FULC Fulcrum Therapeutics Inc.

7.31
-0.17  -2%
Previous Close 7.48
Open 7.38
52 Week Low 7.01
52 Week High 18.375
Market Cap $238,887,847
Shares 32,679,596
Float 17,772,196
Enterprise Value $95,035,846
Volume 184,491
Av. Daily Volume 181,245
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Upcoming Catalysts

Drug Stage Catalyst Date
FTX-6058
Sickle Cell Disease
Phase 1
Phase 1
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Drug Pipeline

Drug Stage Notes
Losmapimod (ReDUX4)
Facioscapulohumeral muscular dystrophy (FSHD)
Phase 2b
Phase 2b
Phase 2b trial did not meet primary endpoint. Intends to discuss pathway forward with FDA 2H 2021.
Losmapimod
Facioscapulohumeral muscular dystrophy (FSHD)
Phase 2
Phase 2
Phase 2 open-label trial has completed enrolment - noted March 5, 2020.
Losmapimod
COVID-19
Phase 3
Phase 3
Phase 3 trial to be discontinued - March 4, 2021.

Latest News

    • Primary endpoint, change in DUX4-driven gene expression which was included as an experimental biomarker, was not met
    • Losmapimod showed statistically significant* (p0.05) and clinically relevant benefit across multiple structural, functional and patient reported endpoints
      • Decreased Muscle Fat Infiltration
      • Improved Reachable Workspace
      • Improved Patient Global Impression of Change
    • Losmapimod was well tolerated with no treatment related discontinuations or treatment related serious adverse events
    • Positive benefit/risk supports losmapimod's potential to be a transformative therapy for the treatment of FSHD
    • Fulcrum expects to engage with health authorities, including the FDA, in H2 2021
    • Fulcrum to host conference call today at 8:00am ET; Full data
    • Primary endpoint, change in DUX4-driven gene expression which was included as an experimental biomarker, was not met
    • Losmapimod showed statistically significant* (p<0.05) and clinically relevant benefit across multiple structural, functional and patient reported endpoints
      • Decreased Muscle Fat Infiltration
      • Improved Reachable Workspace
      • Improved Patient Global Impression of Change
    • Losmapimod was well tolerated with no treatment related discontinuations or treatment related serious adverse events
    • Positive benefit/risk supports losmapimod's potential to be a transformative therapy for the treatment of FSHD
    • Fulcrum expects to engage with health authorities, including the FDA, in H2 2021
    • Fulcrum to host conference call today at 8:00am ET; Full data to be presented at FSHD International Research Congress today at 1:33pm ET

    CAMBRIDGE, Mass., June 24, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced results from the company's Phase 2b trial, ReDUX4, in people with facioscapulohumeral muscular dystrophy (FSHD). Results being presented with losmapimod at the FSHD International Research Congress today showed clinically relevant and statistically significant* benefits versus placebo on multiple measures of structural and functional FSHD disease progression and patient reported outcomes at 48 weeks. Losmapimod was generally well-tolerated, with no drug-related serious adverse events reported. Consistent with the previously reported interim analyses the primary endpoint was not met. Changes in DUX4-driven gene expression, which were included in the trial as an experimental biomarker endpoint, could not be demonstrated, the Company believes due to several technical and biologic variables with the endpoint. Based on today's results, the Company plans to meet with health authorities, including the U.S. Food and Drug Administration (FDA), in the second half of 2021 to determine the regulatory path for losmapimod in FSHD.

    "These results provide strong support that treatment with losmapimod has a meaningful clinical benefit in relevant measures of FSHD disease progression, despite the challenges of measuring DUX4," said Rabi Tawil, MD, ReDUX4 principal investigator and professor of neurology at University of Rochester Medical Center. "I am enthusiastic about the potential for losmapimod to offer meaningful improvements in preserving muscle function and patient quality of life."

    "People living with FSHD experience a progressive loss of function," said Fran Sverdrup, Ph.D., FSHD parent and FSHD researcher and associate professor of biochemistry and molecular biology at Saint Louis University. "The ReDUX4 trial with losmapimod is the first trial to demonstrate a positive benefit in several measures of FSHD, including slower disease progression and patient reported improvement over time. I am excited about today's findings and hopeful for the many patients who suffer from this devastating disease."

    *Nominally statistically significant means the p-value of a test is ≤ 0.05, calculated without regard to the test procedures in the trial's statistical analysis plan.

    FSHD is a serious, rare, progressive and disabling disease for which there are no approved treatments. FSHD is characterized by muscle degeneration and fat infiltration, initially affecting movement of the face and eventually the arms, trunk and legs. Disease progression results in accumulation of disability, with many patients ultimately becoming dependent upon the use of a wheelchair for daily mobility. Impact on patients includes decreased ability to perform activities of daily living, maintain independence, and lost ability to function or work.

