ARMGO Pharma, Inc.

ARMGO Pharma Publishes Positive Phase 1b Trial Results of Rycal® ARM210 for the Treatment of Ryanodine Receptor 1 Related Myopathies Phase 1b open label trial confirms safety and tolerability of 120 mg and 200 mg dosing of ARM210 daily in patients with Ryanodine Receptor 1 Related Myopathies Provides first signs of clinical efficacy improving fatigue and proximal muscle strength in patients at 200 mg daily Corroborates allosteric mechanism of action of Rycal® ARM210 to restore muscle function by repairing mutated ‘leaky’ Ryanodine Receptor 1 channels January 29, 2024 – ARMGO Pharma, Inc. (ARMGO), a clinical stage biopharmaceutical company advancing a novel class of small molecule drugs known as Rycals®, announced today the publication of the results from a Phase 1b study of its Rycal ARM210 (also known as S48168), for the treatment of Ryanodine Receptor 1 Related Myopathies (RYR1-RM), an orphan muscle disease. The data was published in a paper entitled ‘Rycal S48168 (ARM210) for RYR1-related myopathies: A phase one, open-label, dose-escalation trial’ authored by Dr Joshua Todd et al in the peer reviewed Journal eClinicalMedicine, part of the Lancet family of publications. The paper reviews data from the Phase 1b study of ARM210 and its novel allosteric mechanism of action (MoA) targeting the root cause of RYR1-RM: mutated Ryanodine Receptor 1 (RYR1). The RYR1 gene encodes RyR1, an intracellular calcium-release channel that becomes leaky in muscle diseases. Intracellular calcium leaks caused by mutant RyR1 channels impair muscle contraction leading to muscle weakness and loss of function, and activate toxic pathways that damage muscle, causing the symptoms in RYR1-RM. The Phase 1b, open-label, dose-escalation trial confirmed safety, tolerability and pharmacokinetics of 120 and 200 mg dosing of ARM210 daily over for 29 days in adult men and women affected with RYR1-RM. Importantly, it also demonstrated preliminary efficacy in the higher dose group in two hallmark symptoms of RYR1-RM: 1) significant alleviation of fatigue assessed by PROMIS-fatigue t-scores and 2) improved proximal muscle strength assessed by physical shoulder abduction exam (Medical Research Council grading). These results warrant further development of ARM210 as a potential disease modifying treatment for RYR1-RM in a randomized, placebo-controlled Phase 2 trial. The completed Phase 1b trial was conducted in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) under a Cooperative Research and Development Agreement (CRADA), with the support of the RYR-1 Foundation, Pittsburgh, PA, USA. “We are very pleased with the results of the RYR1-RM trial conducted together with the NIH, as the study has confirmed the safety and tolerability of ARM210, but most importantly, it has demonstrated for the first time that our Rycal®, ARM210, can reverse symptoms of this devastating, chronic muscle disease in a short treatment period. That is very promising”, said Gene Marcantonio, M.D., Ph.D., Chief Executive Officer of ARMGO Pharma. “We look forward, therefore, to rapidly continuing the development of ARM210 to bring this potential first treatment to RYR1-RM patients with the support of the RYR-1 Foundation and the patient community.” Michael F. Goldberg, M.D., M.P.H., Co-Chair of Research of the RYR-1 Foundation added, “We are elated by the publication of this important study, as it represents a beacon of hope for the many individuals and families from around the world who are affected by RYR1-RM. We look forward to the next stages in the development of this important drug.” Further information about this Phase 1b trial can be found online at: https://clinicaltrials.gov/study/NCT04141670. The trial was supported by Intramural Research Programs of the NIH/NINDS, NIH/NINR, a NIH Clinical Center Bench to Bedside Award (2017-551673) and ARMGO’s previous collaboration partner Les Laboratoires Servier. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publication reference: Rycal S48168 (ARM210) for RYR1-related myopathies: a phase one, open-label, dose-escalation trial, Todd et al, eClinicalMedicine https://www-thelancet-com.libproxy1.nus.edu.sg/journals/eclinm/article/PIIS2589-5370(24)00012-9/fulltext ARM210 (S48168) is a small molecule of the Rycal class, owned and developed by ARMGO for the treatment of Ryanodine Receptor mediated diseases such as RYR1-RM. It is an allosteric modulator that binds preferentially to leaky RyR channels and repairs the leak, as previously demonstrated in vitro in muscle biopsies from RYR1-RM patients. ARM210 (S48168) is currently undergoing Phase 2 clinical development for a second orphan indication, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a genetic arrhythmia caused by mutations in RYR2, the cardiac calcium channel gene. ARM210 (S48168) was awarded orphan drug designation for RYR1-RM in 2018 by the FDA and for CPVT in 2020. ARMGO also has a rare pediatric disease designation for CPVT. ARMGO Pharma, Inc., is a privately held biopharmaceutical company dedicated to developing novel small-molecule therapeutics to treat cardiac, and musculoskeletal disorders characterized by leaky Ryanodine Receptor (RyR) calcium channels. The Company’s proprietary drugs, known as Rycals®, are a new class of oral agents that repair these leaky calcium channels. ARM210, ARMGO’s most advanced Rycal, is currently in clinical development for two