RARE Ultragenyx Pharmaceutical Inc.

133.09
-2.06  -2%
Previous Close 135.15
Open 136.62
52 Week Low 31.99
52 Week High 177.965
Market Cap $8,804,675,156
Shares 66,155,798
Float 49,636,966
Enterprise Value $8,219,889,099
Volume 501,155
Av. Daily Volume 518,165
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Upcoming Catalysts

Drug Stage Catalyst Date
GTX-102
Angelman Syndrome
Phase 1/2
Phase 1/2
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Drug Pipeline

Drug Stage Notes
UX053
GSDIII debrancher deficiency
Phase 1/2
Phase 1/2
Phase 1/2 trial to commence 2H 2021.
UX701
Wilson Disease
Phase 1/2
Phase 1/2
Phase 1/2/3 trial to commence 1H 2021.
DTX401
Glycogen Storage Disease Type Ia (GSDIa)
Phase 1/2
Phase 1/2
Phase 1/2 trial ongoing. Phase 3 trial to commence 1H 2021.
DTX301
Ornithine Transcarbamylase (OTC) Deficiency
Phase 1/2
Phase 1/2
Phase 1/2 ongoing. Phase 3 trial to commence 2H 2021.
UX007 (triheptanoin)
Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
Approved
Approved
FDA Approval announced June 30, 2020.
Burosumab
Tumor-induced osteomalacia (TIO)
Approved
Approved
FDA Approval announced June 18, 2020.
UX007 (triheptanoin)
Glut1 DS patients with the movement disorder phenotype
Phase 3
Phase 3
Phase 3 data released October 26, 2018 - endpoints not met.
Crysvita (Burosumab)
X-Linked Hypophosphatemia (XLH)
Approved
Approved
Approval announced April 17, 2018.
MEPSEVII (vestronidase alfa)
Mucopolysaccharidosis 7 (MPS 7)
Approved
Approved
Approved under priority review November 15, 2017.
Aceneuramic acid extended release (Ace-ER)
GNE Myopathy
Phase 3
Phase 3
Phase 3 data released August 22, 2017 - endpoints not met.

Latest News

  1. Clinical trial will utilize a single-protocol Phase 1/2/3 design

    UX701 manufacturing complete at commercial quality and scale using HeLa PCL technology

    First patient to be dosed in the first half of 2021

    NOVATO, Calif., Jan. 21, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for UX701, an investigational AAV9 gene therapy being evaluated for the treatment of Wilson Disease. Enrollment in a seamless single-protocol Phase 1/2/3 study is expected to begin…

    Clinical trial will utilize a single-protocol Phase 1/2/3 design

    UX701 manufacturing complete at commercial quality and scale using HeLa PCL technology

    First patient to be dosed in the first half of 2021

    NOVATO, Calif., Jan. 21, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for UX701, an investigational AAV9 gene therapy being evaluated for the treatment of Wilson Disease. Enrollment in a seamless single-protocol Phase 1/2/3 study is expected to begin in the first half of 2021. This will be the company's third in-house clinical gene therapy program and the second program in the clinic with the HeLa producer cell line manufacturing system.

    "FDA IND clearance allows for the advancement of this new gene therapy into the clinic and brings forward the hope for a new treatment for patients with Wilson Disease. UX701 has the potential to directly address the underlying basis of disease by restoring the normal transport and excretion of copper," said Eric Crombez, M.D., Chief Medical Officer of the Ultragenyx Gene Therapy development unit. "The seamless Phase 1/2/3 clinical trial design will allow us to efficiently evaluate safety and efficacy of UX701 before studying an optimal dose in a larger number of patients to support registration. We appreciate the agency's support for a novel clinical trial design that could bring this important potentially new treatment to the greatest number of patients as efficiently as possible."

    Study Design

    UX701 will be studied in a seamless, single-protocol Phase 1/2/3 clinical trial. Manufacture and testing of GMP-grade drug product to supply the clinical study are complete using the company's proprietary HeLa 2.0 producer cell line (PCL) process at the 2,000 liter scale.

    Stage 1 (evaluation of initial safety and dose finding)

    In the first stage of the study, the safety and efficacy of three dose levels of UX701 will be evaluated in 27 patients (nine per cohort), randomized 2-to-1 (gene therapy versus placebo). The dose cohorts will be enrolled sequentially using ascending doses. The patients will be followed for 52 weeks before transitioning to long-term follow-up and selecting a pivotal dose. The dose will be determined based on the safety profile, changes in biomarkers of copper metabolism (e.g. 24-hr urinary copper, ceruloplasmin concentration, ceruloplasmin activity, non-ceruloplasmin bound copper, and total serum copper), and the reduction in the use of the current standard (SOC), copper chelator and/or zinc.

    Stage 2 (optimal dose evaluation for pivotal clinical data generation)

    The second and pivotal stage will use the dose selected from Stage 1 and enroll an additional 63 patients, randomized 2-to-1 (gene therapy versus placebo). The co-primary endpoints in Stage 2 will evaluate the effect of UX701 on copper regulation based on 24-hour urinary copper concentration and percent reduction in SOC at Week 52. Key secondary endpoints in Stage 2 include the effect of UX701 on additional biomarkers of copper metabolism and patient- and clinician-reported outcomes from a modified Wilson Disease Functional Rating Scale.

    Stage 3 (long-term follow-up)

    All patients in Stage 1 and Stage 2 who are randomized to receive placebo may be eligible to receive UX701 at the Stage 2 dose. Patients receiving UX701 will be continued to be monitored for long term safety and durability of response.

    About Wilson Disease

    Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be managed by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and debilitating side effects. Wilson disease affects more than 50,000 individuals in the developed world.

    About UX701

    UX701 is an investigational AAV type 9 gene therapy designed to deliver stable expression of a truncated version of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to improve copper distribution and excretion from the body and reverse pathological findings of Wilson liver disease. UX701 was granted Orphan Drug Designation in the United States and European Union.

    About Ultragenyx

    Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

    The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx's strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

    For more information on Ultragenyx, please visit the company's website at www.ultragenyx.com.

    Forward-Looking Statements

    Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the effects from the COVID-19 pandemic on the company's clinical activities, business and operating results, risks related to reliance on third party partners to conduct certain activities on the company's behalf, uncertainty and potential delays related to clinical drug development, smaller than anticipated market opportunities for the company's products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company's future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx's products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on October 27, 2020, and its subsequent periodic reports filed with the Securities and Exchange Commission.

    Contact Ultragenyx Pharmaceutical Inc.

    Investors & Media

    Joshua Higa

    415-660-0951



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  2. The February 6, 2020 Emerald Groundhog Day Investment Forum began with a special presentation from Emerald's CEO and Life Sciences research directors discussing the new COVID-19 virus that was beginning to emerge in the western world. One year later, the pervasive pandemic will make the February 4, 2021 Forum a virtual online-only event. Emerald Asset Management invites you to join us for the 28th annual Emerald Groundhog Day Investment Forum, the unofficial kick-off to the year ahead as Emerald's team of analysts and portfolio managers will present their key investment themes and trends for 2021, focusing on these key sectors:

    • Banking & Finance
    • Consumer
    • Energy
    • Industrials
    • Life Sciences
    • Technology

    Emerald's team will be joined…

    The February 6, 2020 Emerald Groundhog Day Investment Forum began with a special presentation from Emerald's CEO and Life Sciences research directors discussing the new COVID-19 virus that was beginning to emerge in the western world. One year later, the pervasive pandemic will make the February 4, 2021 Forum a virtual online-only event. Emerald Asset Management invites you to join us for the 28th annual Emerald Groundhog Day Investment Forum, the unofficial kick-off to the year ahead as Emerald's team of analysts and portfolio managers will present their key investment themes and trends for 2021, focusing on these key sectors:

    • Banking & Finance
    • Consumer
    • Energy
    • Industrials
    • Life Sciences
    • Technology

    Emerald's team will be joined by noted economist Joel Naroff and senior executives from companies that exemplify the trends identified by Emerald and who will provide insights on the state of their industries and sectors.

    "Our Life Sciences team gave our audience early insights into the spreading COVID-19 virus," said Emerald CEO and Founder Joseph E. Besecker. "It's this type of information and analysis that is so critical to investors as we begin 2021 with the pandemic still raging and political turmoil leading into the inauguration of President Biden," he said.

    The Groundhog Day Investment Forum will be held online beginning at 11:00am EST on Thursday, February 4th. Attendees can register and receive additional information at https://www.teamemerald.com/event/groundhog-day-investment-forum.

    "We say that the investment year begins in earnest with our annual Forum," said Emerald Director of Research Joseph W. Garner. "The convergence of investment professionals, joined by senior corporate leaders, will give our online audience a real-time perspective and insight into the path forward for 2021," he said.

    The first Emerald Groundhog Day Investment Forum was held in 1994 and has grown to become a definitive kick-off conference for investors focusing on small- and mid-cap companies. This year senior executives from several public and private companies and Emerald are scheduled to present.