    "We are thrilled with the data reported from ReDUX4," said Bryan Stuart, Fulcrum's president and chief executive officer. "These results showing consistent reduction in fat infiltration and correlating benefit on multiple measures with losmapimod represent a major advance for the potential treatment of this devastating disease. Our broader molecular insights confirm the variability in DUX4 expression in skeletal muscle and can play an important role in guiding future research, while our structural and functional results show statistically significant* differences in several novel and established measures of disease progression between losmapimod and placebo at 48 weeks. I would like to thank the patients, caregivers and clinicians who participated in ReDUX4 for their important contributions and dedication."

    "These structural, functional, and patient-reported results observed in ReDUX4 are unprecedented in FSHD," continued Mr. Stuart.   "In particular, we are pleased by the fact that we observed these results within a 48-week time period. We plan to meet with health authorities, including the FDA, in the second half of the year to determine the regulatory path for losmapimod in FSHD."

    About ReDUX4

    ReDUX4 was an equally randomized, double-blind, placebo-controlled multicenter international Phase 2b clinical trial in 80 participants with FSHD designed to investigate the efficacy and safety of oral administration of losmapimod 15 mg twice per day. As a result of the COVID-19 pandemic, Fulcrum announced in May 2020 that the trial had been extended from 24 to 48 weeks to ensure the safety of participation during the pandemic. This extension also enabled the collection of safety and efficacy data over a longer time period. Over the course of the trial, there were three discontinuations, none of which were assessed to be related to study drug. Following the completion of the trial, 99% of eligible participants elected to continue in the Open Label Extension trial.

    The following data describe key results from the primary, secondary and exploratory endpoints showing clinically relevant and nominally statistically significant benefits versus placebo on multiple measures of structural and functional FSHD disease progression and patient reported outcomes at 48 weeks.

    DUX4-Driven Gene Expression

    The primary endpoint, change from baseline in DUX4-driven gene expression in affected skeletal muscle at Week 16 or Week 36, was not met. Reduction in DUX4-driven gene expression was included as an experimental biomarker endpoint because the Company believed it would correlate with downstream clinical improvements in patients with FSHD.

    Losmapimod reduced DUX4-driven gene expression in preclinical in vivo and in vitro experiments.  ReDUX4 was the first interventional clinical trial to test whether changes in intramuscular DUX4-driven gene expression could be assessed in patients with FSHD.  FSHD is a highly heterogenous disease, and DUX4 expression in each patient's muscle is heterogeneous and stochastic.  In the losmapimod treatment arm, repeat muscle needle biopsies at Week 16 or 36 did not demonstrate a difference in DUX4 activity, including from the prespecified subgroup analyses by DUX4-expressing quartiles. The ability to detect changes in DUX4-driven gene expression was confounded by significant variability across biopsies at baseline and upon repeat biopsy in both the placebo and losmapimod groups. The Company believes the sources of the variability include the stochastic nature of DUX4 expression in which biopsy samples showed a dynamic state of expression (over 1,000-fold variation), the scarcity of DUX4 positive myonuclei (~1/1000), as well as the relative imprecision in the needle biopsy procedure across multiple clinical trial sites.

    While a reduction in the molecular biomarker of DUX4-driven gene expression was not observed, the Company believes that benefits on muscle health, function and patient benefit observed in the clinical trial were associated with a reduction of DUX4-driven gene expression.  

    Muscle Fat Infiltration (MFI)

    • Losmapimod-treated participants showed decreased progression in the treatment efficacy composite measure of muscle fat infiltration as measured in intermediate muscles, those most likely to change (p=0.01*). Normal appearing muscles appeared to be preserved in the losmapimod group versus placebo based on a post hoc analysis.

    Muscle fat infiltration is a measure of diffuse fatty infiltration in lean muscle tissue that is correlated with disease severity in FSHD.   Participants in ReDUX4 trial were assessed with a quantitative whole body musculoskeletal magnetic resonance imaging (WB-MSK-MRI) which provides a holistic evaluation of skeletal musculature with the ability to volumetrically measure fat replacement of skeletal muscle in FSHD. Prior clinical trials have demonstrated that the amount of muscle fat replacement correlates with muscle function in many neuromuscular diseases, including FSHD. Furthermore, changes in fat content are correlated with changes in function. Taken together, ReDUX4 demonstrated that this MRI technology has sufficient sensitivity to detect FSHD relevant disease progression.  