rare and orphan diseases, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a life-threatening cardiac disease and RYR1-Related Myopathy (RYR1-RM) a severe muscle disease. ARMGO Pharma has an exclusive, worldwide license from Columbia University for its RyR technology based on the research of founding scientist Andrew R. Marks, M.D. The Pittsburgh, Pennsylvania-based 501(c)(3) public charity was launched in October 2014. It is currently the only organization that exists solely to advocate for and serve the needs of individuals affected by RYR-1-related diseases (RYR-1-RD), the most common cause of congenital myopathy. The RYR-1 Foundation supports research leading to an effective treatment or a cure for RYR-1-RD. To achieve this mission, The RYR-1 Foundation has several goals: 1) Support Research: The RYR-1 Foundation makes grants to researchers interested in RYR-1-RD. Developing a patient registry is also key to promoting clinical trials of potential therapies. 2) Medical Professional Education: The vast majority of medical professionals have never heard of RYR-1-RD. The RYR-1 Foundation raises awareness through resources on our website, including the latest medical literature, as well as direct meetings with medical professionals around the world. 3) Patient/Family Support and Advocacy: Due to the rarity of RYR-1-RD, receiving this diagnosis can be an anxiety-provoking and isolating experience for an affected patient and their families. The RYR-1 Foundation serves as a resource for patients and their families through our website, other forms of social media, and family conferences. The content above comes from the network. if any infringement, please contact us to modify.

Planned Leadership Transition to Accelerate the Company’s Next Stage of Growth; Founding CEO Ashish Nimgaonkar, M.D., Transitions to Chief Medical Officer and Head of R&D Lead Candidate, GLY-200, Ready to Begin Phase 2b Development for Obesity and Type 2 Diabetes BOSTON--(BUSINESS WIRE)-- Glyscend Therapeutics, a clinical-stage biopharmaceutical company that is reshaping the treatment of metabolic disease, including obesity and type 2 diabetes, with first-in-class oral polymer medicines that address unmet needs for patients globally, today announced the appointment of Sapan Shah, Ph.D., as Chief Executive Officer. Dr. Shah has more than 25 years of experience leading innovative life science companies as CEO, founder, board member and strategic advisor. His appointment is part of a planned leadership transition to accelerate Glyscend’s growth as it further advances lead product candidate, GLY-200, a clinical stage oral polymer medicine targeting gut mediated metabolic signaling. In conjunction with the transition, founding CEO, Ashish Nimgaonkar, M.D., was appointed to the newly created role of Chief Medical Officer and Head of Research and Development. “I am thrilled to welcome Sapan to the team and excited to partner with him through the next phase of Glyscend’s growth. I also want to commend the entire Glyscend team for their dedication and efforts in getting the company to its current stage,” stated Dr. Nimgaonkar. “GLY-200 is well-positioned to advance into a Phase 2b trial for patients with obesity and type 2 diabetes, and I look forward to collaborating with Sapan to progress our lead program and bring forward additional therapies for patients living with metabolic diseases.” “Under Ashish’s leadership, Glyscend has made tremendous progress going from scientific hypothesis to clinical proof-of-concept in a positive Phase 2a trial. His insights across our clinical and research portfolio will be crucial to our continued success,” said Dennis McWilliams, Partner at Santé Ventures and Chair of Glyscend’s Board of Directors. “We are delighted to bring in Sapan at this pivotal time, with his deep experience in executing financings, business development deals and operational buildouts for development-stage companies. Together with our existing leadership, we have a clear path toward execution of our near- and long-term goals.” Dr. Shah has significant leadership experience in the biopharma industry, with a focus on building, financing and operating innovative companies advancing novel therapeutics that address critical areas of unmet medical need. His previous CEO roles have included StrideBio, a leading developer of novel adeno-associated virus (AAV) based gene therapies with a pioneering structure-driven capsid engineering platform that was acquired by Gingko Bioworks in 2023; ARMGO Pharma, a clinical-stage company advancing treatments for debilitating cardiac and rare muscle diseases; Ezose Sciences, a high-throughput glycomics platform company acquired by Sumitomo Bakelite in 2014; and Shionogi Inc., the U.S. pharmaceutical business of Shionogi & Co, Ltd. At StrideBio, Dr. Shah led efforts to expand the company’s capabilities and pipeline, execute multiple pharmaceutical partnerships and close a Series B financing with a top venture syndicate. At Shionogi, Dr. Shah launched the company’s initial U.S. business, ultimately building a fully integrated clinical development and commercial organization, including overseeing development programs and marketed products in the obesity and diabetes area. Dr. Shah began his career as a consultant with McKinsey & Company, where he advised pharmaceutical and biotech clients on a wide range of R&D, commercial and corporate