Ground-breaking data demonstrate tissue repair with portfolio company, Istesso's novel investigational medicines.

Dr Mike Owen now appointed to Istesso's Board of Directors

IP Group plc (LSE: IPO) announces that its portfolio company Istesso Ltd ("Istesso") has today published ground-breaking data in the peer reviewed monthly, The Journal of Pharmacology and Experimental Therapeutics (JPET), demonstrating its new class of investigational medicines elicit tissue repair in fibrotic, autoinflammatory and autoimmune conditions - the first oral agents to demonstrate such activity.

These findings have significant implications for the management of chronic diseases where tissue damage occurs, including chronic diseases such as rheumatoid arthritis, degenerative conditions of ageing such as osteoporosis, sarcopenia (muscle loss) and fibrosis (tissue scarring), and could herald a new era of treatments to minimise the impact of these conditions on people's lives.

Dr Lisa Patel, lead study author and Istesso's CEO, said: "These findings could redefine how we think about treating chronic diseases. Eliciting tissue repair has long been a goal of medicine. This is the first time adaptive tissue repair has been demonstrated with oral agents in these settings. We are very excited to be pioneering this game-changing new field, offering a novel path to stopping, or even reversing, progressive tissue decline."

The announcement from Istesso follows below. Further results from Istesso's research programme will be presented at relevant congresses and published in peer review journals in due course.

Separately, Istesso also recently announced the appointment of Dr Mike Owen to its Board of Directors as a non-executive director with immediate effect. Dr Owen brings over 40 years' experience in the pharmaceutical and biotechnology industries and has extensive expertise leading drug discovery and development, in particular identifying the clinical and commercial positioning of novel drugs. Dr Owen started his industry career at GSK, where he was Senior Vice President (SVP) and Head of Biopharmaceuticals Research from 2001 to 2009. During this time, he was accountable for a biopharmaceuticals portfolio comprising over twenty projects in multiple therapeutic areas, including clinical Phase 1 and 2 assets in diseases of major unmet medical need such as cancer, Alzheimer's, motor neurone disease, severe asthma and rheumatoid arthritis.

Dr Owen said: "I'm very happy to be joining Istesso at this important time. I have been following Istesso's bold approach to reversing tissue damage with great interest. Its promising scientific research into this currently untapped area has the potential to fundamentally change the treatment paradigm for chronic diseases and therefore holds enormous clinical and commercial potential. I can't wait to get started in helping Istesso accelerate the development of its investigational lead drug leramistat."

IP Group has an undiluted holding of 56.5% in Istesso.

For more information, please contact:

Notes for editors

About IP Group

IP Group accelerates the impact of science for a better future. As the most active UK based, early stage science investor, we develop and support some of the world's most exciting businesses in deeptech, life sciences and cleantech (led by Kiko Ventures). Through Parkwalk, the UK's largest growth EIS fund manager, we also back world-changing innovation emerging in leading universities and research institutions. Our specialist investment team combines sector expertise with an international approach. Together we have a strong track record of success, having backed high-profile companies including Oxford Nanopore Technologies plc, Featurespace, First Light Fusion, Hysata, and Oxa. IP Group is listed on the Main Market of the London Stock Exchange under the code IPO. For more information, please visit our website at www.ipgroupplc.com.

ENDS

Ground-breaking data demonstrates tissue repair with Istesso's novel investigational medicines

·    Istesso's new class of developmental drugs, which inhibit mitochondrial complex I, are the first to elicit tissue repair in fibrotic, autoinflammatory and autoimmune conditions.^1,2

·    The unique mechanism of action (MOA) means these drugs also have the potential to slow progressive age-related decline and build resilience against the accumulation of age-related tissue damage, helping us to age better and live longer.^{1,3, 4}

·    These findings have significant implications for the management of chronic diseases where tissue damage occurs, including chronic autoimmune diseases such as rheumatoid arthritis (RA), degenerative conditions of ageing such as osteoporosis, sarcopenia (muscle loss) and fibrosis (tissue scarring), and could herald a new era of treatments to minimise the impact of these conditions on people's lives.^{1,2, 5, 6}  

London, UK, 16^th July 2025. Published today in peer reviewed monthly, The Journal of Pharmacology and Experimental Therapeutics (JPET), Istesso, the adaptive tissue-repair company, reveals data showing that its novel, first-in-class mitochondrial Complex I inhibitors elicit tissue repair in models of autoimmune and fibrotic disease.¹ Istesso's novel approach works in a completely new way; by modulating mitochondria - the beating heart of the body's cells - to support the body's repair systems.¹ In doing so, it enhances tissue repair, augments the body's natural ability to mobilise progenitor cells,¹ a type of stem cell which repair injuries and regenerate tissue, and reduces tissue damage and inflammation in models of arthritis and lung scarring.^1,2

"These findings could redefine how we think about treating chronic diseases," said Dr Lisa Patel, lead study author and Istesso's CEO. "Eliciting tissue repair has long been a goal of medicine. This is the first time adaptive tissue repair has been demonstrated with oral agents in these settings. We are very excited to be pioneering this game-changing new field, offering a novel path to stopping, or even reversing, progressive tissue decline."

Tissue damage occurs in nearly every human illness and is a universal feature of ageing.7^,8 Accumulating tissue damage also predisposes to chronic disease, which is the leading cause of illness, disability and premature death globally.^5,6 Whilst traditional medicines such as anti-inflammatory drugs used to treat conditions like RA and inflammatory bowel disease (IBD) are effective in treating symptoms, they do not support, and may suppress, the body's natural repair processes.9^,10 The novel biological effects seen with Istesso's pipeline of treatments could offer the potential to directly prevent or even potentially reverse progressive tissue decline in multiple chronic diseases such as RA or IPF, or in degenerative conditions such as muscle or bone loss (sarcopenia and osteoporosis).^{11, 12, 13,14, 15}

"This work opens a new chapter in mitochondrial pharmacology" commented Professor Sir Keith Peters, Regius Professor of Physic Emeritus, and Non-executive Board Director, Istesso.

