including the kallikrein-kinin and contact system. In the third, especially rare form of the disorder (Type 3 HAE or HAE-nC1-INH), which occurs predominantly in women, and in which the cause is often unknown, patients have a higher frequency of facial, pharyngeal and tongue swelling.

    "The results of this study are encouraging and support continued development of IONIS-PKK-LRx as a potential treatment in patients with severe hereditary angioedema for whom current therapies offer limited therapeutic benefit. The study also highlights the progress we continue to make advancing investigational medicines that are wholly owned by Ionis," said Richard S. Geary, Ph.D., Ionis' executive vice president of Development and a co-author on the paper published in NEJM.

    In the study, two patients – Patient 1 with Type 1 HAE and Patient 2 with Type 3 HAE – were first treated with IONIS-PKKRx for a period of 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every three to four weeks for seven to eight months at the time of data analysis. During treatment with the ligand-conjugated IONIS-PKK-LRx and the unconjugated parent drug, IONIS-PKKRx, there was a clinically meaningful reduction in HAE attack rates in both patients. Plasma prekallikrein activity levels decreased substantially following treatment.

    Physicians have long prescribed prophylactic treatment approaches, including C1-INH replacement therapies and more recently inhibitors of plasma kallikrein, to prevent and reduce the severity of HAE attacks. IONIS-PKK-LRx is an investigational antisense medicine that is being developed because it has the potential to provide significant efficacy with the convenience of once per month low volume subcutaneous injections.

    Ionis' Forward-looking Statement

    This press release includes forward-looking statements regarding Ionis' business and the therapeutic potential of IONIS-PKK-LRx, IONIS-PKKRx and Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

    In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  29. CARLSBAD, Calif. and BOSTON, Aug. 31, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) and its affiliate Akcea Therapeutics, Inc. (NASDAQ:AKCA) today announced that they have entered into a definitive agreement under which Ionis will acquire all of the outstanding shares of Akcea common stock it does not already own, approximately 24%, for $18.15 per share in cash. This corresponds to a total transaction value of approximately $500 million on a fully diluted basis. The transaction has been approved by the Ionis and Akcea Boards of Directors, and by the independent Affiliate Transactions Committee of Akcea's Board of Directors. Akcea's Board of Directors has recommended to shareholders of Akcea that they tender their shares into…

    CARLSBAD, Calif. and BOSTON, Aug. 31, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) and its affiliate Akcea Therapeutics, Inc. (NASDAQ:AKCA) today announced that they have entered into a definitive agreement under which Ionis will acquire all of the outstanding shares of Akcea common stock it does not already own, approximately 24%, for $18.15 per share in cash. This corresponds to a total transaction value of approximately $500 million on a fully diluted basis. The transaction has been approved by the Ionis and Akcea Boards of Directors, and by the independent Affiliate Transactions Committee of Akcea's Board of Directors. Akcea's Board of Directors has recommended to shareholders of Akcea that they tender their shares into the tender offer.

    "This acquisition is another step forward in Ionis' evolution and creates a stronger, more efficient organization to the benefit of all stakeholders," said Brett Monia, Chief Executive Officer of Ionis. "We believe becoming one company – with one vision and one set of strategic priorities, led by one team – will deliver significant strategic value, enhancing the future success of our company, accelerating our next phase of growth and positioning us to most effectively deliver our medicines to patients. Following the completion of the transaction, Ionis will retain more value from Akcea's rich pipeline and commercial products, further strengthening our financial position and supporting continued investments in our future." 

    "Akcea values the skills, experience and expertise of our teams and I am proud of what we've accomplished in developing and delivering transformational medicines to patients," said Damien McDevitt, Chief Executive Officer of Akcea. "This acquisition by Ionis is a testament to the achievements of the Akcea team."

    "This transaction delivers immediate and certain value with a premium to Akcea shareholders," said Barbara Yanni, Chair of the Akcea Affiliate Transactions Committee. "Our close collaboration with Ionis has been key to enabling the launch of two commercial antisense medicines in just two years as well as advancing a late-stage pipeline and securing important partnerships."

    SIGNIFICANT FINANCIAL BENEFITS

    This transaction also further strengthens Ionis' financial position:

    • Ionis will realize more financial upside from Akcea's rich pipeline and commercial products.
    • Ionis will gain full access to Akcea's significant cash on hand of approximately $390 million as of June 30, 2020 and future cash flows to further invest in the Company's future and further support Ionis' capital allocation strategy.
    • Ionis will achieve meaningful cost synergies.

    TERMS OF THE AGREEMENT

    Under the terms of the agreement, Ionis will commence a tender offer for all outstanding shares of Akcea common stock not already owned by Ionis at a price of $18.15 per share in cash. The closing of the tender offer will be subject to a majority of Akcea's shares not already owned by Ionis, its affiliates or their respective directors and executive officers being tendered in the tender offer. 

