XtalPi Files FDA IND for KQTD-126, a Gut-Restricted pan-TRK Inhibitor for IBS and IBD Pain
核心洞察
XtalPi (搜索) has submitted an Investigational New Drug application to the U.S. FDA for KQTD-126 (搜索), a gut-restricted pan-TRK inhibitor for chronic intestinal pain (搜索) in IBS and IBD.
The candidate is described as the first gut-restricted pan-TRK inhibitor for these indications, designed to avoid the neurological side effects of systemic TRK inhibitors.
Preclinical data show sub-nanomolar pan-TRK inhibition with IC50 below 1 nM and a gut tissue-to-blood exposure ratio exceeding 1,000:1.
XtalPi (搜索) announced on Sept. 24, 2026 that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (搜索) for KQTD-126 (搜索), a potential first-in-class gut-restricted pan-tropomyosin receptor kinase (pan-TRK) inhibitor for chronic intestinal pain (搜索) associated with irritable bowel syndrome (搜索) (IBS) and inflammatory bowel disease (搜索) (IBD). The candidate was developed internally and represents the first IND submission from the company's proprietary pipeline, which was unveiled in its recent interim results.
Targeting TRK Signaling While Staying in the Gut
KQTD-126 (搜索) targets the TRK family of receptors, TRKA (搜索), TRKB (搜索) and TRKC (搜索), which directly regulate nerve activity and pain-signal amplification in the gut. Inhibiting these pathways can manage visceral pain, but TRK receptors also operate throughout the central nervous system, so traditional systemic TRK inhibitors carry a high risk of neurological side effects. According to XtalPi (搜索), a viable chronic pain treatment must therefore confine its activity strictly to the gastrointestinal tract.
In preclinical studies, KQTD-126 (搜索) achieved pan-TRK inhibition at sub-nanomolar concentrations, with an IC50 below 1 nM, and maintained high selectivity over other kinases. The candidate also demonstrated a gut tissue-to-blood exposure ratio exceeding 1,000:1. XtalPi (搜索) states that these findings support development of KQTD-126 as a locally acting treatment intended to deliver sustained pain relief with a wider therapeutic window.
AI and Robotics in the Design Loop
XtalPi (搜索) reports that achieving this biological profile required navigating a vast chemical space to balance target affinity and kinase selectivity against the properties governing tissue distribution. To resolve these competing design objectives, the company used generative and predictive AI models integrated with a fleet of automated chemistry robots. This closed-loop process of computational design, automated synthesis, empirical screening and molecular refinement allowed iteration across structural variants to achieve gut restriction while preserving target activity and selectivity.
Unmet Need in Chronic Abdominal Pain
IBS affects approximately 10% to 15% of the global population, and more than 10 million people live with IBD. Chronic abdominal pain is a major burden for patients with IBS and can persist in some patients with IBD even when standard therapies control their underlying inflammation. Despite available treatments, XtalPi (搜索) notes that additional options providing sustained pain relief and suitable for long-term use remain an unmet clinical need. According to BCC Research, the global IBS and IBD therapeutics market is projected to reach US$52.6 billion by 2030.
Pipeline Context
KQTD-126 (搜索) is the first program in XtalPi (搜索)'s proprietary pipeline to reach an IND submission since the portfolio was disclosed in the company's interim results. XtalPi describes itself as a global scientific utility platform built on a shared foundation of quantum physics, AI and robotics, with discovery capabilities spanning small molecules, antibodies, peptides, siRNA therapeutics and molecular glues. The company, founded in 2015 by three physicists from the Massachusetts Institute of Technology, integrates first-principles calculations, AI algorithms, high-performance cloud computing and standardized automation systems to provide R&D solutions across pharmaceutical, materials science, agricultural technology, energy, new chemicals and cosmetics industries.