Early findings suggest that this biology may be replicated in the clinic. Istesso's lead investigational medicine, leramistat has consistently demonstrated its effectiveness in preventing tissue deterioration.^1,2,16 In Phase 2 clinical studies (yet to be published), RA patients given leramistat showed significantly improved bone erosions, disability and fatigue responses, as well as improvements in markers of inflammaging (chronic inflammation associated with ageing) such as C-Reactive Protein (CRP), and of changes in mitochondrial function such as Growth Differentiation Factor 15 (GDF15) and Fibroblast Growth Factor 21 (FGF21).² Treatment with leramistat also improved the balance between bone formation and loss which is disrupted in RA.² This encouraging profile has been accompanied by good toleration and a benign adverse event (AE) profile with no serious AEs attributed to treatment in any studies to date.²

Further results from our research programme will be presented at relevant congresses and published in peer review journals in due course. 

- Ends -

Notes to editors

JPET publication

The Journal of Pharmacology and Experimental Therapeutics (JPET), is the official journal of the American Society for Pharmacology and Experimental Therapeutics and the full publication can be accessed here: https://doi.org/10.1016/j.jpet.2025.103661

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 ranging from genetic disorders that affect how mitochondria are made, to 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.^17,18,19 When mitochondria experience a change in their function, they release proteins such as GDF15 or FGF21 which signal the change into their environment.²⁰

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.⁷  As we age, this process deteriorates putting us at increased risk of chronic diseases which in turn contribute to further progressive tissue damage and reduce the body's natural capacity to repair.^4,5,7 This has led to the hypothesis that longevity may result from the ability to sustain this tissue renewal process.^10,20 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.^6,9 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.^{21, 22, 23}

Identifying a signal that can direct damaged tissues to regenerate and repair is a critical goal of medicine which has remained elusive until now.³ Istesso's investigational treatments work in a completely new way, turning on the body's 'repair switch' to enable the repair of damaged tissue and restore tissue architecture to its original form.^1,2 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.⁴

About rheumatoid arthritis (RA)

RA is a destructive chronic and debilitating autoimmune disease causing severe joint and tissue damage that can lead to disability and premature death affecting approximately 17.6 million people globally.^{24, 25} This figure is expected to double to ~31.7 million by 2050 and it is estimated that ~70% of those affected will be female.²⁴ Bone erosions appear early in the course of RA, often preceding diagnosis and up to 60% of patients have erosions within a year leading to joint damage and causing impaired function and disability.^{26, 27, 28} Even with significant treatment advances, many patients continue to show joint deterioration and disability, and rates of RA related surgery remain relatively unchanged in many countries.^{29, 30} 

The majority of people with RA also experience daily fatigue with significant overwhelming exhaustion affecting up to 70% of patients, and almost three-quarters experiencing persistently high or worsening levels of fatigue.^{30, 31} Fatigue is a key contributor to increased clinical care costs, primary care consultations and employment loss, and is poorly understood and managed. Current treatments have a minimal effect on fatigue.²⁴

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 inhibitor of mitochondrial Complex I, 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 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.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 Istesso

Istesso is looking at chronic disease differently, focusing on repairing the damage caused by debilitating chronic conditions rather than symptom control. We stand apart, disrupting conventional thinking and seeking robust science-led treatment solutions to enable patients 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, redefine treatment expectations and make a lasting impact on patients' 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

1.     Patel L et al. Phenotypic Pharmacology of Novel Complex I Inhibitors Eliciting Tissue Repair Concurrent to Control of Inflammation.  JPET. 2025; https://doi.org/10.1016/j.jpet.2025.103661

2.     Data on file

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

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12.  Ringe J, Regenerative medicine in rheumatic disease-progress in tissue engineering. Nat Rev Rheumatol. 2012; 8(8):493-8.

13.  Lehmann M, Regenerative Medicine and the Hope for a Cure. Clin Chest Med. 2021; 42(2):365

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15.  Arjmand B, Prospect of Stem Cell Therapy and Regenerative Medicine in Osteoporosis. Front Endocrinol (Lausanne). 2020; 3;11:430

16.  Patel L,  et al. OP0234  MBS2320, A novel selective modulator of immune metabolism, in patients with severe rheumatoid arthritis: safety, tolerability and efficacy results of a phase 2 study. Annals of the Rheumatic Diseases. 2020; 79

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18.  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.

19.  Li X et al., Mitochondrial dysfunction in fibrotic diseases. Cell Death Discov. 2020; 6:80

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21.  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

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

23.  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

24.  Black RJ et al. Global regional, and national burden of rheumatoid arthritis, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023; 5(10):e594-e610.

25.  World Health Organization. Factsheet: Rheumatoid arthritis; updated 28 June 2023.  Available at: https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis  Last accessed April 2025.

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28.  Pap T et al. Cartilage damage in osteoarthritis and rheumatoid arthritis--two unequal siblings.  Nat Rev Rheumatol. 2015; 11(10):606-15.

29.  Tominaga A et al. Surgical intervention for patients with rheumatoid arthritis is declining except for foot and ankle surgery: A single-centre, 20-year observational cohort study. Modern Rheumatology.  2023; 33(3):509-516.

30.  Dures E et al.  2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.  Annals of the Rheumatic Diseases. 2024; 83:1260-1267

31.  Druce KL et al. Predictors of fatigue in rheumatoid arthritis.  Rheumatology. 2019; 58(5):v29-v34.