    Promptly following the completion of the tender offer, Ionis will acquire all remaining shares of Akcea common stock at the same price of $18.15 per share in cash through a second-step merger. Ionis and Akcea expect to complete the transaction in the fourth quarter of 2020, subject to other customary closing conditions.

    Ionis expects to fund the acquisition through existing cash resources. The transaction is not subject to any financing condition.

    ADVISORS

    Goldman Sachs & Co. LLC and Stifel, Nicolaus & Company, Incorporated are serving as financial advisors to Ionis, and Skadden, Arps, Slate, Meagher & Flom LLP is serving as legal counsel to Ionis. Cowen is serving as financial advisor to the Affiliate Transactions Committee of Akcea's Board of Directors, and Ropes & Gray LLP is serving as legal counsel to the Affiliate Transactions Committee of Akcea's Board of Directors.

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of diseases, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

    ABOUT AKCEA THERAPEUTICS, INC.

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six medicines were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston, Massachusetts, and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow the Company on twitter at @akceatx.

    Notice to Investors and Security Holders               

    The tender offer referred to in this communication has not yet commenced. The description contained in this communication is neither an offer to purchase nor a solicitation of an offer to sell any securities, nor is it a substitute for the tender offer materials that Ionis will file with the Securities and Exchange Commission (the "SEC"). The solicitation and offer to buy shares of Akcea common stock will only be made pursuant to an offer to purchase and related tender offer materials. At the time the tender offer is commenced, Ionis will file a tender offer statement on Schedule TO and thereafter Akcea will file a solicitation/recommendation statement on Schedule 14D-9 with the SEC with respect to the Offer. THE TENDER OFFER MATERIALS (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND CERTAIN OTHER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT ON SCHEDULE 14D-9 WILL CONTAIN IMPORTANT INFORMATION. AKCEA SHAREHOLDERS ARE URGED TO READ THESE DOCUMENTS CAREFULLY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT HOLDERS SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SHARES. The offer to purchase, the related letter of transmittal and the solicitation/recommendation statement will be made available free of charge at the SEC's website at www.sec.gov. Additional copies may be obtained for free by contacting Ionis or Akcea, as applicable. Copies of the documents filed with the SEC by Ionis will be available free of charge on Ionis' internet website at https://ir.ionispharma.com/financial-information/sec-filings or by contacting Ionis' investor relations contact at (760) 603-2681. Copies of the documents filed with the SEC by Akcea will be available free of charge on Akcea's internet website at https://ir.akceatx.com/ or by contacting Akcea's investor relations contact at (617) 841-9535.

    In addition to the offer to purchase, the related letter of transmittal and certain other tender offer documents to be filed by Ionis, as well as the solicitation/recommendation statement to be filed by Akcea, Ionis and Akcea will also file quarterly and current reports with the SEC. Ionis' and Akcea's filings with the SEC are available to the public from commercial document-retrieval services and at the website maintained by the SEC at http://www.sec.gov.

    FORWARD-LOOKING STATEMENTS

    Ionis Pharmaceuticals, Inc. and Akcea Therapeutics, Inc. assume no obligation to update forward-looking statements contained in this communication as a result of new information or future events or developments except as required by law. This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc., the therapeutic and commercial potential of TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen) and the proposed acquisition of Akcea that are subject to risks and uncertainties that could cause actual results to differ materially from those expressly or implied by such statements. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of TEGSEDI and WAYLIVRA or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Risks and uncertainties also include, among other things, risks related to the satisfaction or waiver of the conditions to closing the proposed acquisition in the anticipated timeframe or at all, including uncertainties as to how many of Akcea's stockholders will tender their Shares in the tender offer and the possibility that the acquisition does not close; disruption from the transaction making it more difficult to maintain business and operational relationships; risks that anticipated synergies will not be realized or may be delayed; and the magnitude of transaction costs. Akcea's and Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's and Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Akcea's and Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from each company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company,"  "we," "our," and "us" refers to Ionis Pharmaceuticals or Akcea Therapeutics, as applicable.

    Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

     

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    SOURCE Ionis Pharmaceuticals, Inc.; Akcea Therapeutics, Inc.

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  30. BOSTON and CARLSBAD, Calif., Aug. 29, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), presented data from the Phase 2 clinical trial of vupanorsen (AKCEA-ANGPTL3-LRx) in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting for the European Society of Cardiology.