    Reachable Workspace (RWS)

    • Treatment with losmapimod was shown to slow the rate of decline and improve accessible surface area in Reachable Workspace (RWS) measures (p<0.05*).

    RWS is a measure of upper extremity range of motion and function. Prior studies have shown that RWS correlates with changes in the ability of patients to independently perform activities of daily living. Based on published results, reachable workspace is an important measure of disability. The disease tends to progress from the upper body down, and loss of shoulder movement leads to loss of mobility. Participants in the losmapimod group showed improvements of up to 1.5% from baseline in the accessible surface area when using a 500g weight on their wrist compared to placebo. Participants in the placebo group were able to access 2 to 4% less total surface area (with and without 500g weights) measured by RWS after 48 weeks.

    Patient Global Impression of Change (PGIC)

    • Participants reported feeling better when treated with losmapimod compared to placebo through the Patient Global Impression of Change assessment (p=0.02*)

    PGIC, a measure of self-reported change in how a patient feels and functions, showed that participants were able to recognize improvements after 48 weeks of treatment. More participants in the losmapimod group reported improvement at 48 weeks compared to placebo. Four times more losmapimod participants reported improvement over time as compared to participants treated with placebo. Importantly, fewer losmapimod participants reported worsening as compared to placebo, and no losmapimod participants reported being "much worse" as compared to more than 13% of placebo participants, who reported that their disease had become "much worse."

    Additional Secondary and Exploratory Endpoints, Pharmacokinetics and Target Engagement

    Additional secondary and exploratory endpoints measuring disease progression and function demonstrated differences between losmapimod and placebo at week 48. In a post hoc analysis, dynamometry, which measures muscle strength, demonstrated that participants in the losmapimod group showed non-statistically significant trends of slower progression, as well as meaningful improvements (12-27%) in the strength of bilateral shoulder abductors and ankle dorsiflexors, two muscle groups particularly affected in FSHD, compared to placebo. Functional scales including RWS and TUG showed improvements in limb function consistent with dynamometry results. Two recently designed scales, (FSHD TUG, and FSHD Health Index) did not demonstrate changes from baseline in either group or differences between losmapimod and placebo groups, suggesting that these tests are not sensitive to change over the 48-week time period. Motor function measure also showed no changes in either group or differences between the groups over 48 weeks. There was no difference in muscle fat fraction or lean muscle volume between losmapimod and placebo groups at 48 weeks in intermediate muscles. The Company believes it may observe statistically significant differences in these measures with more time. Additional MRI data will be presented during the IRC meeting. Fulcrum will continue to analyze data from each endpoint to determine their viability for future trials. Blood concentrations and target engagement in muscle were consistent with previous studies and were within the expected range for clinical efficacy.

    Overall Safety and Tolerability

    Safety and tolerability data were consistent with previously reported results with no drug-related serious adverse events reported. Losmapimod was generally well-tolerated and the majority of treatment emergent adverse events were deemed unlikely related or not related to study drug by the investigator. There were three serious adverse events (post-op wound infection, alcohol poisoning and a suicide attempt) reported in two participants in the losmapimod group, each assessed as unrelated to losmapimod. There were no deaths or discontinuations due to adverse events. Losmapimod has now been evaluated in over 3,600 subjects in clinical trials across multiple indications, including FSHD.

    Fulcrum will present detailed results from the ReDUX4 trial during the FSHD International Research Congress today at 1:33pm ET.

    Conference Call Information

    Fulcrum will host a conference call and webcast today at 8:00 am ET to discuss the ReDUX4 data. The webcast will be accessible through the Investor Relations section of Fulcrum's website at www.fulcrumtx.com. Following the live webcast, an archived replay will also be available.

    Dial-in Number

    U.S./Canada Dial-in Number: 800-527-6973

    International Dial-in Number: 470-495-9162

    Conference ID: 3005948

    Replay Dial-in Number: 855-859-2056

    Replay International Dial-in Number: 404-537-3406

    Conference ID: 3005948

    About FSHD

    FSHD is a serious, rare, progressive and disabling disease for which there are no approved treatments. FSHD is characterized by muscle degeneration and fat infiltration, initially affecting movement of the face and eventually the arms, trunk and legs. Disease progression results in accumulation of disability, with many patients ultimately becoming dependent upon the use of a wheelchair for daily mobility. Impact on patients includes decreased ability to perform activities of daily living, maintain independence, and lost ability to function or work.

    FSHD is caused by mis-expression of DUX4 in skeletal muscle, resulting in the presence of DUX4 proteins that are toxic to muscle tissue. Normally, DUX4-driven gene expression is limited to early embryonic development, after which time the DUX4 gene is silenced. In people with FSHD, the DUX4 gene is turned "on" as a result of a genetic mutation. The result is death of muscle and its replacement by fat, leading to skeletal muscle weakness and progressive disability. There are no approved therapies for FSHD, one of the most common forms of muscular dystrophy, with an estimated patient population of 16,000 to 38,000 in the United States alone.

