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• Leramistat, a first-in-class mitochondrial complex I modulator (MCM),[1],[2] improves muscle quality and function and protects muscle mass in mouse models of aging and inflammation.
• In aged mice, leramistat increased muscle quality and function to levels greater than those of younger mice at baseline. In a model of inflammatory muscle loss, it restored muscle quality and mass to levels seen in healthy, non-diseased controls.2
• Data support the potential of leramistat to treat muscle loss (sarcopenia) in aging and multiple chronic disease settings.

London, UK, 21st April 2026. Istesso, the leader in oral regenerative medicine, today announces it will present preclinical data on the potential of leramistat to treat sarcopenia due to aging and chronic disease at the 9th World Congress on Aging and Geriatrics (WCAG-2026), to be held on September 16-17th in Berlin.

Up to a third of people aged over 60 are estimated to suffer from sarcopenia.[3],[4],[5] Affected individuals lose skeletal muscle strength, physical function and mass, leading to increased risk of falls and fractures and higher mortality.5[6] Sarcopenia is a hallmark of aging and is also common across multiple chronic diseases including rheumatoid arthritis[7], Alzheimer’s disease[8] heart failure[9] and fibrosis.[10],[11] However, there are no specific medicines available to treat it.

Leramistat improved muscle quality, as assessed by fibre mass and typing, in two models of muscle loss. In the collagen-induced arthritis model of inflammatory muscle loss, it restored fibre mass and quality to that of naïve, healthy mice. In aged (23-month-old) mice, leramistat returned fibre mass, quality and function – as assessed by grip strength – to levels greater than those seen in baseline younger mice.

“The capacity of muscle to function, measured by grip strength, is one of the strongest predictors of overall health, independence and survival,” said Dr Lisa Patel, Istesso’s CEO. “These data are striking: leramistat not only protected and restored muscle in models of aging and chronic inflammation, but in aged mice it drove quality and function beyond that of younger animals at baseline. Combined with our clinical data showing improvements in disability, fatigue and bone protection in rheumatoid arthritis, leramistat offers the potential to alter the trajectory of sarcopenia and multiple age-related diseases – helping people to live physically independent and active for longer.”

Two presentations will be made on 16th September in the session “Anti-aging strategies and drug development”:

• “Leramistat, a first-in-class mitochondrial Complex I modulator, protects muscle mass and improves muscle quality in mice with collagen-induced arthritis”
• “Induction of an integrated stress response and improvement in muscle quality and function by leramistat, a first in class mitochondrial Complex I modulator”.

Summary of key findings:

• Leramistat, a first-in-class MCM, protects muscle mass and improves muscle quality in a collagen-induced arthritis (CIA) model of degenerative inflammation-associated muscle loss, reaching levels seen in age-matched, healthy controls.
• In age-associated muscle loss (23- to 26- month-old mice), leramistat significantly ameliorates degenerative pathology and improves grip strength to beyond levels observed in younger mice.
• In aged mice, leramistat elicits expansion of the muscle stem (satellite) cell niche, consistent with the creation of a regenerative microenvironment.

– Ends –

Notes to editors

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,7 Alzheimer’s disease,8 heart failure,9 IPF10 or MAFLD.11 Sarcopenia affects approximately 110 million people globally, increasing the risk of falls, fractures, hospitalization6 and posing a significant societal and economic burden.3,5  However, no specific pharmacologic therapies are currently available.

Grip strength is a primary diagnostic marker of sarcopenia and a surrogate marker for overall muscular strength and systemic health. Decline in grip strength is closely correlated with muscular strength and has been independently associated with frailty, as well as risk of all-cause and cardiovascular mortality. [12]

About leramistat

Leramistat is an investigational first-in-class, once-daily pill currently in phase 2 development for musculoskeletal repair in secondary sarcopenia. It is a novel modulator of mitochondrial Complex I (MCM), and its unique MOA augments the body’s inherent capacity to repair, restoring damaged tissue and building resilience without suppressing the immune system.1,2 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.2

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.1,2 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 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.[13] 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.[14],[15] This has led to the hypothesis that health may result from the ability to sustain this tissue renewal process.[16] Current treatment approaches and research focus on symptom control, usually by suppressing uncontrolled inflammation or fibrosis (tissue scarring) but do not support the body’s natural repair process.16,[17] As a consequence, disease-related damage persists and progresses, albeit at a slower rate than without treatment, and in some cases may drive further symptoms.[18],[19],[20]

Identifying a signal that can direct damaged tissues to regenerate and repair is a critical goal of medicine which has remained elusive until now.[21] Istesso’s investigational treatments work in a completely new way, by modulating mitochondria – the beating heart of the body’s cells – to turn on the body’s ‘repair switch’. This enhances tissue repair, augments the body’s natural ability to mobilise progenitor cells, a type of stem cell which repair injuries and regenerate tissue, and reduces tissue damage and inflammation in multiple models of disease and tissue types.1,2 This approach, leveraging and enhancing the body’s natural repair mechanisms, offers a powerful new approach to restore and extend human health.[22]

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

For more information, please contact

Istesso media relations:

Email: [email protected]

Tel: 01935 816 400 

References

[1] Patel L et al. Phenotypic Pharmacology of Novel Complex I Inhibitors Eliciting Tissue Repair Concurrent to Control of Inflammation.  JPET. 2025; 392: 103661

[2] Data on file

[3] Kirk B et al. Global consensus for sarcopenia. Aging (Albany NY). 2024;16(11):9306-9308.

[4] 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.

[5] 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

[6] Cruz-Jentoft AJ et al, Sarcopenia: revised European consensus on definition and diagnosis, Age and Ageing. 2019, 48 (1): 16–31

[7] Moschou D et al. Sarcopenia in Rheumatoid arthritis. A narrative review. J Frailty Sarcopenia Falls, 2023;8(1):44-52

[8] Kim J et al. Sarcopenia is a predictor for Alzheimer’s continuum and related clinical outcomes. Sci Rep 2024;14: 21074

[9] Iyer L et al. Prevalence of sarcopenia in heart failure: A systematic review. Indian Heart Journal, 2023; 75(1):36-42

[10] Zeng J et al. Sarcopenia in idiopathic pulmonary fibrosis: an updated systematic review and meta-analysis Frontiers in Medicine, 2025;12:1681237

[11] Zhao Q et al. Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study. Nutr. Diabetes, 2023;13: 21

[12] Leong D et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. The Lancet, 2015;386(9990):266-273

[13] Cai Y et al. Decoding aging-dependent regenerative decline across tissues at single-cell resolution. Cell Stem Cell 2023; 30(12); 1674

[14] Martin P et al. Imperfect wound healing sets the stage for chronic diseases. Science. 2024; 386,eadp2974

[15] 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.

[16] Fischer, R, Selective Targeting of TNF Receptors as a Novel Therapeutic Approach. Frontiers in Cell and Developmental Biology. 2020; 8:401

[17] Bootun R, Effects of immunosuppressive therapy on wound healing. Int Wound J. 2013; 10(1):98-104.

[18] Ruyssen-Witrand, A  et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023; 25:207

[19] Pharmaphorum IPF: Could we reverse the progression? https://pharmaphorum.com/rd/ipf-could-we-reverse-progression Last accessed June 2025

[20] Ahmad, HA et al. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther 2022; 24; 47

[21] McKinley, K et al Emerging frontiers in regenerative medicine Science, 2023;380(6647):796-798

[22] Vaishya R et al. Hand grip strength as a proposed new vital sign of health: a narrative review of evidences.  Journal of Health, Population and Nutrition.  2024; 43:7