    Vupanorsen is an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases. In the Phase 2 study, vupanorsen met the primary endpoint of significant reductions in triglyceride (TG) levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability…

    BOSTON and CARLSBAD, Calif., Aug. 29, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), presented data from the Phase 2 clinical trial of vupanorsen (AKCEA-ANGPTL3-LRx) in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting for the European Society of Cardiology.

    Vupanorsen is an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases. In the Phase 2 study, vupanorsen met the primary endpoint of significant reductions in triglyceride (TG) levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability profile.

    "We are very encouraged by the demonstrated efficacy, safety and tolerability profile of vupanorsen," said Damien McDevitt, Ph.D., chief executive officer at Akcea. "There are millions of patients worldwide living with dyslipidemia that puts them at risk of cardiovascular events. By reducing ANGPTL3, vupanorsen has the potential to reduce the risk of cardiovascular events caused by dyslipidemia in many of these patients, thereby addressing a major area of continued unmet medical need. We look forward to working with Pfizer as they continue to advance this important clinical development program."

    Vupanorsen was developed using Ionis' proprietary LIgand Conjugated Antisense (LICA) technology platform to reduce the production of angiopoietin-like 3 (ANGPTL3) protein from the liver, a key regulator of triglyceride and cholesterol metabolism.

    The goal of the randomized, double-blind, placebo-controlled, dose-ranging Phase 2 study was to assess the safety and efficacy of vupanorsen. A total of 105 patients with hypertriglyceridemia (fasting plasma TG levels >150 mg/dL), type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) were randomized to three dosing cohorts in a 3:1 ratio (vupanorsen: placebo) within each cohort and treated for six months. The dosing cohorts explored different doses and dose regimens vs placebo, with patients receiving either 40 mg or 80 mg every four weeks or 20 mg every week. Participants received either vupanorsen or placebo via subcutaneous injection. Results from the Phase 2 study show:

    • Statistically significant dose-dependent reductions in fasting TGs at all dose levels, with the highest mean reduction of 53% at the dose of 80 mg every four weeks (44% mean reduction compared to placebo, P<0.0001)
    • Statistically significant dose-dependent reductions compared to placebo in ANGPTL3 (62%), very low-density lipoprotein (VLDL) cholesterol (38%), total cholesterol (19%), and non-high-density lipoprotein (non-HDL) cholesterol (18%) (numbers indicate mean reductions achieved with the 80 mg every four week dose)
    • No effect on glycemic parameters and no decrease in hepatic steatosis
    • No significant reductions in low-density lipoprotein cholesterol (LDL-C) levels compared to placebo in this patient population, which did not have high baseline LDL-C levels
    • A favorable tolerability and safety profile. The most common treatment-emergent adverse events were injection site reactions, which were mostly mild.

    "Antisense-mediated reduction of ANGPTL3 has the potential to address significant unmet needs in patients with cardiovascular diseases," said Daniel Gaudet, M.D., professor of medicine, Department of Medicine, University of Montreal. "Results from the Phase 2 study bring essential insights about this investigational therapy that may help guide disease management strategies and clinical research moving forward."

    "Clinical data from the Phase 2 study show an impressive and meaningful reduction in triglyceride levels and ANGPTL3, and add to the growing body of evidence supporting our LICA antisense technology  for large indications, such as cardiovascular disease," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "We believe vupanorsen has the potential to bring much-needed benefit to this patient population."

    In November 2019, Akcea and Ionis announced the closing of a worldwide exclusive licensing agreement with Pfizer Inc. for vupanorsen. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with this Phase 2 study. Pfizer plans to further evaluate vupanorsen in a Phase 2b study among statin-treated patients with elevated non-HDL-C and high triglyceride levels, in order to identify the optimal dose to maximize target engagement and lipid lowering. The Phase 2b study is expected to initiate in 2H 2020.

    ABOUT VUPANORSEN (AKCEA-ANGPTL3-LRx)

    AKCEA-ANGPTL3-LRx (vupanorsen) is an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases. This antisense medicine is designed to reduce the production of angiopoietin-like 3 (ANGPTL3) protein, a key regulator of triglyceride and cholesterol metabolism, in the liver. AKCEA-ANGPTL3-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery that people with a genetic deficiency in ANGPTL3 have reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides, and a decreased risk of diabetes and cardiovascular disease.1 In a previous Phase 1 study, subjects treated with AKCEA-ANGPTL3-LRx achieved robust, dose-dependent reductions in ANGPTL3, triglycerides, LDL-C, non-HDL-C and total cholesterol with a positive safety and tolerability profile.2 AKCEA-ANGPTL3-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.