    About Losmapimod

    Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor that was exclusively in-licensed from GSK by Fulcrum Therapeutics following Fulcrum's discovery of the role of p38α/β inhibitors in the reduction of DUX4 expression and an extensive review of known compounds. Utilizing its proprietary product engine, FulcrumSeek, Fulcrum discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD. Although losmapimod has never previously been explored in muscular dystrophies, it has been evaluated in more than 3,600 subjects in clinical trials across multiple other indications, including in several Phase 2 trials and a Phase 3 trial. No safety signals were attributed to losmapimod in any of these trials. Losmapimod has been granted U.S. Food and Drug Administration (FDA) Fast Track designation and Orphan Drug Designation for the treatment of FSHD.

    About Fulcrum Therapeutics

    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum's proprietary product engine, FulcrumSeek, identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD). Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta thalassemia into Phase 1 clinical development.

    Please visit www.fulcrumtx.com.

    Forward-Looking Statements

    This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Company's product candidates, the potential advantages and therapeutic potential of the Company's product candidates planned meetings with regulatory agencies and availability of clinical trial data. All statements, other than statements of historical facts, contained in this press release, including statements regarding the Company's strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum's ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the Company's product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod and its other product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in the Company's most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof and should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

    Contact:

    Investors:

    Christi Waarich

    Director, Investor Relations and Corporate Communications



    617-651-8664

    Stephanie Ascher

    Stern Investor Relations, Inc.



    212-362-1200

    Media:

    Kaitlin Gallagher

    Berry & Company Public Relations



    212-253-8881



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  1. CAMBRIDGE, Mass., June 21, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced multiple presentations at the 28th Annual FSHD Society International Research Congress (IRC).

    June 24, 2021 IRC Virtual Presentations

    • 10:43 am ET - Use of snRNA-seq to characterize the skeletal muscle microenvironment during pathogenesis in FSHD
    • 1:33 pm ET - A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects with Facioscapulohumeral Muscular Dystrophy (FSHD) with Open Label Extension (OLE): ReDUX4
    • 1:58 pm ET

    CAMBRIDGE, Mass., June 21, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced multiple presentations at the 28th Annual FSHD Society International Research Congress (IRC).

    June 24, 2021 IRC Virtual Presentations

    • 10:43 am ET - Use of snRNA-seq to characterize the skeletal muscle microenvironment during pathogenesis in FSHD
    • 1:33 pm ET - A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects with Facioscapulohumeral Muscular Dystrophy (FSHD) with Open Label Extension (OLE): ReDUX4
    • 1:58 pm ET - Fulcrum Panel Q&A
    • Poster - Evaluating DUX4 Activity in a Phase 2, Randomized, Double-Blind, Placebo-Controlled,​ 48-Week Study of the Efficacy and Safety of Losmapimod in Subjects with FSHD
    • Poster - Quantitative Muscle Analysis in FSHD Using Whole-Body MRI: Composite Muscle Measurements for Cross-Sectional Analysis

    The sessions will be available to registered conference attendees. The posters and presentation will also be made available in the "Events & Presentations" section of fulcrumtx.com.

    Management will host a conference call on June 24, 2021 at 8:00 am ET to discuss the results of the ReDUX4 trial.

    Conference Call Details

    Dial-in Number

    U.S./Canada Dial-in Number: 800-527-6973

    International Dial-in Number: 470-495-9162

    Conference ID: 3005948

    Replay Dial-in Number: 855-859-2056

    Replay International Dial-in Number: 404-537-3406

    Conference ID: 3005948

    An audio webcast will be accessible through the Investor Relations section of the company's website https://ir.fulcrumtx.com/events-and-presentations. Following the live webcast, an archived replay will also be available.

    About FSHD

    FSHD is a serious, rare, progressive and disabling disease for which there are no approved treatments. FSHD is characterized by muscle degeneration and fat infiltration, initially affecting movement of the face and eventually the arms, trunk and legs. Disease progression results in accumulation of disability, with many patients ultimately becoming dependent upon the use of a wheelchair for daily mobility. Impact on patients includes decreased ability to perform activities of daily living, maintain independence, and lost ability to function or work.

