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Industry veteran with late-stage clinical development, medical affairs, and regulatory experience; well-positioned to advance losmapimod towards a potential regulatory submission and approval Interim Chief Medical Officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as senior vice president (SVP) of early development CAMBRIDGE, Mass., March 18, 2024 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.® (Fulcrum) (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced the appointment of Patrick Horn, M.D., Ph.D., as chief medical officer, effective immediately. Dr. Horn is a seasoned executive with over 20 years of end-to-end drug development experience spanning multiple therapeutic areas, with an emphasis on rare diseases, across both large pharmaceutical and biotech companies. Interim chief medical officer, Iain Fraser, MBChB, DPhil, will continue to serve on Fulcrum’s executive leadership team as SVP of early development. Together, Drs. Horn and Fraser will be responsible for leading clinical development and overseeing regulatory strategy and execution. “I am very pleased to enrich our leadership team with Pat, an accomplished industry veteran who has successfully guided multiple therapies—including rare disease programs lacking existing regulatory pathways—through late clinical development, regulatory approval, and commercial launch,” said Alex C. Sapir, Fulcrum’s president and chief executive officer. “This is a key moment for Fulcrum as we continue to advance our Phase 3 REACH trial of losmapimod for patients with facioscapulohumeral muscular dystrophy and reinitiate our Phase 1b PIONEER trial of pociredir in sickle cell disease. We believe both Pat and Iain’s complementary expertise will be invaluable as we near several pivotal milestones for our two key clinical programs and advance our early-stage pipeline.” Dr. Horn added, "Joining Fulcrum is an exciting opportunity to bring potentially transformative therapies to patients especially as we advance towards near-term inflection points for losmapimod, a late-stage clinical program with first-to-market potential, and pociredir, a highly differentiated oral treatment option that may shift the current standard of care. Building on the encouraging clinical data generated to date, I, alongside Iain, look forward to working with the management team to deliver on the promise of Fulcrum’s differentiated pipeline of rare disease programs.” Dr. Patrick Horn is a distinguished professional with over 20 years of experience in the field of rare disease drug development, encompassing all stages from initial research to regulatory approval and commercial launch. His most recent role was as the Chief Medical Officer at HemoShear Therapeutics, specializing in rare metabolic diseases. Previously, he held the position of Chief Medical Officer at Albireo Pharma where he led the team that achieved marketing approvals in the US and Europe for Bylvay™ in progressive familial intrahepatic cholestasis (PFIC). Before his tenure at Albireo, he served as the Senior Vice President of Medical and Clinical Development at Orphan Technologies, directing the advancement of novel treatments for homocystinuria. Prior to this, he was the Chief Medical Officer at Tetraphase Pharmaceuticals, where he oversaw the clinical development of antibiotic candidates, including the program leading to the New Drug Application for eravacycline. Before Tetraphase, Dr. Horn led the clinical program at Dyax Corp. that resulted in the approval of Kalbitor® for the treatment of hereditary angioedema. Dr. Horn received his M.D., and Ph.D., from the University of Chicago and completed his pediatric residency at Boston Children’s Hospital. Prior to transitioning to industry, Dr. Horn was a practicing pediatrician at major academic institutions in Chicago. About Fulcrum Therapeutics Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum’s two lead programs in clinical development are losmapimod, a small molecule in development for the treatment of facioscapulohumeral muscular dystrophy (FSHD), and pociredir (formerly known as FTX-6058), a small molecule designed to increase expression of fetal hemoglobin and in development for the treatment of sickle cell disease (SCD). Fulcrum uses proprietary technology to identify drug targets that can modulate gene expression to treat the known root cause of gene mis-expression. For more information, visit and follow us on Twitter/X (@FulcrumTx) and LinkedIn. 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. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including express or implied statements regarding advancement of losmapimod towards regulatory submission and approval;; reinitiation of the Phase 1b trial; advancement of Fulcrum’s early-stage pipeline; Fulcrum’s ability to deliver an FDA-approved therapy for FSHD patients; and the potential for pociredir to shift the standard of care;; among others. 