    ABOUT AKCEA THERAPEUTICS

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    AKCEA AND IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the therapeutic and commercial potential of AKCEA-ANGPTL3-LRx. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of AKCEA-ANGPTL3-LRx or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea's and Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's and Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis.  In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Akcea's and Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from each company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company," "Companies," "we," "our," and "us" refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

    References

    1. JAMA Cardiol. 2018 Oct 1;3(10):957-966.
    2. N Engl J Med. 2017 Jul 20;377(3):222-232.
    ionis_Logo

     

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    SOURCE Akcea Therapeutics, Inc.; Ionis Pharmaceuticals, Inc.

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  31. BOSTON and CARLSBAD, Calif., Aug. 29, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), presented data today from the Phase 2 study of AKCEA-APOCIII-LRx in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting of the European Society of Cardiology.

    Results showed that AKCEA-APOCIII-LRx met primary and key secondary endpoints with significant reductions in triglyceride (TG) and apoC-III levels, and a favorable safety and tolerability profile in the treatment of patients with hypertriglyceridemia who have established cardiovascular disease (CVD) or are at risk for CVD. 

    "Hypertriglyceridemia and high levels of apoC-III are associated with increased residual risk for cardiovascular events, even in patients receiving appropriate lipid-lowering therapies. These results demonstrate that AKCEA-APOCIII-LRx can substantially reduce TG and apoC-III levels, and thus has the potential to fulfill an unmet need in this patient population," said Jean-Claude Tardif, M.D., director of the Research Center at the Montreal Heart Institute and professor of Medicine at University of Montreal.

    AKCEA-APOCIII-LRx is designed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform to inhibit production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Epidemiological studies show that apoC-III levels may help predict risk of CVD.

    "We are encouraged by the results from our Phase 2 study, in which treatment with AKCEA-APOCIII-LRx significantly reduced triglycerides and other atherogenic lipoproteins in patients with hypertriglyceridemia and a history of CVD, or a high risk for CVD," said William Andrews, M.D., FACP, chief medical officer at Akcea. "We look forward to further assessing AKCEA-APOCIII-LRx in other severe diseases associated with high triglyceride levels, including familial chylomicronemia syndrome (FCS), for which we plan to initiate a Phase 3 trial later this year."

    The Phase 2 study was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the safety, tolerability and efficacy of AKCEA-APOCIII-LRx in patients with hypertriglyceridemia and a clinical diagnosis of CVD or who are at high risk of CVD. The study was also designed to identify the optimal dose and dose regimen to lower TG, apoC-III and other lipid and lipoprotein levels for subsequent Phase 3 studies. The study involved 114 patients randomized to four cohorts and in a 4:1 ratio (treatment: placebo) within each cohort. AKCEA-APOCIII-LRx or placebo was administered via subcutaneous injection for at least six months, with some patients treated up to a year. Weekly, bi-weekly, and monthly dosing regimens were explored with total monthly doses ranging from 10 mg to 50 mg. Data from the Phase 2 study show:

    • Statistically significant dose-dependent reductions in fasting TGs compared to placebo at all dose levels with a 62% reduction at the highest dose (50 mg every four weeks), and with 91% of patients achieving TG levels of < 150 mg/dL (≤1.7 mmol/L) at this dose at six months
    • Significant reductions in apoC-III (up to 74%) and atherogenic lipoproteins including very low-density lipoprotein (VLDL) cholesterol (60%), non-high-density lipoprotein (non-HDL) cholesterol (24%), and apolipoprotein B, or apoB (16%)
    • High-density lipoprotein (HDL) cholesterol levels increased by up to 42%
    • AKCEA-APOCIII-LRx demonstrated a favorable tolerability and safety profile with mild treatment-emergent adverse events at the injection site being the most frequent

    "These data further demonstrate the tremendous value that our LICA antisense platform brings to patients suffering from a broad range of diseases," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "We look forward to advancing AKCEA-APOCIII-LRx into Phase 3 development to address patient populations with high triglyceride levels".   

    ABOUT AKCEA-APOCIII-LRx

    AKCEA-APOCIII-LRx is an investigational antisense medicine designed to reduce the production of apolipoprotein C-III, or apoC-III. ApoC-III is a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Genetically reduced levels of apoC-III are correlated to lower levels of triglycerides and lower risk of cardiovascular disease whereas elevated levels of apoC-III correlate with high triglyceride levels that have been associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome as well as elevated cardiovascular event risk. AKCEA-APOCIII-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. AKCEA-APOCIII-LRx will be entering Phase 3 development for patients with FCS, with plans to evaluate AKCEA-APOCIII-LRx in patients with other hypertriglyceridemia disorders. AKCEA-APOCIII-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.

    ABOUT AKCEA THERAPEUTICS

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    AKCEA AND IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the therapeutic and commercial potential of AKCEA-APOCIII-LRx. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of AKCEA-APOCIII-LRx or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea's and Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's and Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis.  In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Akcea's and Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from each company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company," "Companies," "we," "our," and "us" refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

     

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    SOURCE Akcea Therapeutics, Inc.; Ionis Pharmaceuticals, Inc.

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  32. CARLSBAD, Calif., Aug. 26, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) announced today that it will host a live webcast on Wednesday, September 2nd at 10:00 a.m. Eastern Time to review its cardio-renal franchise. The approximately 90-minute webcast will include presentations from Brett P. Monia, Ph.D., chief executive officer; Sam Tsimikas, M.D., senior vice president, global cardiovascular development; Sanjay Bhanot, M.D., Ph.D., chief medical officer; and Richard Geary, Ph.D., executive vice president, development. The agenda for the webcast will be as follows:

    Welcome and Introductions

    Wade Walke

    Ionis – The Leader in RNA-targeted Drug Discovery and Development

    Brett Monia

    Ionis – Leading the Way in Targeting Cardiovascular and Renal Diseases

    Sam Tsimikas

    Medicines Targeting Triglyceride-driven Diseases

    ο    Akcea-APOCIII-LRx

    ο   Vupanorsen (AKCEA-ANGPTL3-LRx)

    Sam Tsimikas

    Thrombosis: IONIS-FXI-LRx

    Sanjay Bhanot

    Apolipoprotein(a): AKCEA-APO(a)-LRx

    Sam Tsimikas

    Transthyretin Amyloid Cardiomyopathy: AKCEA-TTR-LRx

    Richard Geary

    Treatment Resistant Hypertension: IONIS-AGT-LRx

    Richard Geary

    Conclusions

    Brett Monia

    Q&A

    All

    Interested parties may access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time at the same address.

    About Ionis Pharmaceuticals

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

    To learn more about Ionis visit www.ionispharma.com and follow us on twitter @ionispharma.

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    SOURCE Ionis Pharmaceuticals, Inc.

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  33. BOSTON and CARLSBAD, Calif., Aug. 24, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), today announced that data from the Phase 2 clinical trial of vupanorsen (AKCEA-ANGPTL3-LRx), an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases, will be presented in a Late Breaking Clinical Trial Session at the upcoming ESC Congress 2020, the annual meeting of the European Society of Cardiology, which is expected to be the world's largest online gathering of cardiovascular professionals and is taking place August 29-September 1, 2020.

    BOSTON and CARLSBAD, Calif., Aug. 24, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), today announced that data from the Phase 2 clinical trial of vupanorsen (AKCEA-ANGPTL3-LRx), an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases, will be presented in a Late Breaking Clinical Trial Session at the upcoming ESC Congress 2020, the annual meeting of the European Society of Cardiology, which is expected to be the world's largest online gathering of cardiovascular professionals and is taking place August 29-September 1, 2020.

    Vupanorsen was developed using Ionis' proprietary LIgand Conjugated Antisense (LICA) technology platform to reduce the production of angiopoietin-like 3 (ANGPTL3) protein, a key regulator of triglyceride and cholesterol metabolism, in the liver. The Phase 2 dose-ranging clinical trial evaluated the safety and efficacy of vupanorsen in patients with hypertriglyceridemia, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). 

    In November 2019, Akcea and Ionis announced the closing of the worldwide exclusive licensing agreement with Pfizer Inc. for vupanorsen (AKCEA-ANGPTL3-LRx). Under terms of the agreement, Akcea and Ionis received a $250 million upfront license fee, which was split equally between the two companies. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with this Phase 2 study.

    Following are details about the late-breaking virtual presentation at ESC Congress 2020, which will be made available on the Akcea website:

    • Late-Breaking Science in Lipids: ANGPTL3 Antisense Oligonucleotide to Lower Triglycerides by Daniel Gaudet, M.D., professor of medicine, Department of Medicine, University of Montreal

      Oral Presentation: Saturday, August 29, 2020, 3:00 a.m. ET/9:00 a.m. CEST

    ABOUT VUPANORSEN (AKCEA-ANGPTL3-LRx)

    AKCEA-ANGPTL3-LRx (vupanorsen) is an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases. This antisense medicine is designed to reduce the production of angiopoietin-like 3 (ANGPTL3) protein, a key regulator of triglyceride and cholesterol metabolism, in the liver. AKCEA-ANGPTL3-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery that people with a genetic deficiency in ANGPTL3 have reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides, and a decreased risk of cardiovascular disease.1 In a previous Phase 1 study, patients treated with AKCEA-ANGPTL3-LRx achieved robust, dose-dependent reductions in ANGPTL3, triglycerides, LDL-C, non-HDL-C and total cholesterol with a positive safety and tolerability profile.2 AKCEA-ANGPTL3-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.

    ABOUT AKCEA THERAPEUTICS

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    AKCEA AND IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the therapeutic and commercial potential of AKCEA-ANGPTL3-LRx. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of AKCEA-ANGPTL3-LRx or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea's and Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's and Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Akcea's and Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from each company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company," "Companies," "we," "our," and "us" refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

    References

    1.    JAMA Cardiol. 2018 Oct 1;3(10):957-966.

    2.    N Engl J Med. 2017 Jul 20;377(3):222-232.

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    SOURCE Akcea Therapeutics, Inc.; Ionis Pharmaceuticals, Inc.

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  34. BOSTON and CARLSBAD, Calif., Aug. 18, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), today announced that data from the Phase 2 study of AKCEA-APOCIII-LRx will be presented in a Late Breaking Clinical Trial Session at the upcoming ESC Congress 2020, the annual meeting of the European Society of Cardiology, which is expected to be the world's largest online gathering of cardiovascular professionals, taking place August 29-September 1, 2020.

    AKCEA-APOCIII-LRx is an antisense drug developed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform and is designed to reduce the production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of serum triglycerides. AKCEA-APOCIII-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis. A prior Phase 1/2 study of AKCEA-APOCIII-LRx in healthy volunteers with elevated triglyceride levels showed dose-dependent reductions in apoC-III, triglycerides and atherogenic lipoproteins, and increase in high-density lipoprotein cholesterol (HDL-C) following treatment.

    Following are details about the Phase 2 study late-breaking virtual presentation at the ESC Congress, which will be made available on the Akcea website:

    • Late-Breaking Science in Lipids: Apolipoprotein C-III Reduction in Cardiovascular Disease by Professor Jean-Claude Tardif, Montreal Heart Institute, University of Montreal

      Oral Presentation: Saturday, August 29, 2020, 2:50 a.m. ET/8:50 a.m. CEST

    ABOUT AKCEA-APOCIII-LRx

    AKCEA-APOCIII-LRx is a ligand conjugated antisense (LICA) drug designed to reduce the production of apolipoprotein C-III, or apoC-III. ApoC-III is a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Genetically reduced levels of apoC-III are correlated to lower levels of triglycerides and lower risk of cardiovascular disease whereas elevated levels of apoC-III correlate with high triglyceride levels that have been associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome as well as elevated cardiovascular event risk. AKCEA-APOCIII-LRx is in Phase 2 development for hypertriglyceridemia and established cardiovascular disease. Akcea and Ionis intend to pursue development in familial chylomicronemia syndrome, or FCS, and are considering pursuing development in additional indications.  

    ABOUT AKCEA THERAPEUTICS

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

    ABOUT IONIS PHARMACEUTICALS, INC.

    As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

    AKCEA AND IONIS FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the therapeutic and commercial potential of AKCEA-APOCIII-LRx. Any statement describing Akcea's or Ionis' goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of AKCEA-APOCIII-LRx or other of Akcea's or Ionis' drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea's and Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's and Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's and Ionis' programs are described in additional detail in Akcea's and Ionis' quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from each company.

    In this press release, unless the context requires otherwise, "Ionis," "Akcea," "Company," "Companies," "we," "our," and "us" refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

     

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    SOURCE Akcea Therapeutics, Inc.; Ionis Pharmaceuticals, Inc.

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  35. BOSTON, Aug. 13, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., today announced that the German Association of Statutory Sick Funds has agreed upon new pricing and reimbursement of WAYLIVRA® (volanesorsen) as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. WAYLIVRA has been commercially available in Germany since August 15, 2019. As part of reimbursement and market access protocol in Germany, Akcea was required to renegotiate the WAYLIVRA launch price 12 months after first commercialization, which will…

    BOSTON, Aug. 13, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., today announced that the German Association of Statutory Sick Funds has agreed upon new pricing and reimbursement of WAYLIVRA® (volanesorsen) as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. WAYLIVRA has been commercially available in Germany since August 15, 2019. As part of reimbursement and market access protocol in Germany, Akcea was required to renegotiate the WAYLIVRA launch price 12 months after first commercialization, which will go into effect on August 15, 2020.

    "We are pleased that renegotiations in Germany were swiftly completed, demonstrating that payers in the region continue to recognize the value that WAYLIVRA offers to FCS patients. While WAYLIVRA has been commercially available to FCS patients in the region for some time, achieving this new, 2-year mutually agreed upon pricing and reimbursement is a significant milestone for the global FCS community of patients and caregivers, who are currently underserved," said Michael Pollock, SVP, head of Europe at Akcea. "We continue to build on our momentum in Europe and are on track to launch WAYLIVRA in additional European countries with the goal of bringing this much needed therapy to all eligible patients living with FCS."

    "FCS patients in Germany as well as their families have been living with the significant burden of this disease for years, including physical, social, emotional and financial effects, and I am pleased to be able to offer appropriate patients a treatment option supported by extensive clinical data including results from the Phase 3 APPROACH study," said Professor Ioanna Gouni-Berthold from University of Cologne.

    FCS is a debilitating genetic disease caused by impaired function of the enzyme lipoprotein lipase (LPL), which results in elevated triglyceride levels and significant risk and disease burden, including unpredictable and potentially fatal acute pancreatitis as well as chronic complications due to permanent organ damage. It is estimated that there are between 3,000 to 5,000 people living with FCS worldwide. WAYLIVRA is designed to reduce the production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of plasma triglycerides.

    About WAYLIVRA® (volanesorsen)

    With conditional marketing authorization from the European Commission (EC) as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate, WAYLIVRA is now the only therapy indicated for people with familial chylomicronemia syndrome (FCS). Akcea is working to confirm a path forward for WAYLIVRA in the U.S. and Canada.

    WAYLIVRA, a product of Ionis' proprietary antisense technology, is designed to reduce the production of apoC-III, a protein that regulates plasma triglycerides and may also affect other metabolic parameters.

    The European Commission's marketing authorization of WAYLIVRA is based on results from the Phase 3 APPROACH study and the ongoing APPROACH Open Label Extension (OLE) study and is supported by results from the Phase 3 COMPASS study. Results from the Phase 3 APPROACH trial, the largest study ever conducted in patients with FCS, show that in comparison to placebo, treatment with WAYLIVRA reduced triglycerides 77% (-94% when compared to placebo). All patients in the trial maintained a low-fat diet.

    WAYLIVRA is associated with risk of thrombocytopenia. Enhanced monitoring is required to support early detection and management of thrombocytopenia. The most frequently observed adverse reactions (more than 10%) during treatment with WAYLIVRA were events associated with injection site reactions, immunogenicity and reduction in platelet levels. 

    The WAYLIVRA Early Access Program (EAP) has been initiated in Europe, the U.S. and Canada and is currently enrolling eligible patients. Click here for more information on the WAYLIVRA EAP. For more information on WAYLIVRA, please visit www.WAYLIVRA.eu.

    About FCS

    FCS is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia (>880mg/dL or 10mmol/L) and a risk of unpredictable and potentially fatal acute pancreatitis. Because of limited LPL production or function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90% triglycerides. In addition to pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic (type 3c) diabetes. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognition that affect their ability to work. People with FCS also report major emotional and psychosocial effects including anxiety, social withdrawal, depression and brain fog. Additional information on FCS is available at www.fcsfocus.com, through the LPLD Alliance at www.lpldalliance.org and through The FCS Foundation at http://www.livingwithfcs.org. For a full list of organizations supporting the FCS community worldwide, please click here

    ABOUT AKCEA THERAPEUTICS, INC.

    Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six medicines were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston, Massachusetts, and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

    FORWARD-LOOKING STATEMENT

    This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. Any statement describing Akcea's goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of TEGSEDI®, WAYLIVRA® and Akcea's other medicines in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Akcea's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's programs are described in additional detail in Akcea's quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from the company.

    In this press release, unless the context requires otherwise, "Ionis", "Akcea," "Company," "Companies" "we," "our," and "us" refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

    Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.

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    SOURCE Akcea Therapeutics, Inc.

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  36. CARLSBAD, Calif., Aug. 5, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) today reported its financial results for the second quarter of 2020 and recent business highlights.

    "The first half of this year was marked by numerous important achievements. Our Phase 3 programs progressed, we advanced our cardio-renal, metabolic and neurological disease franchises and added new medicines to our Ionis-owned pipeline. Together, these catalysts moved us closer to delivering 10 or more marketing applications through 2025, which we expect to result in a number of new commercial medicines. In the second half of this year, we are expanding the reach of our technology in neurological and pulmonary diseases, as studies in sporadic ALS and COPD get underway. We also look forward to proof-of-concept data from additional mid-stage programs," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "Our achievements, together with our significant financial resources, position us to realize my vision for Ionis – to lead in the delivery of transformational medicines for patients around the world."

    Second Quarter 2020 Financial Results and Highlights

    • On track to achieve financial guidance of being meaningfully profitable this year
      • Net income of $8 million on a non-GAAP basis and a net loss of $32 million on a GAAP basis
    • Achieved quarter over quarter growth in commercial and R&D revenues
      • Commercial revenue from SPINRAZA® (nusinersen) royalties increased to $72 million
      • Product sales from TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen) increased to $16 million
      • R&D revenue increased to more than $55 million, including $26 million from Ionis' neurological disease franchise, $13 million from the oncology franchise and more than $10 million from the cardio-renal franchise
    • Cash position of more than $2.3 billion provides substantial financial resources to continue executing on strategic goals

    "We ended the second quarter with net income on a non-GAAP basis, an increase compared to our first quarter results. Looking ahead, we are maintaining our 2020 financial guidance and expect revenue and earnings growth in the second half of this year. With our substantial resources, we are well positioned to continue executing on our ambitious agenda and to deliver increasing value near-term and into the future," said Elizabeth L. Hougen, chief financial officer of Ionis.

    All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of non-GAAP and GAAP measures, which is provided later in this release.

    Commercial Medicine Highlights

    • SPINRAZA: a global foundation-of-care for the treatment of spinal muscular atrophy (SMA) patients of all ages
      • $495 million in worldwide sales in the second quarter of this year
      • More than 11,000 patients were on SPINRAZA treatment worldwide at the end of the second quarter, including patients across commercial, expanded access and clinical trial settings
      • The Phase 4 RESPOND study to evaluate SPINRAZA benefit in patients with a suboptimal clinical response to Zolgensma® (onasemnogene abeparvovec) is expected to begin early next year
      • The DEVOTE study evaluating a higher dose of SPINRAZA with the potential to deliver even greater efficacy in SMA patients of all ages is progressing
      • New clinical data from the NURTURE and SHINE studies, as well as new real-world data, further support SPINRAZA's durable efficacy and established safety profile across SMA patients of all ages
    • TEGSEDI: the only approved at-home subcutaneous therapy for the treatment of hereditary transthyretin amyloidosis (hATTR) with polyneuropathy in adult patients
      • Commercially available in 15 countries
      • Reimbursement approved in Portugal, Spain, Italy and Austria
      • Expanding commercial availability in additional EU countries and in Latin America this year
    • WAYLIVRA: the only approved treatment in the EU for adults with genetically confirmed familial chylomicronemia syndrome (FCS) at high risk for pancreatitis
      • Launch progressing in Germany, Austria, Greece and through the ATU in France; launching in additional EU countries this year
      • Filed for marketing approval in Brazil; refiling new drug application for U.S. marketing authorization

    Second Quarter 2020 and Recent Pipeline Highlights

    • Completed enrollment in the global GENERATION HD1 Phase 3 study of tominersen in patients with Huntington's disease
    • Progressed multiple neurological disease medicines under Ionis' broad Biogen collaboration
      • Published data from the Phase 1/2 study of tofersen in the New England Journal of Medicine
      • Progressed the IONIS-MAPTRx long-term extension study in patients with Alzheimer's disease and achieved a $12 million milestone payment
      • Advanced ION464 into a Phase 1/2 study in patients with multiple system atrophy and achieved an $18 million milestone payment
    • Advanced medicines for the treatment of cancer and immune-mediated GI disease
      • Licensed ION736 to AstraZeneca for the treatment of cancer and achieved a $13 million license fee
      • Initiated a Phase 1 study of ION253 for the treatment of immune-mediated GI disease and achieved a $5 million milestone payment from Janssen
    • Expanded the Ionis-owned pipeline with the addition of ION363 for the treatment of FUS-ALS

    Upcoming Catalysts 

    • Report clinical proof-of-concept results for four or more programs
    • Present positive Phase 2 results from vupanorsen and AKCEA-APOCIII-LRx
    • Initiate a Phase 3 study of AKCEA-APOCIII-LRx in patients with FCS
    • Initiate a registration study of ION363 in patients with FUS-ALS
    • Initiate a Phase 1/2 study of ION541 in patients with sporadic ALS
    • Initiate a Phase 2 study of IONIS-ENaC-2.5Rx in patients with chronic obstructive pulmonary disease (COPD)
    • Initiate a Phase 2 study of IONIS-FXI-LRx in patients with clotting disorders
    • Initiate a Phase 2 study of IONIS-HBVRx in patients with hepatitis B virus infection
    • Advance additional new medicines into development

    Revenue

    Ionis' revenue was comprised of the following (amounts in millions):





    Three months ended,



    Six months ended





    June 30,



    June 30,





    2020



    2019



    2020



    2019

    Revenue:













         Commercial revenue:

















    SPINRAZA royalties



    $72



    $71



    $138



    $130

    Product sales, net



    16



    10



    32



    17

    Licensing and royalty revenue



    2



    7



    4



    9

    Total commercial revenue



    90



    88



    174



    156

    R&D Revenue:

















    Amortization from upfront payments



    28



    41



    49



    75

    Milestone payments



    7



    12



    30



    52

    License fees



    15



    22



    15



    173

    Other services