Pre-clinical development of a novel allosteric inhibitor of SRC kinase for spontaneous multi-joint osteoarthritis (OA) and OA-associated chronic pain

The National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded Reparris, Inc., $301,567 on September 1, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to support pre-clinical development of a novel allosteric inhibitor of SRC kinase for spontaneous multi-joint osteoarthritis and OA-associated chronic pain.

Reparris is developing a first-in-class SRC kinase recruitment inhibitor (SRI) technology that prevents cytokine receptor recruitment and SRC kinase activation. Unlike existing SRC kinase inhibitors that bind to the catalytic ATP-binding site, the SRI technology binds to an allosteric site, reducing potential side effects while preventing protease activity, cell migration, and systemic inflammation in joint cells and other tissues. In vivo studies in a collagen-induced arthritis model demonstrated the compound exhibited anti-arthritic and analgesic effects and reduced systemic inflammation. Phase I work will evaluate dose-dependent efficacy and tolerability of SRI-15932 and backup candidate SRI-15932N in a rat joint injury model of osteoarthritis following systemic administration.

Work is performed in Lancaster, California. The performance period runs through February 28, 2027.

Abstract

Osteoarthritis (OA) is a degenerative joint condition that severely impacts mobility and quality of life for millions worldwide. Currently, there are no disease-modifying agents available on the market for the treatment of OA. Addressing the underlying causes of OA is critical for preventing disease progression, rather than merely treating the symptoms. To this end, we have developed a novel class of SRC kinase recruitment inhibitors (sris) that prevent cytokine receptor recruitment and subsequent activation of SRC kinases. This technology represents a first-in-class approach, as no SRC-targeting drug for OA currently exists. The uniqueness of our technology relative to other SRC kinase inhibitors on the market is that unlike other commercially available SRC kinase inhibitors that bind to the catalytic ATP-binding site within the SRC molecule, SRI technology, in contrast, does not inhibit the catalytic activity of SRC as IT binds to the molecule's allosteric site, which mitigates potential side effects. Preliminary studies: our in vitro and in vivo studies have demonstrated that inhibition of SRC by the SRI technology prevents protease activity, cell migration and systemic inflammation in the joint cells and multiple other tissues. Importantly, the compound showed strong anti-arthritic and analgesic effect and reduced levels of systemic inflammation after administration in collagen-induced arthritis model in mice. Based on our findings and published literature, we hypothesize that inhibition of SRC signaling will attenuate chronic inflammation in the injured joint resulting in inhibition of OA progression. Phase i aim 1. Evaluate the dose-dependent efficacy and tolerability of SRI-15932 and backup candidate, SRI-15932N, in a RAT joint injury model of OA following systemic administration of the therapeutic agent. Phase II aim 1. Create a development plan (DP) and conduct a pre- IND meeting with the FDA. Phase II aim 2. Determine systemic (plasma) and local (joint) pharmacokinetics (PK) of the lead SRI candidate in canines following oral administration and conduct a preliminary safety assessment. Phase II aim 3. Evaluate the preliminary efficacy of the lead candidate in client-owned aged companion dogs with naturally occurring multi-joint OA and associated musculoskeletal (MSK) pain. Expected outcome: upon successful completion of these aims and demonstration of proof-of-concept, the lead molecule will be utilized for a pivotal large animal study focusing on disease modification. If efficacious, this candidate will be nominated for IND-enabling studies and eventually lead to phase i human clinical trials in patients with OA and OA-associated pain. The SRI technology will be commercialized as a first-in-class oral therapeutic for the treatment of OA.