Ninerafaxstat

PDUFA Date for Aficamten in Obstructive HCM Extended by FDA to December 26, 2025 Topline Results from MAPLE-HCM Expected in May Enrollment Completed in ACACIA-HCM; Topline Results Expected in 1H 2026 ~$1.1 Billion in Cash, Cash Equivalents and Investments as of March 31, 2025 SOUTH SAN FRANCISCO, Calif. , May 06, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) reported a management update and financial results for the first quarter of 2025. “In the first quarter, we made progress towards commercial readiness and advanced our specialty cardiology pipeline,” said Robert I. Blum , Cytokinetics’ President and Chief Executive Officer. “Recently, our PDUFA date for aficamten in obstructive HCM was extended by FDA to provide time to review a REMS submission made at the Agency’s request subsequent to the initial NDA filing acceptance. We remain confident in the distinct benefit-risk and pharmaceutic profile of aficamten, and our top priority is bringing this potential therapy to patients. This month, we also expect to report topline results from MAPLE-HCM, and we continue conduct of ACACIA-HCM, for which we have now completed enrollment of patients. With a strong balance sheet and prudent attention to capital deployment, we are well positioned to deliver across regulatory, clinical and commercial milestones.” Q1 and Recent Highlights Cardiac Muscle Programs aficamten (cardiac myosin inhibitor) The U.S. Food & Drug Administration (FDA) extended the Prescription Drug User Fee Act (PDUFA) target action date for the New Drug Application (NDA) for aficamten for the treatment of patients with obstructive hypertrophic cardiomyopathy (HCM) to December 26, 2025 . Following pre-NDA discussions with FDA in which safety and risk mitigation were discussed, Cytokinetics submitted the NDA for aficamten in obstructive HCM without an accompanying REMS and the FDA accepted the NDA for filing. During the NDA review, the FDA requested that Cytokinetics submit a REMS consistent with the inherent characteristics of aficamten, which the company provided. The submission of a REMS has now been determined by FDA to be a Major Amendment to the NDA resulting in a standard three-month extension to the original PDUFA action date. No additional clinical data or studies have been requested of Cytokinetics by FDA. Completed a mid-cycle review meeting with FDA for the NDA for aficamten. The FDA indicated that it does not plan to convene an Advisory Committee meeting to review the NDA for aficamten. We expect to participate in a late-cycle meeting with the FDA in June. Received Day 120 List of Questions from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) regarding the Marketing Authorization Application (MAA) for aficamten for the treatment of obstructive HCM and have begun to prepare responses. Continued to support the review of the NDA for aficamten for obstructive HCM by the Center for Drug Evaluation (CDE) in China . Advanced the ongoing clinical trials program for aficamten: Continued conduct of MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial comparing aficamten as monotherapy to metoprolol as monotherapy in patients with symptomatic obstructive HCM. We expect to share topline results in May 2025 . Completed enrollment in the primary cohort (excluding Japan ) of ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), a pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, in Q1 2025, ahead of schedule and with over 500 patients enrolled, surpassing the original enrollment target. We expect to share topline results in 1H 2026. Updated the primary endpoint for ACACIA-HCM from a single primary endpoint of change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score to a dual primary endpoint of change in KCCQ Clinical Summary Score and change in maximal exercise performance (peak VO2) from baseline to Week 36. This change in the primary endpoint is intended to unify the protocol and statistical analysis plans across regions in response to feedback from global regulators. The update to the primary endpoint does not change conduct of the clinical trial. Conducted start-up activities for the Japan cohort of ACACIA-HCM with enrollment expected to begin in Q2 2025 to support regulatory activities in Japan . Continued enrolling patients in CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM), a clinical trial of aficamten in a pediatric population with symptomatic obstructive HCM. We expect to complete patient enrollment of the adolescent cohort in 2H 2025. Completed conduct of the Phase 1 study of aficamten in healthy Japanese and Caucasian participants. Continued conduct of MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial comparing aficamten as monotherapy to metoprolol as monotherapy in patients with symptomatic obstructive HCM. We expect to share topline results in May 2025 . Completed enrollment in the primary cohort (excluding Japan ) of ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), a pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, in Q1 2025, ahead