Author: Daniel Cojocaru

• 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

ARDSLEY, N.Y., 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/journals/eclinm/article/PIIS2589-5370(24)00012-9/fulltext

 

Contacts

ARMGO Pharma Inc

E-mail: info@armgo.com

ICR Consilium

Ashley Tapp / Lindsey Neville/ Renna Foufouni

E-mail: armgo@consilium-comms.com

Tel: +44 (0)20 3709 5700

 

About ARM210

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.

 

About ARMGO Pharma

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.

For more information, please visit http://www.armgo.com

 

About RYR-1 Foundation

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.

For more information, please visit http://www.ryr1.org

• 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., June 21, 2023 – 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 https://clinicaltrials.gov/ with identifier – NCT05122975.

 

About ARMGO Pharma

ARMGO Pharma, Inc., is a privately held biopharmaceutical company dedicated to applying targeted mechanism-based science to the development of novel small-molecule therapeutics to treat cardiac, and musculoskeletal disorders characterized by leaky Ryanodine Receptor (RyR) calcium channels. Leaky RyRs are caused by genetic mutations as well as post-translational modifications of RyR channels. The company’s proprietary drugs, known as Rycals, are a new class of oral agents that repair calcium leaks through the RyR. 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.

For more information, please visit http://www.armgo.com or contact:

Media contact

Zyme Communications
Sarah Jeffery
Tel: +44 (0)7771 730919
E-mail: sarah.jeffery@zymecommunications.com

ARMGO Pharma Inc.
E-mail: info@armgo.com

• Series B investment led by Forbion and joined by Pontifax and Kurma Partners
  
• Investment will fund clinical studies of ARMGO’s lead molecule ARM210, an oral treatment, in development for cardiac and skeletal muscle diseases 

New York, USA – December 20 2021: ARMGO Pharma Inc (“ARMGO”), a leading novel small molecule therapeutics company developing treatments for cardiac, musculoskeletal, and neurological disorders today announced that it has completed a $35 million financing led by Forbion. Proceeds will fund further clinical development of its lead asset, ARM210, for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) as well as other cardiac and skeletal muscle indications. 

Forbion is a dedicated European life sciences venture capital firm that manages over €1.8 billion of investments and works closely with entrepreneurs to build life sciences companies that will change the future of medicine. In the financing, Forbion was joined by further top VC investors Pontifax and Kurma Partners. 

Dr. Geert-Jan Mulder and Dr. Dmitrij Hristodorov from Forbion, Dr. Iyona Rajkomar from Pontifax and Dr. Peter Neubeck from Kurma will join the ARMGO Board of Directors.  

The investment will fund Phase 2 clinical studies, commencing later this year, to evaluate ARM210 for the treatment of CPVT, a rare form of ventricular tachycardia and sudden death caused by mutations in the ryanodine receptor 2 (RyR2) which controls Ca2+ homeostasis in cells. Based on the work of ARMGO’s founder, Professor Andrew Marks from Colombia University, it is known that mutated RyR2 channels become leaky and lead to a severe form of ventricular arrhythmia. The current cornerstone therapy for CPVT is beta-blockers that reduce heart rate but do not repair the leaky channels that cause the arrythmia seen in most cases of CPVT. Beta-blockers leave a significant proportion of patients with residual arrhythmic burden that increases the risk for sudden cardiac death. Regardless of their efficacy, beta-blockers also cause strong side effects that significantly reduce the quality of life of these patients. To address both unmet needs, ARM210, a potentially disease-modifying, once daily oral pill, that repairs leaky RyR2 channels and restores physiological Ca2+ homeostasis will be tested in CPVT patients. ARM210 has successfully passed extensive preclinical development and human safety studies and is considered efficacious and well tolerated.  

ARMGO will initially aim to develop ARM210 in CPVT to provide a positive clinical proof-of-concept for the mechanism of action which will further de-risk the development of ARM210 in other diseases that are driven by dysregulated Ca2+ homeostasis. These studies will build on an ARM210 Phase 1b trial in patients with mutations in RyR1 (RyR1 related myopathy) ongoing at the National Institute of Health. Proceeds from the financing will be allocated to select further cardiac and skeletal muscle indications, ultimately building a pipeline-in-a-product for ARM210.  

Gene Marcantonio MD PhD, President and Chief Medical Officer of ARMGO, commented:
“We are pleased to have Forbion leading this financing round alongside Pontifax and Kurma Partners. They are all experienced healthcare investors that see the potential of ARMGO’s approach to provide disease-modifying treatments for patients by restoring the physiological Ca2+ homeostasis in affected tissues. We are excited to drive development of ARM210 in multiple indications and for the potential to reach significant milestone achievements within the next two years.”  

Geert-Jan Mulder and Dmitrij Hristodorov from Forbion commented: “We are pleased to lead this financing round and look forward to working together with Gene Marcantonio, his team and our co-investors in restarting and building ARMGO to reach potential clinical value inflection points over the coming years. ARMGO has done an excellent job in de-risking ARM210 through preclinical and early clinical development activities and it is now ready to be tested in patients.” 

Dr. Peter Neubeck of Kurma added: “We are excited to join the ARMGO team, Forbion and Pontifax in advancing ARMGO’s unique approach of modulating ryanodine receptors to treat high unmet need diseases with CPVT being an ideal initial clinical proof-of-concept indication.” 

-Ends- 

About Forbion www.forbion.com 

Forbion is a dedicated life sciences venture capital firm with offices in The Netherlands, Germany and Singapore. Forbion invests in life sciences companies that are active in the (bio-) pharmaceutical space. 