    FSHD is caused by mis-expression of DUX4 in skeletal muscle, resulting in the presence of DUX4 proteins that are toxic to muscle tissue. Normally, DUX4-driven gene expression is limited to early embryonic development, after which time the DUX4 gene is silenced. In people with FSHD, the DUX4 gene is turned "on" as a result of a genetic mutation. The result is death of muscle and its replacement by fat, leading to skeletal muscle weakness and progressive disability. There are no approved therapies for FSHD, one of the most common forms of muscular dystrophy, with an estimated patient population of 16,000 to 38,000 in the United States alone.

    About Losmapimod

    Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor that was exclusively in-licensed from GSK by Fulcrum Therapeutics following Fulcrum's discovery of the role of p38α/β inhibitors in the reduction of DUX4 expression and an extensive review of known compounds. Utilizing its proprietary product engine, FulcrumSeek, Fulcrum discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD. Although losmapimod has never previously been explored in muscular dystrophies, it has been evaluated in more than 3,600 subjects in clinical trials across multiple other indications, including in several Phase 2 trials and a Phase 3 trial. No safety signals were attributed to losmapimod in any of these trials. Losmapimod has been granted U.S. Food and Drug Administration (FDA) Fast Track designation and Orphan Drug Designation for the treatment of FSHD.

    About Fulcrum Therapeutics

    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum's proprietary product engine, FulcrumSeek, identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD). Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta-thalassemia into Phase 1 clinical development.

    Please visit www.fulcrumtx.com.

    Forward-Looking Statements

    This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties, and other important factors, in the Company's most recent filings with the Securities and Exchange Commission.

    Contact:

    Investors:

    Christi Waarich

    Director, Investor Relations and Corporate Communications



    617-651-8664

    Stephanie Ascher

    Stern Investor Relations, Inc.



    212-362-1200

    Media:

    Kaitlin Gallagher

    Berry & Company Public Relations



    212-253-8881



    Primary Logo

    View Full Article Hide Full Article
  2. CAMBRIDGE, Mass., May 12, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to losmapimod for the potential treatment of facioscapulohumeral muscular dystrophy (FSHD).

    "There are no approved therapies to treat patients with FSHD, and losmapimod is currently the only drug in clinical development for this serious and debilitating disease," said Judith Dunn, Ph.D., Fulcrum's president of research and development. "We are pleased that the FDA has granted Fast Track designation, which we believe demonstrates…

    CAMBRIDGE, Mass., May 12, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to losmapimod for the potential treatment of facioscapulohumeral muscular dystrophy (FSHD).

    "There are no approved therapies to treat patients with FSHD, and losmapimod is currently the only drug in clinical development for this serious and debilitating disease," said Judith Dunn, Ph.D., Fulcrum's president of research and development. "We are pleased that the FDA has granted Fast Track designation, which we believe demonstrates the potential for losmapimod to address unmet medical needs for people living with FSHD."

    Fast Track Designation is intended to facilitate development and expedite the review of drugs that treat serious conditions so an approved product can reach the market expeditiously. It enables the company to have more frequent interactions with the FDA throughout the drug development process and allows for eligibility for priority review and accelerated approval in certain cases, as well as a rolling review.

    Fulcrum is on track to report full data from ReDUX4, a Phase 2b randomized, double-blind, placebo-controlled trial of losmapimod in FSHD patients, at the virtual FSHD International Research Congress taking place June 24-25, 2021. Data will include the primary endpoint, reduction from baseline of DUX4-driven gene expression, as well as a pre-specified sensitivity analysis assessing biopsies with the highest pre-treatment level of DUX4-driven gene expression. Additional data to be reported include secondary endpoints evaluating disease progression via skeletal muscle MRI, exploratory endpoints assessing muscle function measures and patient reported outcomes.

    Losmapimod previously received Orphan Drug Designation for FSHD.

    About Losmapimod

    Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor that was exclusively in-licensed from GSK by Fulcrum Therapeutics following Fulcrum's discovery of the role of p38α/β inhibitors in the reduction of DUX4 expression and an extensive review of known compounds. Utilizing its internal product engine, Fulcrum discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD. Although losmapimod has never previously been explored in muscular dystrophies, it has been evaluated in more than 3,600 subjects in clinical trials across FSHD and multiple other indications, including in several Phase 2 trials and a Phase 3 trial. No safety signals were attributed to losmapimod in any of these trials. Fulcrum is currently conducting Phase 2 trials investigating the safety, tolerability, and efficacy of losmapimod to treat the root cause of FSHD.

    About Fulcrum Therapeutics

    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum's proprietary product engine identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD). Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta-thalassemia into Phase 1 clinical development.

    Please visit www.fulcrumtx.com.