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 continue to advance its product candidates in clinical trials; initiating and enrolling clinical trials on the timeline expected or at all; obtaining and maintaining necessary approvals from the FDA and other regulatory authorities; replicating in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, pociredir and any other product candidates; obtaining, maintaining or protecting intellectual property rights related to its product candidates; managing expenses; managing executive and employee turnover, including integrating a new CMO; and raising the substantial additional capital needed to achieve its business objectives, among others. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum’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 Fulcrum’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum’s views as of the date hereof and should not be relied upon as representing Fulcrum’s views as of any date subsequent to the date hereof. Fulcrum anticipates that subsequent events and developments will cause Fulcrum’s views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so. Contact: Chris Calabrese LifeSci Advisors, LLC ccalabrese@lifesciadvisors.com 917-680-5608

An Ionis Pharmaceuticals drug has preliminary data showing it met the main goal of its pivotal test in a rare disease with only a handful of approved treatments. With these results in hand, Ionis is now preparing to submit its drug candidate for FDA review. However, the key data that will determine how competitive the drug could be won’t become available until later this year. The Ionis drug, donidalorsen, is in development for hereditary angioedema (HAE), an inherited disease that leads to swelling attacks throughout the body. When these attacks close off the airway, they can become life threatening. Ionis reported Monday that its subcutaneously injected drug met the main trial goal of reducing the rate of angioedema attacks dosed every four weeks or every eight weeks compared to a placebo. The drug was well tolerated by patients and no serious adverse events were reported in the treatment group, according to the Carlsbad, California-based company. Ionis did not provide additional details about donidalorsen’s safety or the reduction in HAE attacks, but said it plans to present the Phase 3 results at an upcoming medical meeting this year. In Phase 2 testing, the average reduction in HAE attacks compared to a placebo was 90% in weeks one to 17. Furthermore, Phase 2 results showed 92% of treated patients were attack free versus 0% in the placebo arm from weeks five to 17. “We are very pleased with the positive topline results from the Phase 3 OASIS-HAE study of donidalorsen,” Kenneth Newman, senior vice president, head of clinical development at Ionis, said in a prepared statement. “Based on these results and the durable efficacy and favorable safety data seen in the ongoing Phase 2 open-label extension study, we believe donidalorsen, if approved, could be an attractive new treatment option for patients with HAE, many of whom continue to experience unpredictable, painful and severe breakthrough attacks despite currently available prophylactic treatments.” Ionis’s drugs are based on antisense oligonucleotides, small pieces of DNA or RNA that bind to messenger RNA to stop the production of a disease-causing protein. Donidalorsen is designed to target the mRNA responsible for producing a protein called prekallikrein, a precursor to the kallikrein protein that contributes to HAE attacks. If Ionis can bring its HAE drug to the market, it would compete against Takeda Pharmaceutical’s Kalbitor, an injectable kallikrein inhibitor. Another Takeda HAE drug, Firazyr, blocks a different protein called bradykinin. BioCryst Pharmaceuticals has commercialized an oral kallikrein inhibitor branded as Orladeyo. KalVista Pharmaceuticals has reached Phase 3 testing with sebetralstat, an oral kallikrein inhibitor developed as an on-demand treatment for HAE attacks. KalVista expects to report preliminary Phase 3 data early this year. Ionis said the scientific meeting presentation of donidalorsen’s Phase 3 data will happen by mid-2024. That’s also the time frame for reporting results from the open-label extension of the Phase 3 test and the separate group of patients who have transitioned to the Ionis drug from another prophylactic. These are the key data that will determine how the Ionis drug could match up against the competition. In a note sent to investors Monday, Leerink Partners analyst Mani Foroohar wrote that these results will clarify whether donidalorsen’s commercial profile supports broad switching from other drugs or if it will be driven mainly by newly diagnosed patients. Ionis plans to handle U.S. commercialization of donidalorsen if it’s approved. European commercialization is in the hands of Otsuka Pharmaceutical. In December, Ionis struck a deal granting Otsuka those rights in exchange for a $65 million upfront payment. The deal makes Otuska responsible for European regulatory submissions. The Japanese drugmaker would owe Ionis milestone payments and royalties from its sales of the drug in Europe. Image by Getty Images