New analyses point to muscle-protective effects for leramistat as Istesso expands its pipeline with next-generation mitochondrial modulators.
London-based biotech Istesso has delivered a significant strategic update, announcing new directions for its mitochondrial modulation platform and fresh evidence supporting the potential of its lead candidate, leramistat, in musculoskeletal repair.
The move follows detailed post-hoc analyses from a Phase 2b rheumatoid arthritis (RA) trial, which revealed signals far beyond joint inflammation, including bone protection and early signs of muscle preservation [1].
Leramistat, an oral first-in-class mitochondrial complex I modulator (MCM), is designed to activate the body’s intrinsic repair machinery. Now, Istesso believes it may have broader, system-level implications for age-related degenerative conditions.
Mitochondrial modulation as a repair strategy
Mitochondria, often described as the cell’s “powerhouses,” do far more than generate energy. They regulate cell stress, metabolism, communication, inflammation, and the body’s response to injury. When mitochondrial signals falter – a hallmark of aging – tissues lose their ability to repair themselves.
Istesso’s science aims to modulate these signals, effectively turning the body’s repair processes back on. The company’s MCMs have shown the ability to mobilize key progenitor cells, reduce inflammation, and enhance regenerative activity across multiple preclinical models.
This approach represents a shift from suppressing disease activity to restoring biological balance, a direction that fits squarely within the broader longevity and regenerative medicine landscape.
Signals of muscle protection strengthen clinical case
Following the completion of its RA study, the company analyzed deeper functional outcomes tied to large-muscle movement and found unexpectedly encouraging trends. Improvements in tasks requiring significant muscle engagement were accompanied by reduced blood levels of CAF-22, a circulating biomarker linked to neuromuscular junction breakdown and early muscle loss.
With more than 110 million people worldwide affected by sarcopenia, the progressive loss of muscle mass and strength, the implications are substantial. Muscle loss accelerates after age 60, raises the risk of falls and fractures, and significantly increases hospitalization and mortality. Yet no approved pharmacologic therapy exists. That unmet need is where Istesso sees an opening.
“The potential of leramistat to directly target the muscle is hugely exciting,” said Dr Lisa Patel, Istesso’s CEO. “This confirms our view that our novel MCMs offer a new path to stopping, or even reversing, progressive tissue decline.”
The company now plans to advance leramistat specifically in musculoskeletal repair, including age-related sarcopenia, osteoporosis and osteosarcopenia. In RA, leramistat may also be positioned as a combination therapy that complements existing anti-inflammatories and deepens disability control.
Expanding pipeline
Alongside the renewed push for leramistat, Istesso has also nominated MBS2687 as its newest development candidate [2]. MBS2687 is an orally available, small-molecule MCM with what the company describes as best-in-class potential.
While details remain limited, Istesso says additional data will be presented at upcoming scientific congresses and in peer-reviewed publications. For investors tracking the company’s platform, this marks a significant signal: Istesso is investing not just in a single drug, but in an entire class of mitochondrial-targeting repair therapeutics.
The concept behind Istesso’s pipeline is rooted in a simple but powerful idea that aging accelerates when repair slows down. As tissues accumulate damage faster than they can regenerate, chronic diseases take hold.
Most current treatments suppress inflammation or fibrosis, but do not restore the underlying regenerative balance. Istesso’s approach attempts to correct the root problem by reactivating innate repair pathways. If successful, such therapies may redefine expectations for chronic disease management and extend meaningful healthspan.
Positioning within the longevity and regenerative biotech landscape
There is growing investor interest in companies targeting the biology of regeneration, particularly those working upstream of traditional inflammatory pathways. Istesso’s strategy – combining a first-in-class candidate with a maturing platform of next-generation MCMs – positions it within a competitive but rapidly expanding sector of longevity biotech.
The company’s dual focus on age-related degeneration and autoimmune-driven tissue decline could broaden its commercial reach, especially as health systems grapple with the rising burden of aging populations.
With FDA Fast Track and Orphan Drug Designation (ODD) already secured for leramistat in idiopathic pulmonary fibrosis, regulatory momentum adds another point of confidence.
Istesso’s latest update highlights a quiet but meaningful shift in biotechnology – the move toward therapies that do not merely slow disease, but reactivate the body’s ability to repair itself. By refocusing leramistat on muscle and bone preservation and advancing new mitochondrial modulators like MBS2687, the company is aiming squarely at one of medicine’s most urgent challenges: the accelerating decline of human tissues with age.
It is an ambitious proposition, but suppose Istesso’s early signals translate into clinical success. In that case, the company may help define a new generation of regenerative therapeutics, one that treats aging as a biology that can be influenced, modulated and meaningfully improved.
[1] https://istesso.co.uk/istesso-provides-updates-on-leramistat-and-next-generation-programs/
[2] https://istesso.co.uk/our-pipeline/