    Forward-Looking Statements

    This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Company's product candidates, the potential advantages and therapeutic potential of Fulcrum's product candidates and availability of clinical trial data. All statements, other than statements of historical facts, contained in this press release, including statements regarding the Company's strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum's ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the Company's product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, FTX-6058 and its other product candidates; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in the Company's most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof and should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

    Contact:

    Investors:

    Christi Waarich

    Director, Investor Relations and

    Corporate Communications

    617-651-8664

    Stephanie Ascher

    Stern Investor Relations, Inc.



    212-362-1200

    Media:

    Kaitlin Gallagher

    Berry & Company Public Relations



    212-253-8881



    Primary Logo

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  3. CAMBRIDGE, Mass., May 07, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced that management will present a corporate overview at the BofA Securities 2021 Virtual Health Care Conference on Thursday, May 13, 2021 at 11:00 a.m. ET.

    A live audio webcast will be available through the Investor Relations section of the Fulcrum website at https://ir.fulcrumtx.com/events-and-presentations. An archived replay will be available on the Company's website for 90 days.

    About Fulcrum Therapeutics
    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients…

    CAMBRIDGE, Mass., May 07, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced that management will present a corporate overview at the BofA Securities 2021 Virtual Health Care Conference on Thursday, May 13, 2021 at 11:00 a.m. ET.

    A live audio webcast will be available through the Investor Relations section of the Fulcrum website at https://ir.fulcrumtx.com/events-and-presentations. An archived replay will be available on the Company's website for 90 days.

    About Fulcrum Therapeutics

    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum's proprietary product engine identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD). Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta-thalassemia into Phase 1 clinical development.

    Please visit www.fulcrumtx.com.

    Contact:

    Christi Waarich

    Director, Investor Relations

    and Corporate Communications

    617-651-8664



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  4. On track to present data from Phase 2b ReDUX4 trial with losmapimod in facioscapulohumeral muscular dystrophy (FSHD) at virtual FSHD International Research Congress in June 2021

    On track to report data from Phase 1 trial in healthy adult volunteers with FTX-6058 for sickle cell disease in mid-2021

    Conference call scheduled for 8:00 a.m. ET today

    CAMBRIDGE, Mass., May 06, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today provided a business update and reported financial results for the first quarter of 2021.

    "Fulcrum has continued to make great progress in advancing our…

    On track to present data from Phase 2b ReDUX4 trial with losmapimod in facioscapulohumeral muscular dystrophy (FSHD) at virtual FSHD International Research Congress in June 2021

    On track to report data from Phase 1 trial in healthy adult volunteers with FTX-6058 for sickle cell disease in mid-2021

    Conference call scheduled for 8:00 a.m. ET today

    CAMBRIDGE, Mass., May 06, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (NASDAQ:FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today provided a business update and reported financial results for the first quarter of 2021.

    "Fulcrum has continued to make great progress in advancing our business and progressing our pipeline in the first quarter," said Bryan E. Stuart, president and chief executive officer. "We are on track to report data from ReDUX4 in FSHD later this quarter. Our Phase 1 trial in healthy adult volunteers with FTX-6058 for sickle cell disease continues to move forward with the initiation of the multiple ascending dose cohort. Our team continues to optimize the potential of FulcrumSeek™, our proprietary product engine, driven by our focus on the patient and our ability to rapidly identify novel, high quality targets that modulate the root cause of genetically defined rare diseases. In addition, we have expanded our leadership team to include Dr. Judith Dunn, President of Research and Development, and today announced that Dr. Chris Morabito has been appointed Chief Medical Officer. With these important advances and cash runway that takes us into the fourth quarter of 2022, we believe we are well positioned to continue to build on our momentum to bring important therapies to patients with genetically defined rare diseases."