    The presenting companies confirmed to date include: American Superconductor Corp. (NASDAQ:AMSC); Cogent Communications Holdings Inc. (NASDAQ:CCOI); Echo Global Logistics Inc. (NASDAQ:ECHO); Everi Holdings Inc. (NYSE:EVRI); Freshpet Inc. (NASDAQ:FRPT); MACOM Technology Solutions Holdings Inc. (NASDAQ:MTSI); New Fortress Energy Inc. (NASDAQ:NFE); Silvergate Capital Corp. (NYSE:SI); The Simply Good Foods Company (NASDAQ:SMPL); Trex Company, Inc. (NYSE:TREX); Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE). Additional companies may be added in the coming days.

    A full list of presenting companies, seminars by Emerald's investment professionals and registration details are available on Emerald's website at https://www.teamemerald.com/event/groundhog-day-investment-forum.

    Emerald Asset Management PA, LLC is a diversified investment management holding company that operates through its subsidiaries Emerald Advisers LLC, Emerald Mutual Fund Advisers Trust, Emerald Separate Account Management LLC, Emerald Direct Lending Advisers LLC and EmStone Advisers LLC. Managing client funds since 1992, assets managed by these companies totaled approximately $6.1 billion as of December 31, 2020. "Driven by Research," Emerald employs an intense fundamental, research-focused investment philosophy and focuses primarily on growth and value oriented equity investing and income oriented investing. Emerald and its subsidiaries maintain offices in King of Prussia and Pittsburgh, Pennsylvania and Cleveland, Ohio. Its global headquarters is located in Leola, PA.

    Emerald Asset Management PA, LLC

    3175 Oregon Pike

    Leola, PA 17540

    717.556.8900

    800.722.4123

    www.TeamEmerald.com

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  3. Preliminary 2020 Crysvita revenue in Ultragenyx Territories of $137 million to $139 million

    2021 Crysvita Ultragenyx revenue expected in the range of $180 million to $190 million

    Year-end 2020 cash balance of approximately $1.2 billion

    NOVATO, Calif., Jan. 11, 2021 (GLOBE NEWSWIRE) --  Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, today reported preliminary unaudited 2020 Crysvita revenue in Ultragenyx territories and cash and investments at year end 2020 and provided 2021 revenue guidance for Crysvita in Ultragenyx territories.

    "The strong performance of Crysvita and our other two commercial…

    Preliminary 2020 Crysvita revenue in Ultragenyx Territories of $137 million to $139 million

    2021 Crysvita Ultragenyx revenue expected in the range of $180 million to $190 million

    Year-end 2020 cash balance of approximately $1.2 billion

    NOVATO, Calif., Jan. 11, 2021 (GLOBE NEWSWIRE) --  Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, today reported preliminary unaudited 2020 Crysvita revenue in Ultragenyx territories and cash and investments at year end 2020 and provided 2021 revenue guidance for Crysvita in Ultragenyx territories.

    "The strong performance of Crysvita and our other two commercial therapies across four indications have propelled our growth as a commercial rare disease company," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "This success has enabled us to rapidly advance our diversified pipeline with six programs in the clinic across multiple modalities, including multiple larger rare disease opportunities that could be first time treatments or major advances for patients and significant drivers of growth."

    Financial Update

    2020 Preliminary Crysvita1 Revenue (unaudited)

    Crysvita revenue in Ultragenyx territories for the year ended December 31, 2020 is approximately $137 million to $139 million. This is at the top end of the guidance range of $130 million to $140 million that was provided during the third quarter financial results and at the beginning of 2020, despite COVID-19 impact.

    2021 Crysvita1 Guidance

    For 2021, Crysvita revenue in the Ultragenyx territories is estimated to be between $180 million and $190 million.

    2020 Ending Cash Position (unaudited)

    Cash, cash equivalents, and available-for-sale investments were approximately $1.2 billion as of December 31, 2020, which includes net proceeds of approximately $435 million received from the underwritten public offering of its common stock and net proceeds of approximately $80 million from the sale of a portion of the company's investment in Arcturus Therapeutics.

    The 2020 revenue and cash position included in this release are preliminary and prior to the completion of review and audit procedures by Ultragenyx's external auditors, and are therefore subject to adjustment. The preliminary revenue results are based on management's initial analysis of operations for the quarter and year ended December 31, 2020. The Company expects to issue full financial results for the fourth quarter and fiscal year 2020 in February 2021.