of schedule and with over 500 patients enrolled, surpassing the original enrollment target. We expect to share topline results in 1H 2026. Updated the primary endpoint for ACACIA-HCM from a single primary endpoint of change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score to a dual primary endpoint of change in KCCQ Clinical Summary Score and change in maximal exercise performance (peak VO2) from baseline to Week 36. This change in the primary endpoint is intended to unify the protocol and statistical analysis plans across regions in response to feedback from global regulators. The update to the primary endpoint does not change conduct of the clinical trial. Conducted start-up activities for the Japan cohort of ACACIA-HCM with enrollment expected to begin in Q2 2025 to support regulatory activities in Japan . Continued enrolling patients in CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM), a clinical trial of aficamten in a pediatric population with symptomatic obstructive HCM. We expect to complete patient enrollment of the adolescent cohort in 2H 2025. Completed conduct of the Phase 1 study of aficamten in healthy Japanese and Caucasian participants. Presented new analyses at the American College of Cardiology Annual Scientific Session and Expo related to aficamten expanding on its metabolic pathways, combination therapy with disopyramide and longer-term effects on cardiac structure and function. Expanded U.S. commercial readiness activities for aficamten including initiating sales force recruiting. Continued building our bespoke patient support programs by contracting with strategic partners and finalizing the design of our customer-facing teams. Confirmed channel distribution partners and continued market research on our promotional launch campaign. Advanced European commercial readiness activities including hiring key leadership positions in Europe , establishing new regional entities in France and the U.K. , validating our reimbursement strategy and began developing our Health Technology Assessment (HTA) dossiers. Published the following manuscripts: “Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy” in the Journal of the American College of Cardiology : Heart Failure “Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM Rationale, Study Design, and Baseline Characteristics” in the Journal of the American College of Cardiology : Heart Failure “Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten” in Clinical Pharmacokinetics “Clinical Evaluation of the Effect of Aficamten on QT/QTc Interval in Healthy Participants” in Clinical and Translational Science “A Characterization of the Nonclinical Pharmacology and Toxicology of Aficamten, a Reversible Allosteric Inhibitor of Cardiac Myosin” in the International Journal of Toxicology “Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy” in the Journal of the American College of Cardiology : Heart Failure “Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM Rationale, Study Design, and Baseline Characteristics” in the Journal of the American College of Cardiology : Heart Failure “Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten” in Clinical Pharmacokinetics “Clinical Evaluation of the Effect of Aficamten on QT/QTc Interval in Healthy Participants” in Clinical and Translational Science “A Characterization of the Nonclinical Pharmacology and Toxicology of Aficamten, a Reversible Allosteric Inhibitor of Cardiac Myosin” in the International Journal of Toxicology omecamtiv mecarbil (cardiac myosin activator) Continued conduct of COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction. We expect to continue enrollment through 2025 to enable completion of enrollment in 2026. CK-4021586 (CK-586, cardiac myosin inhibitor) Continued conduct of AMBER-HFpEF (Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF), a Phase 2 clinical trial of CK-586 in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) with left ventricular ejection fraction (LVEF) ≥ 60%. We expect to complete patient enrollment of the first two cohorts in 2H 2025. CK-4015089 (CK-089, fast skeletal muscle troponin activator) Conducted the initial single ascending dose cohorts of the Phase 1 randomized, double-blind, placebo-controlled clinical study of CK-4015089 (CK-089) in healthy human participants. Pre-Clinical Development and Ongoing Research Continued pre-clinical development and research activities directed to additional muscle biology focused programs. Corporate Participated in Series B financing of Imbria Pharmaceuticals to support advancement of ninerafaxstat for the treatment of non-obstructive HCM. Released the 2024 Corporate Responsibility Report outlining the Company’s commitment and activities related to social and environmental responsibility, ethics and governance and patient and community engagement. Launched EARTH-HCM (Epidemiology, Awareness, Real-world Treatment and Health Outcomes in HCM), an online, open access, interactive public health education tool developed by Cytokinetics in collaboration with leading