    Recent Business Highlights

    • On track to present data from ReDUX4, a Phase 2b trial of losmapimod, a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor, in FSHD at the virtual FSHD International Research Congress taking place June 24-25, 2021.
      • Data will include the primary endpoint, reduction from baseline of DUX4-driven gene expression, as well as a pre-specified sensitivity analysis assessing biopsies with the highest pre-treatment level of DUX4-driven gene expression. Additional data to be reported include secondary endpoints evaluating disease progression via skeletal muscle MRI, exploratory endpoints assessing muscle function measures and patient reported outcomes.
      • Continued evaluation of the Phase 2 Open Label Study.
    • On track to report data from the Phase 1 trial in healthy adult volunteers with FTX-6058 in development for sickle cell disease (SCD) in mid-2021, and to begin dosing patients with SCD in a clinical trial by year end.
      • FTX-6058, a highly potent small molecule EED inhibitor, is designed to induce expression of fetal hemoglobin (HbF) in red blood cells following oral administration to compensate for the mutated adult hemoglobin associated with hemoglobinopathies, including SCD and beta-thalassemia.
      • Preclinical data generated in CD34+ cells from healthy and SCD donors with FTX-6058 showed an increase in HbF levels up to approximately 30% of total hemoglobin, indicating the potential to have a significant impact on patients with sickle cell disease.
      • US patent 10,973,805 issued, providing composition of matter coverage for FTX-6058 until 2040.
    • Multiple scientific meeting presentations
      • Presented new data related to the use of imaging biomarkers and clinical outcome assessments for FSHD at the virtual Muscular Dystrophy Association Clinical and Scientific Conference. Presentations included development of the whole-body musculoskeletal MRI (WB-MSK-MRI) protocol. Data showed that WB-MSK-MRI can capture heterogeneity and provide important information about disease severity. Meaningful composite MRI measurements demonstrated correlation with relevant FSHD clinical endpoints.
      • Presented the medicinal chemistry strategy for FTX-6058 at the First Time Disclosure Session at the American Chemical Society (ACS) Spring 2021 National Meeting. The presentation included initial pharmacokinetic data from the single ascending dose cohort of the Phase 1 trial in healthy adult volunteers.
    • Advanced FulcrumSeek discovery efforts and strategic collaborations with Acceleron and MyoKardia, a wholly owned subsidiary of Bristol-Myers Squibb Company.
    • Senior management updates:
      • CSO transition: On January 19, 2021, Fulcrum announced that Christopher Moxham, Ph.D. was promoted to chief scientific officer and Owen Wallace, Ph.D. stepped down from his role as chief scientific officer, each effective February 5, 2021. Dr. Wallace was appointed to Fulcrum's Scientific Advisory Board.
      • CEO transition: On March 4, 2021, Fulcrum announced that Bryan E. Stuart was promoted to president and chief executive officer and was appointed to Fulcrum's Board of Directors following the retirement of Robert J. Gould, Ph.D., each effective March 31, 2021. Dr. Gould continues to serve on Fulcrum's Board and was appointed to the Scientific & Technology committee.
      • President R&D: On March 24, 2021, Fulcrum announced that Judith A. Dunn, Ph.D. was appointed President of Research and Development, effective April 1, 2021.
      • Chief Medical Officer: On May 6, 2021, Fulcrum announced that Christopher J. Morabito, M.D. has been appointed Chief Medical Officer, effective May 10, 2021.

    First Quarter 2021 Financial Results

    • Cash Position: As of March 31, 2021, cash, cash equivalents, and marketable securities were $143.9 million, as compared to $112.9 million as of December 31, 2020. Based on current plans, the company expects that its existing cash, cash equivalents, and marketable securities will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2022.
    • Collaboration Revenues: Collaboration revenue was $4.8 million for the first quarter of 2021, as compared to $0.8 million for the first quarter of 2020. The increase in collaboration revenue was due to the execution of the company's collaboration and license agreement with MyoKardia in July 2020, as well as due to an increase in collaboration revenue associated with the company's collaboration and license agreement with Acceleron.
    • R&D Expenses: Research and development expenses were $16.3 million for the first quarter of 2021, as compared to $14.5 million for the first quarter of 2020. The increase of $1.8 million was primarily due to increased costs to support the company's ongoing and planned clinical trials.
    • G&A Expenses: General and administrative expenses were $5.5 million for the first quarter of 2021, as compared to $5.1 million for the first quarter of 2020. The increase of $0.4 million was primarily due to increased employee-compensation costs to support the growth of the organization, including increased stock-based compensation expense.
    • Net Loss: Net loss was $17.0 million for the first quarter of 2021, as compared to a net loss of $18.5 million for the first quarter of 2020.

    Conference Call and Webcast

    Fulcrum Therapeutics, Inc. will host a conference call and webcast today at 8:00 a.m. ET to discuss the Company's first quarter 2021 recent business highlights and financial results. The webcast will be accessible through the Investor Relations section of Fulcrum's website at www.fulcrumtx.com. Following the live webcast, an archived replay will also be available.

    Dial-in Number

    U.S./Canada Dial-in Number: 800-527-6973

    International Dial-in Number: 470-495-9162

    Conference ID: 5767008

    Replay Dial-in Number: 855-859-2056

    Replay International Dial-in Number: 404-537-3406

    Conference ID: 5767008

    About FSHD

    FSHD is characterized by progressive skeletal muscle loss that initially causes weakness in muscles in the face, shoulders, arms and trunk, and progresses to weakness throughout the lower body. Skeletal muscle weakness results in significant physical limitations, including an inability to smile and difficulty using arms for activities, with many patients ultimately becoming dependent upon the use of a wheelchair for daily mobility.

    FSHD is caused by mis-expression of DUX4 in skeletal muscle, resulting in the presence of DUX4 proteins that are toxic to muscle tissue. Normally, DUX4-driven gene expression is limited to early embryonic development, after which time the DUX4 gene is silenced. In people with FSHD, the DUX4 gene is turned "on" as a result of a genetic mutation. The result is death of muscle and its replacement by fat, leading to skeletal muscle weakness and progressive disability. There are no approved therapies for FSHD, one of the most common forms of muscular dystrophy, with an estimated patient population of 16,000 to 38,000 in the United States alone.

    About Losmapimod

    Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor that was exclusively in-licensed from GSK by Fulcrum Therapeutics following Fulcrum's discovery of the role of p38α/β inhibitors in the reduction of DUX4 expression and an extensive review of known compounds. Utilizing its internal product engine, Fulcrum discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD. Losmapimod has been evaluated in more than 3,600 subjects in clinical research across multiple indications, including in several Phase 2 trials and a large Phase 3 trial in acute myocardial infarction. No safety signals were attributed to losmapimod in any of these trials. In 2020, the company received U.S. and European Orphan Drug Designation for losmapimod for the treatment of FSHD. Fulcrum is currently conducting Phase 2 trials investigating the safety, tolerability, and efficacy of losmapimod to treat the root cause of FSHD.

    About Sickle Cell Disease

    Sickle cell disease (SCD) is a genetic disorder of the red blood cells caused by a mutation in the HBB gene. This gene encodes a protein that is a key component of hemoglobin, a protein complex whose function is to transport oxygen in the body. The result of the mutation is less efficient oxygen transport and the formation of red blood cells that have a sickle shape. These sickle shaped cells are much less flexible than healthy cells and can block blood vessels or rupture cells. SCD patients typically suffer from serious clinical consequences, which may include anemia, pain, infections, stroke, heart disease, pulmonary hypertension, kidney failure, liver disease and reduced life expectancy.

    About FTX-6058

    FTX-6058 is a highly potent small molecule inhibitor of Embryonic Ectoderm Development (EED) capable of inducing robust HbF protein expression in cell and murine models. Fulcrum believes the pharmacokinetics and human dose simulations support that FTX-6058 may be given as a once daily oral compound. The validation of EED as a target for sickle cell disease and the discovery of FTX-6058 as a novel HbF-inducing small molecule were conducted using Fulcrum's proprietary product engine. Preclinical data with FTX-6058 showed an increase in HbF levels up to approximately 30% of total hemoglobin. Fulcrum is conducting a Phase 1 trial with FTX-6058 in healthy adult volunteers.

    About Fulcrum Therapeutics

    Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum's proprietary product engine identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD). Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta-thalassemia into Phase 1 clinical development.

    Please visit www.fulcrumtx.com.

    Forward-Looking Statements

    This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Company's product candidates, the potential advantages and therapeutic potential of Fulcrum's product candidates, initiation and enrollment of clinical trials and availability of clinical trial data, and the Company's ability to fund its operations with cash on hand. All statements, other than statements of historical facts, contained in this press release, including statements regarding the Company's strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum's ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the Company's product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, FTX-6058 and its other product candidates; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in the Company's most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof and should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.



    Fulcrum Therapeutics, Inc.

    Selected Consolidated Balance Sheet Data

    (In thousands)

    (Unaudited)

     March 31,

    2021
      December 31,

    2020
     
    Cash, cash equivalents, and marketable securities$143,856  $112,914 
    Working capital(1) 124,356   92,785 
    Total assets 156,476   129,577 
    Total stockholders' equity 127,754   95,181 

    (1)    We define working capital as current assets minus current liabilities.



    Fulcrum Therapeutics, Inc.

    Consolidated Statements of Operations

    (In thousands, except per share data)

    (Unaudited)

     Three Months Ended

    March 31,
     
     2021  2020 
    Collaboration revenue$4,789  $750 
    Operating expenses:       
    Research and development 16,334   14,482 
    General and administrative 5,498   5,064 
    Total operating expenses 21,832   19,546 
    Loss from operations (17,043)  (18,796)
    Other income, net 44   344 
    Net loss$(16,999) $(18,452)
    Net loss per share, basic and diluted$(0.54) $(0.81)
    Weighted-average common shares outstanding, basic and diluted 31,510   22,719 



    Contact:

    Investors:

    Christi Waarich

    Director, Investor Relations and

    Corporate Communications



    617-651-8664

    Stephanie Ascher

    Stern Investor Relations, Inc.



    212-362-1200

    Media:

    Kaitlin Gallagher

    Berry & Company Public Relations



    212-253-8881



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