- Advancement of leramistat, a first-in-class mitochondrial complex I modulator (MCM), into musculoskeletal repair.[i],[ii]
- Nomination of new development candidate, MBS2687.
London, UK, 26th November 2025. Istesso, the leader in adaptive tissue repair and regeneration, today provides updates for its lead program, leramistat, and pipeline.
Following the results of its recent Phase 2b clinical trial in rheumatoid arthritis (RA), Istesso is refocussing the development of leramistat on musculoskeletal repair. Alongside the compelling evidence of leramistat’s ability to protect bone and improve disability and fatigue responses in patients with RA, further analysis of the study data has revealed signs of a muscle-protective effect. These include improvements in physical functions requiring large muscle movement as well as a decrease in levels of a key biomarker of muscle loss, C-terminal agrin (CAF-22).
More than 110 million patients worldwide are estimated to suffer from muscle loss, clinically defined as sarcopenia. [iii],[iv] Affected individuals show progressive decline of skeletal muscle mass, strength and physical function leading to increased risk of falls and fractures, and higher mortality. [v],[vi] Occurring as early as the third decade of life and accelerating above the age of 60, muscle loss is a key feature of ageing, and poses a significant societal and economic burden. However, no specific pharmacologic therapies are currently available.
“The potential of leramistat to directly target the muscle is hugely exciting, suggesting that the breadth of settings in which we have observed repair preclinically may be achievable in humans,” said Dr Lisa Patel, Istesso’s CEO “This confirms our view that our novel MCMs offer a novel path to stopping, or even reversing, progressive tissue decline to restore and extend health.”
Leramistat’s protective effects on both bone and muscle position it for potential use as a musculoskeletal protective agent with application across a range of degenerative age-related conditions, including sarcopenia (muscle loss), osteoporosis and osteosarcopenia. In addition, in RA, leramistat offers the potential to create novel combinations with existing drugs to halt or reverse disability progression and deepen disease control.
Beyond leramistat, Istesso continues to develop its novel, proprietary class of MCMs and, in this respect, has nominated MBS2687 as a development candidate. MBS2687 is an orally available, small-molecule MCM with best-in-class potential. Further results from Istesso’s research programmes will be presented at relevant congresses and published in peer review journals in due course.
– Ends –
Notes to editors
About mitochondria
Mitochondria, often referred to as the powerhouses of the cell, are present in nearly all types of human cell and are vital to our survival. They perform many different functions including generating energy to power cells, regulating metabolism and playing a key role in cell responses to infection and injury and signalling between cells and tissues. Damage or disruption to mitochondrial signalling underlies many human diseases including age-related degenerative disorders such as sarcopenia, osteoporosis, and Alzheimer’s disease, autoimmune diseases such as RA and IBD, and fibrotic diseases such as IPF or heart failure.[vii],[viii],[ix] When mitochondria experience a change in their function, they release proteins such as GDF15 or FGF21 which signal the change into their environment.[x]
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.[xi] 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.[xii],[xiii] This has led to the hypothesis that longevity may result from the ability to sustain this tissue renewal process.x,[xiv], 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.xiii,[xv], 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.[xvi],[xvii],[xviii]
Identifying a signal that can direct damaged tissues to regenerate and repair is a critical goal of medicine which has remained elusive until now.[xix] 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,i 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.i, ii 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 and ultimately resolve disease, and extend human healthspan.[xx]
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 mass, strength and physical function 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, COPD or MASH. This loss is associated with increased risk of falls, fractures, hospitalisation and higher mortality.[xxi] The condition affects approximately 110 million people globally and poses a significant societal and economic burden.[xxii],[xxiii],[xxiv] However, no specific pharmacologic therapies are currently available.
A key factor in the development and progression of sarcopenia is loss of neuromuscular junctions, key structures which maintain nerve-muscle communication. C-terminal agrin fragment (CAF) is a circulating biomarker which is formed during the remodelling of neuromuscular junctions. A growing body of evidence supports the use of CAF as a biomarker of sarcopenia.xxiv
About leramistat
Leramistat is an investigational first-in-class, once-daily pill currently in phase 2 development where it is being evaluated for its potential to elicit 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.i,ii Leramistat has been shown to reduce the progression of structural damage, improve disability and fatigue and improve inflammaging (CRP) in people with RA, where it offers the potential to target aspects of the condition that remain unmet by current therapies.ii
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.i,ii 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 Istesso
Istesso is restoring biological harmony to extend healthspan. 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. Istesso is discovering and developing pioneering transformative medicines that enhance the body’s ability to repair and regenerate, redefine treatment expectations and make a lasting impact on peoples’ lives. To learn more please visit us at: www.istesso.co.uk
For more information, please contact
Istesso media relations:
Email: stuart@lolly-agency.co.uk
Tel: 01935 816 400
References
[i] Patel L et al. Phenotypic Pharmacology of Novel Complex I Inhibitors Eliciting Tissue Repair Concurrent to Control of Inflammation. JPET. 2025; 392: 103661
[ii] Data on file
[iii] Kirk B et al. Global consensus for sarcopenia. Aging (Albany NY). 2024;16(11):9306-9308.
[iv] 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.
[v] 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
[vi] Cruz-Jentoft AJ et al, Sarcopenia: revised European consensus on definition and diagnosis, Age and Ageing, 2019, 48 (1): 16–31
[vii] Pei, L et al., Mitochondria in skeletal system-related diseases. Biomedicine & Pharmacotherapy,
2024;181:117505
[viii] University of Cambridge. MRC Mitochondrial Biology Unit. What are Mitochondria. Available at: https://www.mrc-mbu.cam.ac.uk/what-are-mitochondria/mitochondria-disease. Last accessed April 2025.
[ix] Li X et al., Mitochondrial dysfunction in fibrotic diseases. Cell Death Discov. 2020; 6:80
[x] Jena J. The roles of FGF21 and GDF15 in mediating the mitochondrial integrated stress response. Front Endocrinol (Lausanne). 2023; 14:1264530
[xi] Cai Y et al. Decoding aging-dependent regenerative decline across tissues at single-cell resolution. Cell Stem Cell 2023; 30(12); 1674
[xii] Martin P et al. Imperfect wound healing sets the stage for chronic diseases. Science. 2024; 386,eadp2974
[xiii] 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.
[xiv] Fischer, R, Selective Targeting of TNF Receptors as a Novel Therapeutic Approach. Frontiers in Cell and Developmental Biology. 2020; 8:401
[xv] Bootun R, Effects of immunosuppressive therapy on wound healing. Int Wound J. 2013; 10(1):98-104.
[xvi] 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
[xvii] Pharmaphorum IPF: Could we reverse the progression? https://pharmaphorum.com/rd/ipf-could-we-reverse-progression Last accessed June 2025
[xviii] 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
[xix] McKinley, K et al Emerging frontiers in regenerative medicine Science 2023 380 (6647):796-798
[xx] 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
[xxi] Cruz-Jentoft AJ et al, Sarcopenia: revised European consensus on definition and diagnosis, Age and Ageing, 2019, 48 (1): 16–31
[xxii] 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
[xxiii] Kirk B et al. Global consensus for sarcopenia. Aging (Albany NY). 2024;16(11):9306-9308.
[xxiv] Fatima R et al. C-Terminal Agrin Fragment as a Biomarker for Sarcopenia: A Systematic Review and Meta-Analysis. J Cachexia Sarcopenia Muscle. 2025;16:e13707