strategy initiatives. Dr. Shah holds a Ph.D. in Molecular Biophysics and Biochemistry from Yale University and B.A. degrees in Mathematics, Biochemistry and Integrated Science from Northwestern University. “I am grateful for the opportunity to build on the fantastic progress made by Ashish and the entire Glyscend team, and to lead the next phase of growth. This is a transformative time for obesity and type 2 diabetes patients with current therapies showing remarkable results. However, significant unmet needs persist with large numbers of patients remaining uncontrolled or unable to tolerate available treatments. Given the magnitude of the global obesity-diabetes epidemic, new oral therapies with mechanisms of action that are complementary to existing approaches are urgently needed,” said Dr. Shah. “Based on recent Phase 2a clinical results, GLY-200 has the potential to offer obesity and type 2 diabetes patients an oral, well-tolerated and effective therapy. I look forward to working alongside the Glyscend team and Board to bring this important medicine to patients.” About Glyscend, Inc. Glyscend Therapeutics is a clinical-stage biopharmaceutical company that is reshaping the treatment of metabolic disease, led by obesity and type 2 diabetes (T2D), with first-in-class oral polymer medicines with the potential to address significant unmet needs for patients globally. The company’s lead candidate, GLY-200, is designed to be non-absorbed and selectively target and bind to the inner lining of the upper GI tract, where it can modulate nutrient sensing and downstream metabolic signaling pathways. Based on its unique mechanism of action, GLY-200 mimics the beneficial effects of metabolic surgery and duodenal exclusion devices. In a Phase 2a study in patients with T2D, GLY-200 was well-tolerated and demonstrated clinical proof-of-concept, with statistically significant improvements on glycemic control and body weight as well as potential beneficial effects on other metabolic markers. Glyscend plans to advance GLY-200 into longer term Phase 2b studies in patients with obesity and T2D. The company is backed by healthcare innovators, Santé Ventures and Brandon Capital Partners, and was founded based on research and funding from Johns Hopkins University, the Thiel Foundation and Breakout Labs. For more information, please visit .

Trial to investigate the safety and efficacy of ARM210 for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Lead molecule ARM210 repairs ‘leaky’ Ryanodine Receptor (RyR) channels to restore intracellular calcium signaling in cardiac and musculoskeletal disorders ARDSLEY, N.Y.--(BUSINESS WIRE)-- ARMGO Pharma, Inc. (ARMGO), a clinical stage biopharmaceutical company advancing a novel class of small molecule drugs known as Rycals®, announced today the enrollment of the first patient in a Phase 2 proof of concept clinical trial using its Rycal ARM210 (also known as S48168), for the treatment of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The trial, performed at the Amsterdam University Medical Center (Amsterdam UMC), Netherlands and the Mayo Clinic, Rochester MN, USA will investigate the safety and efficacy of ARM210 in CPVT. CPVT is a rare genetic heart disease causing arrhythmia. It affects 1:10,000 people with a fatality rate of 30-50% by the age of 40 if left untreated. CPVT is caused by dysregulation of intracellular calcium handling in cardiomyocytes resulting mainly from mutations in Ryanodine Receptor 2 (RyR2), an intracellular calcium-release channel. Such mutations render RyR2 channels leaky, leading to inappropriate channel opening during periods of exercise or stress, resulting in severe and often fatal arrhythmias. ARM210 is a potential disease modifying therapy for CPVT as it repairs leaky RyR2 channels. By binding and stabilizing the leaky channel, ARM210 can restore normal function, as demonstrated in animal models and in high resolution structures of mutant RyR2. In addition to CPVT, this unique mechanism of ARM210 has potential use in other RyR-mediated cardiac and skeletal muscle diseases, such as the genetic muscle disorder Ryanodine Receptor 1-Related Myopathy (RYR1-RM). "This trial represents an important milestone for ARMGO and the CPVT community, potentially providing a disease modifying treatment for CPVT and validating ARM210’s unique mechanism of action for Ryanodine Receptors" stated Gene Marcantonio, M.D. Ph.D., Chief Executive Officer of ARMGO Pharma. “We are looking forward to advancing this important clinical program in partnership with the leading CPVT experts Arthur Wilde, M.D., Ph.D. and Michael Ackerman, M.D., Ph.D. and we are confident in the success of this trial. In addition, we are building our portfolio to strengthen ARMGO’s position as a pioneer of Rycal-based treatments for Ryanodine Receptor-related disorders.” ARMGO was granted orphan drug designation as well as rare pediatric disease designation by the FDA in 2020 for the use of ARM210 as a potential treatment for patients with CPVT. The phase 2 trial is supported in part by an Orphan Products Development (OPD) grant from the FDA (1R01FD007279). Further information about the trial can be found at with identifier - NCT05122975. ENDS View source version on businesswire.com: Contacts Sarah Jeffery Tel: +44 (0)7771 730919 E-mail: sarah.jeffery@zymecommunications.com Source: ARMGO Pharma, Inc. View this news release online at: