London, UK, 16th June 2026. Istesso, the leader in oral regenerative medicine, today announces the initiation of dosing in IST-03, a Phase 2 clinical trial of its lead candidate, leramistat.
The randomised, double-blind, placebo-controlled study is evaluating the effects of leramistat on muscle quality, repair and function in a targeted population of patients with sarcopenia (muscle-loss) caused by rheumatoid arthritis (RA).
Leramistat is the lead candidate from Istesso’s novel class of Mitochondrial Complex I Modulators (MCMs), which have demonstrated the ability to induce adaptive tissue repair and regeneration across multiple tissues, including muscle, bone, gut and lung.
The study builds directly on clinical data from prior RA trials in which leramistat improved disability and fatigue and reduced markers of sarcopenia, supported by preclinical data demonstrating its ability to improve muscle quality and function.
“We’re delighted to initiate IST-03,” said Lisa Patel, CEO of Istesso. “This trial marks an important step in translating leramistat’s regenerative mechanism into clinical benefits for patients with sarcopenia. By harnessing the body’s own adaptive repair mechanisms, we aim to move beyond symptom management and help people stay active and independent for longer.”
“IST-03 is a very exciting study to be involved in, with the potential to deliver meaningful improvements in muscle health for people living with rheumatoid arthritis,” said Dr Josh Bennett, Investigator at Newcastle University. “I look forward to exploring how leramistat’s novel mechanism of action influences skeletal muscle and the valuable insights muscle biopsies will provide into its effects at the tissue level.”
Up to a third of people aged over 60 are estimated to suffer from sarcopenia.[1],[2],[3] Affected individuals lose skeletal muscle strength, physical function and mass, leading to increased risk of falls and fractures and higher mortality.[4] Sarcopenia is also common across multiple chronic diseases including rheumatoid arthritis [5], Alzheimer’s disease[6], heart failure [7] and fibrosis.[8],[9] However, there are no specific medicines available to treat it.
Leramistat offers the potential to alter the trajectory of sarcopenia and multiple age-related diseases by repairing underlying tissue degeneration. Enrolment is currently underway at Newcastle University and Newcastle Hospitals, in conjunction with the National Institute for Health and Care Research (NIHR) whose specialist facilities and biopsy expertise include advanced imaging and analysis techniques that are ideally suited to delivering this innovative trial.
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Notes to editors
About leramistat
Leramistat is an investigational first-in-class oral regenerative medicine which is currently Phase 2 development for musculoskeletal repair in secondary sarcopenia. It is a novel mitochondrial Complex I modulator (MCM), and its unique MOA augments the body’s inherent capacity to repair, restoring damaged tissue and building resilience without suppressing the immune system.[10],[11] Leramistat has been shown to reduce the progression of structural damage, improve CRP, disability and fatigue, and reduce markers of muscle loss in clinical trials.11
Leramistat offers the potential for disease resolution across a wide range of therapeutic areas including primary and secondary sarcopenia, bone and metabolic disorders, and chronic diseases of auto-inflammation, autoimmunity and fibrosis.10,11 Leramistat has been granted both FDA Fast Track and Orphan Drug Designation (ODD) to support its development and expedite its review to fill an unmet medical need in idiopathic pulmonary fibrosis (IPF).
About muscle loss
Muscle loss, encompassing both age-related decline (primary sarcopenia) and disease/drug-related loss (secondary sarcopenia), represents a significant and growing global health challenge. Individuals affected show progressive decline of skeletal muscle quality, physical function and mass occurring as early as the third decade of life and accelerating above the age of 60, or with the diagnosis of chronic diseases such as rheumatoid arthritis,5 Alzheimer’s disease,6 heart failure,7 IPF8 or MAFLD.9 Sarcopenia affects approximately 110 million people globally, increasing the risk of falls, fractures, hospitalisation4 and posing a significant societal and economic burden.1,3 However, no specific pharmacologic therapies are currently available.
About tissue repair
In health and throughout life, our bodies maintain a natural equilibrium, constantly renewing cells and tissues in the body and balancing any damage that occurs with a natural capacity to repair.[12] As we age, capacity to repair diminishes and tissue damage accumulates, putting us at increased risk of chronic disease, which is the leading cause of illness, disability and premature death globally.[13],[14] Identifying a signal that can direct damaged tissues to regenerate and repair has been a critical goal of medicine.[15] Istesso’s investigational treatments work in a completely new way, by enabling mitochondria – the beating heart of the body’s cells – to turn on the body’s ‘repair switch’. This augments the body’s natural ability to mobilise progenitor cells10, a type of stem cell which repair injuries and regenerate tissue, enhances tissue repair, and reduces tissue damage and inflammation in multiple models of disease and tissue types.10,11 This approach, leveraging and enhancing the body’s natural repair system, potentially offers powerful new tools, with a good safety profile, to support tissue repair, resolve disease, and extend human healthspan.[16]
About Istesso
Istesso is developing pioneering oral regenerative medicines that enhance the body’s ability to repair, redefine treatment expectations and make a lasting impact on peoples’ lives. We stand apart, disrupting conventional thinking and seeking robust science-led treatment solutions to enable people to live free from chronic disease. Scientists at heart, with almost 1000 years of drug discovery expertise, we are the only company to understand and exploit the body’s natural biology of repair. To learn more please visit us at: www.istesso.co.uk
About the National Institute for Health and Care Research (NIHR):
The mission of the NIHR)is to improve the health and wealth of the nation through research. NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.
About Newcastle University
Newcastle University, UK, is a thriving international community of more than 28,000 students from over 130 countries worldwide. As a member of the Russell Group of research-intensive universities in the UK, Newcastle has a world-class reputation for research excellence in the fields of medicine, science and engineering, social sciences and the humanities.
For more information, please contact
Istesso media relations:
Email: stuart@lolly-agency.co.uk
Tel: 01935 816 400
References
[1] Kirk B et al. Global consensus for sarcopenia. Aging (Albany NY). 2024;16(11):9306-9308.
[2] World Health Organization. Question and answers: Ageing: Global population; updated 21 February 2025. Available at: https://www.who.int/news-room/questions-and-answers/item/population-ageing Last accessed November 2025.
[3] Petermann-Rocha F, et al. Global prevalence of sarcopenia and severe sarcopenia: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022;13(1):86-99
[4] Cruz-Jentoft AJ et al, Sarcopenia: revised European consensus on definition and diagnosis, Age and Ageing. 2019, 48 (1): 16–31
[5] Moschou D et al. Sarcopenia in Rheumatoid arthritis. A narrative review. J Frailty Sarcopenia Falls, 2023;8(1):44-52
[6] Kim J et al. Sarcopenia is a predictor for Alzheimer’s continuum and related clinical outcomes. Sci Rep 2024;14: 21074
[7] Iyer L et al. Prevalence of sarcopenia in heart failure: A systematic review. Indian Heart Journal, 2023; 75(1):36-42
[8] Zeng J et al. Sarcopenia in idiopathic pulmonary fibrosis: an updated systematic review and meta-analysis Frontiers in Medicine, 2025;12:1681237
[9] Zhao Q et al. Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study. Nutr. Diabetes, 2023;13: 21
[10] Patel L et al. Phenotypic Pharmacology of Novel Complex I Inhibitors Eliciting Tissue Repair Concurrent to Control of Inflammation. JPET. 2025; 392: 103661
[11] Data on file
[12] Cai Y et al. Decoding aging-dependent regenerative decline across tissues at single-cell resolution. Cell Stem Cell 2023; 30(12); 1674
[13] Martin P et al. Imperfect wound healing sets the stage for chronic diseases. Science. 2024; 386,eadp2974
[14] World Health Organization. Factsheet: Noncommunicable diseases. September 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases. Last accessed April 2025.
[15] McKinley, K et al Emerging frontiers in regenerative medicine Science 2023 380 (6647):796-798
[16] Ukraintseva S et al. Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity. Mechanisms of Ageing and Development. 2021; 194:111418