    Recent Updates and 2021 Milestones

    DTX401 for Glycogen Storage Disease Type Ia (GSDIa): Positive longer-term data from Phase 1/2 study; Phase 3 study expected to initiate in the first half of 2021

    • In the Phase 1/2 study, all nine patients in the first three cohorts continue to respond to treatment and demonstrate continued glucose control while significantly tapering cornstarch glucose replacement therapy. All three patients in a fourth and final cohort, which utilizes prophylactic steroids, have been dosed at the same dose as Cohorts 2 and 3, are doing well and have demonstrated early reduction in daily cornstarch intake.
    • The company has held Scientific Advice and End of Phase 2 meetings with the European Medicines (EMA) and U.S. Food and Drug Administration (FDA), respectively. This feedback is being incorporated into the Phase 3 design, and finalization is pending.
    • The Phase 3 study is expected to initiate in the first half of 2021. The planned 48-week study will enroll approximately 50 patients, randomized 1:1 to DTX401 or placebo. Ultragenyx intends to study glycemic control by assessing the reduction in cornstarch requirements while maintaining or improving glucose control.

    DTX301 for Ornithine Transcarbamylase (OTC) Deficiency: Strong, durable responses in Phase 1/2 study; Phase 3 study expected to start in second half 2021

    • In the Phase 1/2 study, all six responders in the first three cohorts demonstrated durable metabolic control, including greater than two-year sustained responses in the earliest treated patients. Two of three patients in a fourth and final cohort, which utilizes prophylactic steroids, have been dosed at the same dose as Cohort 3. Both patients are doing well clinically with good metabolic control and without any safety issues. The third patient in the cohort, who has not yet been dosed due to delays related to COVID-19, is expected to be dosed this month.
    • Ultragenyx has received Scientific Advice from the EMA and has an End of Phase 2 meeting scheduled with the FDA late in the first quarter of 2021. These discussions and prior discussions are being incorporated into the Phase 3 plans.
    • A Phase 3 study is expected to begin in the second half of 2021. The proposed 48-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The change in 24 hour ammonia levels is the expected primary endpoint, supported by change in the rate of ureagenesis as a key secondary endpoint.

    GTX-102 for Angelman Syndrome: Phase 1/2 data demonstrate substantial clinical activity; Study expected to resume first half 2021 with additional data anticipated in second half 2021

    • All five patients in the Phase 1/2 study demonstrated improvements in at least 3 disease domains and scores of ‘much improved' or ‘very much improved' in 2 disease domains (mean global change +2.4 out of +3). Disease domains include communication, behavior, sleep, gross motor function, and fine motor function as measured by the Clinical Global Impression of Improvement Scale for Angelman Syndrome (CGI-I-AS). All five patients had a grade 1 or 2 serious adverse event (SAE) of lower extremity weakness associated with local inflammation in the region of intrathecal administration in the lower back at the higher doses of GTX-102. Dosing was paused after the first SAE onset was observed and the study is on clinical hold. The SAE has fully resolved in all five patients, and clinical improvements have been sustained beyond resolution of the SAE. There have been no other safety events following discontinuation of treatment reported to date.
    • Ultragenyx has submitted a substantial information amendment to the IND including follow-up safety information for the five patients dosed and toxicology data in nonhuman primates that demonstrate no evidence of this safety issue at higher repeat dosing. A safety evaluation of the SAEs included in the amendment supports causality due to local contact toxicity. An amended dosing and administration plan has been proposed to the FDA. These changes are expected to reduce the local contact time and concentration, and the new dosing plan is within the observed range of clinical activity but below doses associated with SAEs. The study is expected to resume enrollment and dosing in the first half of 2021, following resolution of FDA requests and approval to proceed.
    • A Clinical Trial Application (CTA) has already been submitted in Canada and a protocol and information amendment similar to what has been proposed to FDA will be submitted. The company is in the process of expanding the study to other countries using the amended dosing and administration plan.
    • Additional interim data from the study are expected in the second half 2021.

    UX701 for Wilson Disease: Phase 1/2/3 IND submitted; study start expected first half 2021

    • Ultragenyx has submitted an Investigational New Drug (IND) application for UX701, an AAV9 gene therapy for the treatment of Wilson Disease. UX701 has received orphan drug designation by the FDA and the EMA. The company expects to initiate a seamless single-protocol Phase 1/2/3 study in the first half of 2021.

    UX053 for Glycogen Storage Disease Type III (GSDIII) Debrancher Deficiency: IND first half 2021 and study initiation second half 2021

    • Ultragenyx plans to submit an IND application for UX053, an mRNA/lipid nanoparticle (LNP) for the treatment of GSDIII debrancher deficiency, in the first half of 2021 and to begin the Phase 1/2 study in the second half of 2021.