academic institutions, that leverages real-world, de-identified claims data to visualize and analyze population differences in patient characteristics, treatments, clinical outcomes, healthcare resource utilization and costs in HCM in the U.S. Awarded Cytokinetics Communications Fellowship Grants to patient advocacy organizations serving the HCM and heart failure communities to support increased capacity in communications, awareness building and community engagement. First Quarter 2025 Financial Results Cash, Cash Equivalents and Investments As of March 31, 2025 , the company had approximately $1.1 billion in cash, cash equivalents and investments compared to $1.2 billion at December 31, 2024 . Cash, cash equivalents and investments declined by approximately $132.2 million during the first quarter of 2025. Revenue Total revenues for the first quarter of 2025 were $1.6 million compared to $0.8 million for the same period in 2024. Research and Development (R&D) Expenses R&D expenses for the first quarter of 2025 were $99.8 million , which included $11.7 million of non-cash stock-based compensation expense, compared to $81.6 million for the same period in 2024, which included $8.6 million of non-cash stock-based compensation expense. The increase was primarily due to advancing our clinical trials and higher personnel-related costs. General and Administrative (G&A) Expenses G&A expenses for the first quarter of 2025 were $57.4 million , which included $11.9 million of non-cash stock-based compensation expense, compared to $45.5 million for the same period in 2024, which included $13.0 million of non-cash stock-based compensation expense. The increase was primarily due to investments in commercial readiness and higher personnel-related costs. Net Income (Loss) Net loss for the first quarter of 2025 was $161.4 million , or $(1.36) per share, basic and diluted, compared to a net loss of $135.6 million , or $(1.33) per share, basic and diluted, for the same period in 2024. 2025 Financial Guidance The company is maintaining its full year 2025 financial guidance: *GAAP operating expense comprised of R&D and SG&A expenses. Anticipated year-over-year increase in GAAP operating expense includes investments toward commercial readiness for the potential approval and launch of aficamten for patients with obstructive HCM. The financial guidance does not include the effect of GAAP adjustments as may be caused by events that occur subsequent to publication of this guidance, including but not limited to Business Development activities. Conference Call and Webcast Information Members of Cytokinetics’ senior management team will review the company’s first quarter 2025 results on a conference call today at 4:30 PM Eastern Time . The conference call will be simultaneously webcast and can be accessed from the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Cytokinetics Q1 2025 Earnings Conference Call. Upon registration, participants will receive a dial-in number and a unique passcode to access the call. An archived replay of the webcast will be available via Cytokinetics’ website for twelve months. About Cytokinetics Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology to advance a pipeline of potential new medicines for patients suffering from diseases of cardiac muscle dysfunction. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a cardiac myosin inhibitor following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten, for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function. For additional information about Cytokinetics , visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but not limited to, statements, express or implied, relating to our or our partners’ research and development and commercial readiness activities, including the initiation, conduct, design, enrollment, progress, continuation, completion, timing and results of any of our clinical trials, or more specifically, our receipt of regulatory approval by FDA or any other regulatory authority to enable our commercialization of aficamten in the United States or any other jurisdiction by the target PDUFA date or any other date, if ever, our ability to complete enrollment of CEDAR-HCM and AMBER-HFpEF in the second half of 2025, our ability to complete patient enrollment of COMET-HF in 2026, our ability to commence enrollment of ACACIA-HCM in Japan in the second quarter of 2025, our ability to announce the results of any of our clinical trials by any particular date, the timing of interactions with FDA or any other regulatory authorities in connection to any of our drug candidates and the outcomes of such interactions; statements relating to the potential patient population who could benefit from aficamten, omecamtiv mecarbil, CK-586, CK-089 or any of our other drug candidates; statements relating to our ability to receive additional capital or other funding, including, but not limited to, our ability to meet any of the conditions relating to or to otherwise secure additional loan disbursements under any of our agreements with entities affiliated with Royalty Pharma or additional milestone payments from Sanofi or Bayer in connection with our collaborations for aficamten in China or Japan respectively; statements relating to our operating expenses or cash utilization for the remainder of 2025 or any other period, statements relating to our cash balance at any particular date or the amount of cash runway such cash balances represent at any particular time and statements related to the potential benefits of our participation in the Series B financing of Imbria Pharmaceuticals to support the advancement of ninerafaxstat for the treatment of nHCM. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to Cytokinetics’ need for additional funding and such additional funding may not be available on acceptable terms, if at all; potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval; patient enrollment for or conduct of clinical trials may be difficult or delayed; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ or its partners’ ability to conduct clinical trials; Cytokinetics may incur unanticipated research and development and other costs; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission , particularly under the caption “Risk Factors” in Cytokinetics’ Annual Report on Form 10-K for the year ended December 31, 2024 . Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact: Cytokinetics Diane Weiser Senior Vice President, Corporate Affairs(415) 290-7757 Source: Cytokinetics, Incorporated

A biotech incubated by RA Capital has secured a $57.5 million Series B to begin a mid-stage trial for its cardio drug this quarter and get to a readout in late 2026. Imbria Pharmaceuticals has now raised a total of about $150 million in equity financing, CEO Alvin Shih exclusively told Endpoints News . The Boston startup, which has eight employees, has not previously disclosed its fundraising. Imbria’s financial backers include RA, SV Health Investors, Deep Track Capital, AN Ventures and Catalio Capital Management. The money is expected to help the company prove whether its oral medicine, code-named ninerafaxstat , can treat patients with non-obstructive hypertrophic cardiomyopathy, or HCM, in a Phase 2b study. The biotech now has a runway into the second half of 2027, according to Shih, who joined Imbria as a board member last year and is now CEO. Anne Prener, a former partner at SV Health, was president and CEO of Imbria from 2020 until September, according to her LinkedIn. Shih has spent the past few quarters trying to secure funding in a challenging market. “It has not been easy. The environment is very difficult, but I would say raising money for my previous company — Catamaran [Bio] in the cell therapy space — was impossible,” he said, referring to the CAR-NK cell therapy biotech that closed last year . “This was just difficult.” Imbria will also benefit from the expertise of Cytokinetics, which chipped into the startup’s Series B. “Their involvement validates our approach,” Shih said. The California drug developer’s aficamten is in late-stage development in similar cardio fields as Imbria’s ninerafaxstat; however, Cytokinetics doesn’t have any operational control over ninerafaxstat, Shih confirmed. Eventually, and maybe with the help of a partner, Imbria plans to continue testing the twice-daily drug in other cardio indications like heart failure with preserved ejection fraction, or HFpEF. The drug has already gone through a Phase 2a in HFpEF. Imbria said the drug met the trial’s primary endpoint in a presentation at last month’s annual American College of Cardiology conference. “It’s become an epidemic,” Shih said. “HFpEF is the fastest-growing segment of heart failure, and it’s clear that even with GLP-1s, you haven’t totally fixed the problem, and so patients are going to need additional therapeutics.” Ninerafaxstat is a partial fatty acid oxidation (pFOX) inhibitor. Shih said the goal is to make the heart less reliant on fatty acids, which is common in heart failure patients, and more reliant on glucose, which could boost metabolism and make for a more well-oiled mitochondrial engine. With better energy generation, cardiac function should improve. Shih said the experimental oral drug has demonstrated improvement in “cardiac energetics,” key functional outcomes and quality of life outcomes, including on the Kansas City Cardiomyopathy Questionnaire, a self-administered survey for heart failure patients. “That is what is going to be the approvable endpoint in both HCM and HFpEF,” Shih said. RA Capital got the idea from a decades-old drug called trimetazidine , which has been commercialized in Europe to treat angina but is not approved by the FDA. “It’s known to have some activity in the cardiac mitochondria, but what they wanted to do was to optimize the molecule and they ended up creating a new molecule that results in trimetazidine as one of its metabolites, but also has other active metabolites,” Shih said. It’s “sort of getting more bang for the buck on the mechanism, which is in the mitochondria.”