Forbion manages well over EUR 1.8 billion across multiple fund strategies that cover all stages of (bio-)pharmaceutical drug development. Forbion’s current team consists of 20 life sciences investment professionals that have built an impressive performance track record since the late nineties with successful investments in over 70 companies. The firm is a signatory to the United Nations Principles for Responsible Investment. Besides financial objectives, Forbion selects investments that will positively affect the health and well-being of patients. Its investors include the EIF, through its European Recovery Programme (ERP), LfA, Dutch Venture Initiative (DVI), AMUF and EFSI facilities and KfW Capital through the Programme, “ERP – Venture Capital Fonds investments”. Forbion operates a joint venture with BGV, the manager of seed and early-stage funds, especially focused on Benelux and Germany.  

About Kurma Partners www.kurmapartners.com 

Founded in July 2009, Kurma Partners is key European player in the financing of innovation in healthcare and biotechnology, from pre-seed to growth capital, notably through Kurma Biofund I through III and Kurma Diagnostics, as well as via strategic partnerships with prestigious European research and medical institutions. Innovative projects from Academia and research institutions, aspiring to meet unmet medical need is an important pillar of the firm’s investment strategy, a second is venture capital financings of innovative young companies in Biotech and MedTech; all with a strong focus on innovative drug development approaches. 

ARDSLEY, N.Y., December 17, 2019 –ARMGO Pharma, Inc., a clinical stage biopharmaceutical company advancing a novel class of small molecule drugs known as Rycals®, announced today the start of a clinical trial using its Rycal ARM210 (also known as S48168), for the treatment for patients with Ryanodine Receptor Type 1 Related Myopathies (RYR1-RM). The trial is being performed in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH). In 2018, the FDA granted orphan drug designation to ARMGO for ARM210 as a potential treatment for patients with RYR1-RM.  

ARM210 is a potential disease modifying therapy for genetic diseases, that targets the Ryanodine Receptor calcium channel (RyR), an intracellular calcium-release channel that becomes leaky in these and other diseases. Intracellular calcium leaks via 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.  

ARM210 is a small molecule that binds to leaky RyR channels and repairs the leak, as demonstrated in vitro in muscle biopsies from RYR1-RM patients. The unique mechanism of action of ARM210 makes it an ideal potential disease modifying therapy for RYR1-RM. Muscle biopsies of the patients in this trial have been previously shown to respond biochemically to ARM210 in vitro. This trial will evaluate the safety and explore the biochemical effect of oral administration of ARM210 in these same patients.  

“This trial represents an important achievement for the Rycal® ARM210 program as we hope to provide effective treatment for patients with RYR1-RM, for which there are no approved therapies,” said Gene Marcantonio MD PhD, President and Chief Medical Officer of ARMGO Pharma. “We are looking forward to continuing the progress of the ARM210 clinical program, building on success in RYR1-RM patients to address other genetic mutations of RYR 1 and 2.” Further information can be found at https://clinicaltrials.gov/ Identifier: NCT04141670. 

ARDSLEY, N.Y., September 5, 2018 –ARMGO Pharma, Inc., a clinical stage biopharmaceutical company advancing a novel class of small molecule drugs known as Rycals®, announced today that the  U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ARM210 (also known as S48168), a potential treatment for patients with Ryanodine Receptor Type 1 Related  Myopathies (RYR1-RM). In 2015, the FDA granted orphan drug designation and rare pediatric disease designation to ARM210 as a potential treatment for Duchenne Muscular Dystrophy (DMD).  

ARM210 targets the Ryanodine Receptor calcium-release channel(RyR), an intracellular calcium release channel that becomes leaky in a number of diseases including DMD and RYR1-RM, contributing to muscle damage and loss of function. RYR1-RM comprise a group of rare skeletal muscle diseases due to mutations in the ryr1 gene, which lead to leaky channels. These leaks both impair muscle contraction leading to muscle weakness and loss of function, and activate toxic pathways that damage muscle,  causing the symptoms in RYR1-RM. 

ARM210 is a small molecule that binds to leaky RyR channels and repairs the leak, as demonstrated in vitro in muscle biopsies from RYR1-RM patients. The unique mechanism of action of ARM210 makes it an ideal potential therapy for RYR1-RM.  

“This designation represents an important achievement for the Rycal® ARM210 program and highlights the unmet need to provide effective treatment for patients with RYR1-RM,” said Gene Marcantonio MD Ph.D., President and Chief Medical Officer of ARMGO Pharma. “We are looking forward to continuing  the progress of the ARM210 clinical program, including upcoming studies in RYR1-RM patients.” 

About Orphan Drug Designation  

Orphan Drug Designation is granted by the FDA to drug candidates intended to treat diseases affecting fewer than 200,000 patients in the U.S. Orphan designation qualifies the sponsor to apply for FDA  orphan research grants, waiver of Prescription Drug User Fee Act filing fees, tax credits for clinical research costs, and a seven-year period of market exclusivity upon approval of the drug.  

About ARMGO Pharma 

ARMGO Pharma, Inc., is a privately held biopharmaceutical company dedicated to applying targeted mechanism-based science to the development of novel small-molecule therapeutics to treat cardiac,  musculoskeletal, and neurological disorders. The company’s proprietary drugs, known as Rycals®, are a  new class of oral agents that repair the calcium leak through the RyR, which is located on the sarcoplasmic/endoplasmic reticulum. ARMGO Pharma has been awarded an exclusive, worldwide license from Columbia University for its RyR technology. Development and commercial rights for  ARMGO’s Rycal drugs in cardiovascular and skeletal muscle indications outside of the US and Japan are exclusively licensed to Les Laboratoires Servier (Servier). Development of ARM210 has been supported through a research collaboration with Servier, and an award from the Muscular Dystrophy  Association (MDA USA).