    Setrusumab (UX143) for Osteogenesis Imperfecta (OI): Pediatric Phase 2/3 study expected to begin in second half 2021

    • Ultragenyx is currently planning a pediatric Phase 2/3 study of setrusumab, a monoclonal antibody for the treatment of OI, a large genetic bone disorder. A separate pivotal study is also being planned for adults with OI.
    • Ultragenyx announced that it entered into a collaboration and license agreement with Mereo BioPharma for setrusumab in December 2020. The completion of the transaction is subject to Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR) review and the satisfaction of other customary closing conditions. Mereo has previously completed a Phase 2b study of setrusumab in adults with OI that demonstrated a dose-dependent increase in bone formation, density, and strength.

    Ultragenyx to Present at 39ᵗʰ Annual J.P. Morgan Healthcare Conference

    • Dr. Kakkis will present on Tuesday, January 12, 2021 at 2:50 p.m. ET. The live and archived webcast of the presentation will be accessible from the company's website at http://ir.ultragenyx.com/events.cfm

    1: Ultragenyx territories include the collaboration revenue from the North American profit share territory (U.S. and Canada) and other regions where revenue from product sales are recognized by Ultragenyx (Latin America, Turkey). This excludes the European territory revenue, which is recognized as non-cash royalty revenue since the rights were sold to Royalty Pharma in December 2019.

    About Ultragenyx

    Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

    The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx's strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

    For more information on Ultragenyx, please visit the company's website at www.ultragenyx.com.

    Forward-Looking Statements

    Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the effects from the COVID-19 pandemic on the company's clinical activities, business and operating results, risks related to reliance on third party partners to conduct certain activities on the company's behalf, uncertainty and potential delays related to clinical drug development, smaller than anticipated market opportunities for the company's products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company's future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx's products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on October 27, 2020, and its subsequent periodic reports filed with the Securities and Exchange Commission.

    Contact Ultragenyx Pharmaceutical Inc.

    Investors & Media

    Joshua Higa

    415-660-0951



    Primary Logo

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  4. Durable and Clinically Meaningful Responses Reported from Phase 1/2 Studies of DTX401 for GSDIa and DTX301 for OTC

    Phase 3 Studies for DTX401 and DTX301 to Begin in 2021

    IND for UX701 for Wilson Disease Submitted; Expect to Enter Clinic in First Half 2021 using AAV Drug Product Made by HeLa PCL Platform

    NOVATO, Calif. , Jan. 08, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, today announced positive longer-term safety and efficacy data from the first three cohorts of the ongoing Phase 1/2 studies of DTX401, an investigational adeno-associated virus (AAV) gene therapy for Glycogen Storage…

    Durable and Clinically Meaningful Responses Reported from Phase 1/2 Studies of DTX401 for GSDIa and DTX301 for OTC

    Phase 3 Studies for DTX401 and DTX301 to Begin in 2021

    IND for UX701 for Wilson Disease Submitted; Expect to Enter Clinic in First Half 2021 using AAV Drug Product Made by HeLa PCL Platform

    NOVATO, Calif. , Jan. 08, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, today announced positive longer-term safety and efficacy data from the first three cohorts of the ongoing Phase 1/2 studies of DTX401, an investigational adeno-associated virus (AAV) gene therapy for Glycogen Storage Disease Type Ia (GSDIa), and DTX301, an AAV gene therapy for ornithine transcarbamylase (OTC) deficiency. In addition, dosing is nearing completion for the prophylactic steroid cohorts in both studies. Discussions with regulatory agencies continue to progress for both programs, and Ultragenyx expects to initiate Phase 3 studies for DTX401 in the first half of 2021 and for DTX301 in the second half of 2021. The company also plans to start a seamless single-protocol Phase 1/2/3 study for UX701, an AAV gene therapy for Wilson disease.

    "We continue to see durable and clinically meaningful responses in patients in both the DTX401 and DTX301 programs. GSDIa patients treated with DTX401 demonstrate continually improved glucose metabolism with reduction or elimination of cornstarch dependence over time. OTC patients treated with DTX301 show good metabolic control after tapering or discontinuation of alternate pathway medications and protein restricted diet," said Eric Crombez, M.D., Chief Medical Officer of the Ultragenyx Gene Therapy development unit. "With the initiation of the UX701 program in Wilson disease and progression of DTX401 and DTX301 to Phase 3 as well as progress in our preclinical stage programs, we are leveraging our proprietary platforms to advance one of the broadest portfolios of gene therapy programs in the industry."

    DTX401 (GSDIa) Program

    Phase 1/2 data update: All patients (n=9) responding and demonstrating continued improvement of glucose control while reducing or eliminating cornstarch therapy

    All nine patients continue to demonstrate improved glucose control while tapering or discontinuing oral glucose replacement with cornstarch and improvements in energy metabolism pathways over the long term. Patients continue to taper the amount and frequency of cornstarch dosing with progress in eliminating overnight and daytime cornstarch doses. At the primary evaluation timepoint at Week 52, the overall mean reduction in cornstarch was 77% across all three cohorts, including two patients in Cohort 3 showing a reduction of greater than 75%. Longer term follow-up for more than two years for the three patients in Cohort 1 have shown sustained and continued cornstarch reductions with a mean reduction of 91% through weeks 104 and 120. Two patients (one each from Cohort 1 and 3) are completely off cornstarch therapy at weeks 127 and 60, respectively.

    Data collected from continuous glucose monitoring (CGM) implemented in Cohort 3 indicate that glycemic control was maintained and even improved despite the reductions in cornstarch dependence. Through Week 48, these patients had decreased cornstarch use by between 30% and 92%. Even with these substantial cornstarch reductions, the patients had a mean 10% increase in the percent of time spent in euglycemia, defined by blood glucose levels in the normal range of 60 to 120 mg/dL.

    Additionally, these reductions in cornstarch dosing have had an impact on energy metabolism and body weight. Seven of nine treated patients had decreases of 5% (5.6 kg) to 21% (10.5 kg) in bodyweight following DTX401 treatment, with a mean decrease of 12% from the mean baseline weight of 82.8 kg in these seven patients. The notable weight loss is attributed to improved glycemic control and potentially increased physical activity reported by patients.

    Interviews with patients following their Week 24 and/or Week 52 visits provide support for the study results seen to date. Patients reported improvements in both their physical and mental health. This includes increased energy and strength, supporting normalization of daily activities and weight loss, as well as greater mental acuity and reduced stress, with the latter in part noted as related to diminished fears of missing a cornstarch dose. No negative patient feedback has been received to date on their experiences with DTX401.

    The safety profile of DTX401 remains favorable; there have been no infusion-related adverse events and no treatment-related serious adverse events reported. All adverse events have been Grade 1 or 2.

    All three GSDIa patients dosed in prophylactic steroid cohort doing well with no safety issues

    All three patients in a fourth and final Phase 1/2 cohort, which utilizes prophylactic steroids, have been dosed at the same dose as Cohorts 2 and 3. There have been no safety issues through up to 11 weeks post-dosing, and all three patients are doing well and have demonstrated early reduction in daily cornstarch intake.

    Phase 3 study of DTX401 in GSDIa expected to initiate in first half 2021

    The company has completed Scientific Advice with the European Medicines Agency (EMA) and an End of Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) to discuss the Phase 2 data, the Phase 3 design, and endpoints. Based in part on this feedback, Ultragenyx plans to conduct a 48-week Phase 3 study in approximately 50 patients, randomized 1:1 to DTX401 or placebo. All patients in the study will cross over to the therapeutic arm and receive therapy at the end of the initial 48-week follow-up period.

    Based on the regulatory discussion and pending finalization, Ultragenyx intends to study as primary endpoints glycemic control by assessing the maintenance of glucose control by CGM and the reduction in cornstarch requirements. These primary endpoints will be supported by key secondary endpoints of improvement in percent of time spent in normal glucose control (60-120 mg/dL), time to hypoglycemia in controlled fasting challenge, and the GSDIa functional assessment diary signs and symptom scale. The durability of the treatment will be supported by the longer-term Phase 1/2 data and early treated Phase 3 patients. Based on the results to date, the therapeutic benefit appears to increase over time during the second year after treatment. Ultragenyx expects to initiate the study in the first half of 2021.

    DTX301 (OTC) Program

    Phase 1/2 data update: All six previous responders demonstrate durable metabolic control, including greater than two-year sustained responses

    As previously reported, six out of nine treated patients responded to DTX301 on a dose-dependent basis, including all three treated at the highest dose. The three complete responders have now been stable through 104, 130, and 156 weeks post-treatment with good ammonia control despite discontinuation of their alternative pathway medications and protein-restricted diets. The three other responders also remain stable through Weeks 52 and 130 and are either continuing to taper medications and diet or intend to continue tapering once COVID-19 restrictions are lifted and patients can be more closely followed in clinic. All responders remain in excellent clinical condition with no significant adverse events, hospitalizations, or other events related to OTC deficiency.

    There have been no infusion-related adverse events and no treatment-related serious adverse events reported in the study. All treatment-related adverse events have been Grade 1 or 2.

    Prophylactic steroid cohort: Two OTC patients dosed with no safety issues; third patient to be dosed this month

    Two of three patients have been dosed in the prophylactic steroid cohort, the final cohort in the Phase 1/2 study, at the same dose as in Cohort 3. Through up to 18 weeks post-dosing, both patients are doing well clinically with good metabolic control and without any safety issues. The third patient in the cohort, who has not yet been dosed due to delays related to COVID-19, is expected to be dosed this month.

    Phase 3 study of DTX301 in OTC expected to initiate in second half 2021

    Ultragenyx completed the initial Scientific Advice process with the EMA regarding the Phase 3 development plan and continues to have discussions with the FDA regarding the Phase 3 study of DTX301. The EOP2 meeting with the FDA had been delayed and is now scheduled to occur late in the first quarter of 2021.

    Based on regulatory feedback to date, the proposed Phase 3 study design will include approximately 50 patients, randomized 1:1 to DTX301 or placebo and followed for 48 weeks initially. The change in 24-hour ammonia levels is expected as the primary endpoint. The entry criteria will allow patients with higher baseline ammonia levels than in the Phase 1/2 study to allow sufficient power to assess the change in ammonia. The primary endpoint will be supported by the change in the rate of ureagenesis as a key secondary endpoint that evaluates the capacity to generate urea from ammonia. Additional secondary endpoints include reduction or discontinuation of scavenger medications and normalization of protein-restricted diet.

    The Phase 3 study is expected to begin dosing in the second half of 2021. Placebo patients participating in the study will receive DTX301 at the end of the initial 48-week follow-up period. The company will continue to follow patients in the ongoing Phase 1/2 study during the Phase 3 in order to augment the overall long-term data package supporting the durability of DTX301.

    Update on Dose Level Determination Method for DTX301 and DTX401

    A new droplet digital PCR (ddPCR) test method has been implemented to determine the level of genome copy (GC) titers for Ultragenyx's gene therapy candidates. This new process improves the accuracy, precision, and specificity compared to the prior quantitative PCR (qPCR) approach. As a result, the actual highest Phase 1/2 dose and planned Phase 3 dose for DTX301 is 1.7 x 10^13 GC/kg (from 1.0 x 10^13 GC/kg) and for DTX401 is 1.0 x 10^13 GC/kg (from 6.0 x 10^12 GC/kg). This change in dose designation of the same product does not represent a change in dose but a more accurate estimate of the actual GC content of the product relative to qPCR, the prior method.

    UX701 (Wilson Disease) Program using HeLa PCL Platform

    Ultragenyx submitted an Investigational New Drug (IND) application in December as planned for UX701, an AAV9 gene therapy for the treatment of Wilson Disease. The company expects to initiate a seamless single-protocol Phase 1/2/3 study in the first half of 2021. Manufacture and testing of GMP grade drug product to supply the clinical study are complete using the company's proprietary HeLa 2.0 PCL process at the 2,000 liter scale.

    Ultragenyx previously reported that UX701 has received orphan drug designation by the FDA. The European Commission has since also granted orphan drug designation for the gene therapy.

    Advancing HeLa Producer Cell Line (PCL) Platform and Programs

    Ultragenyx continues to advance the proprietary HeLa producer cell line (PCL) platform with recent HeLa 3.0 improvements. The platform enables large 2,000 liter commercial-scale manufacturing and yields high-quality product from a highly reproducible, highly scalable platform, and less expensive process.

    Breaking Ground on Gene Therapy Manufacturing Plant

    Ultragenyx recently broke ground on its new manufacturing facility to provide important internal capacity to develop and manufacture supply of the company's gene therapies for both clinical-stage and approved products. The initial 100,000 square foot facility will be able to support two independent manufacturing suites with an initial capacity of 30 runs per year and is expected to be complete in 2023.

    DTX201 / BAY 2599023 (Hemophilia A) Program Partnered with Bayer AG and Currently Manufactured in HeLa PCL System

    Updated Phase 1/2 data through three cohorts were presented at the American Society of Hematology Annual Meeting & Exposition in December 2020 for DTX201 / BAY 2599023, an AAVhu37 gene therapy in development by Bayer, using Ultragenyx's HeLa PCL platform. The data demonstrate dose-responsive and sustained FVIII levels with no evidence of loss of expression through follow-up between 40 and 80 weeks after treatment. Patients in Cohorts 2 and 3 were on FVIII prophylaxis prior to gene therapy, which they have discontinued since approximately 6 weeks after receiving treatment. No spontaneous bleeds have been reported after achieving protective FVIII levels of greater than 15 IU/dL.

    No treatment-emergent serious adverse events have been reported. ALT elevations have been observed in three patients at higher doses, which were managed with corticosteroid treatment.

    Preclinical HeLa PCL Programs Progress

    Earlier-stage preclinical programs utilizing the HeLa PCL platform continue to advance, including:

    • The collaboration with Solid Biosciences to develop new gene therapies for Duchenne muscular dystrophy using Solid's novel microdystrophin with AAV8 variants and the HeLa 3.0 platform for cost-effective manufacturing.



    • The platform-based partnership with Daiichi Sankyo Company, which provides a non-exclusive license to Ultragenyx's AAV-based gene therapy manufacturing technologies.

    About GSDIa and DTX401

    GSDIa is the most severe genetically inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies. An estimated 6,000 patients worldwide are affected by GSDIa.

    DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted Orphan Drug Designation in both the United States and Europe, and Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track designation in the United States.

    About OTC Deficiency and DTX301

    OTC deficiency, the most common urea cycle disorder, is caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. Individuals with OTC deficiency can build up excessive levels of ammonia in their blood, potentially resulting in acute and chronic neurological deficits and other toxicities. It is estimated that more than 10,000 people are affected by OTC deficiency worldwide, of whom approximately 80 percent are classified as late-onset and represent a clinical spectrum of disease severity. In the late-onset form of the disease, elevated ammonia can lead to significant medical issues for patients. Neonatal onset disease occurs only in males, presents as severe disease, and can be fatal at an early age. Approved therapies, which must be taken multiple times a day for the patient's entire life, do not eliminate the risk of future metabolic crises. Currently, the only curative approach is liver transplantation.

    DTX301 is an investigational AAV type 8 gene therapy designed to deliver stable expression and activity of OTC following a single intravenous infusion. It has been shown in preclinical studies to normalize levels of urinary orotic acid, a marker of ammonia metabolism. DTX301 was granted Orphan Drug Designation in both the United States and Europe.

    About Wilson Disease and UX701

    Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be treated by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and severe side effects. Wilson disease affects more than 50,000 individuals in the developed world.

    UX701 is an investigational AAV type 9 gene therapy designed to deliver stable expression of a truncated version of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to normalize copper trafficking and excretion from the body. UX701 was granted Orphan Drug Designation in the United States and European Union.

    About Ultragenyx

    Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

    The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx's strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency and ensuring majority access to its therapies for patients who can benefit.

    For more information on Ultragenyx, please visit the company's website at www.ultragenyx.com.

    Ultragenyx Forward-Looking Statements

    Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the effects from the COVID-19 pandemic on the company's clinical activities, business and operating results, risks related to reliance on third party partners to conduct certain activities on the company's behalf, uncertainty and potential delays related to clinical drug development, smaller than anticipated market opportunities for the company's products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company's future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx's products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on October 27, 2020, and its subsequent periodic reports filed with the Securities and Exchange Commission.

    Contact Ultragenyx

    Investors & Media

    Joshua Higa

    (415) 475-6370

     



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  5. NOVATO, Calif., Jan. 05, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, today announced that Emil D. Kakkis, M.D., Ph.D., the company's Chief Executive Officer and President, will present at the 39th Annual J.P. Morgan Virtual Healthcare Conference on Tuesday, January 12, 2021 at 2:50 pm EST.

    The live and archived webcast of the presentation will be accessible from the company's website at http://ir.ultragenyx.com/events.cfm. The replay of the webcast will be available for 30 days.

    About Ultragenyx

    Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for…

    NOVATO, Calif., Jan. 05, 2021 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, today announced that Emil D. Kakkis, M.D., Ph.D., the company's Chief Executive Officer and President, will present at the 39th Annual J.P. Morgan Virtual Healthcare Conference on Tuesday, January 12, 2021 at 2:50 pm EST.

    The live and archived webcast of the presentation will be accessible from the company's website at http://ir.ultragenyx.com/events.cfm. The replay of the webcast will be available for 30 days.

    About Ultragenyx

    Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

    The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx's strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

    For more information on Ultragenyx, please visit the company's website at www.ultragenyx.com.

    Contact Ultragenyx Pharmaceutical Inc.

    Investors & Media

    Joshua Higa

    415-660-0951



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