XtalPi Submits FDA Application for Novel Gut-Restricted Drug for Chronic Intestinal Pain
XtalPi has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for KQTD-126, a potential first-in-class, gut-restricted pan-TRK inhibitor for chronic intestinal pain.
Boston and Shenzhen, China – XtalPi has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for KQTD-126. The internally developed candidate is a potential first-in-class gut-restricted pan-tropomyosin receptor kinase (pan-TRK) inhibitor designed to treat chronic intestinal pain associated with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
IBS affects approximately 10%–15% of the global population, while more than 10 million people live with IBD. Chronic abdominal pain is a significant burden for IBS patients and can persist in some IBD patients even when standard therapies control inflammation. Despite available treatments, there remains an unmet need for options offering sustained pain relief suitable for long-term use.
KQTD-126 targets the TRK receptor family (TRKA, TRKB, and TRKC), which directly regulate nerve activity and pain signaling in the gut. While inhibiting these pathways can manage pain, TRK receptors also function in the central nervous system. Consequently, traditional systemic TRK inhibitors carry a risk of neurological side effects. An effective chronic pain treatment requires its activity to be confined strictly to the gastrointestinal tract.
Achieving this precise biological profile involved navigating a vast chemical space to balance target affinity and kinase selectivity with properties governing tissue distribution. XtalPi utilized its generative and predictive AI models integrated with automated chemistry robots. This closed-loop process combined computational design, automated synthesis, empirical screening, and molecular refinement, enabling iterative improvements of structural variants and the achievement of robust gut restriction while maintaining strong target activity.
According to XtalPi, preclinical studies demonstrated that KQTD-126 achieved pan-TRK inhibition at sub-nanomolar concentrations (IC₅₀ < 1 nM) and maintained high selectivity over other kinases. The candidate also showed a gut-to-blood exposure ratio exceeding 1,000:1. These findings support KQTD-126's development as a locally acting treatment intended to provide sustained pain relief with a wider therapeutic window. This marks the first candidate from XtalPi's proprietary pipeline to reach the IND submission stage since the portfolio was unveiled in the company's recent interim results.