PatientSeek identifies genetic markers distinguishing a4b7 integrin therapy responders in inflammatory bowel disease

C4X Discovery Holdings Limited (C4XD), a company specializing in immuno-inflammation therapeutics, has announced a significant advancement in precision medicine for inflammatory bowel disease (IBD). On 16 September 2024, C4XD revealed the identification of a genetic response signature that differentiates patients with ulcerative colitis based on their response to vedolizumab, an a4b7 integrin antibody therapy. This breakthrough was achieved using their PatientSeek platform.

Executive Chairman Clive Dix highlighted the novelty of this discovery, noting that no existing biomarker has been validated to predict responses to advanced IBD therapies effectively. This has left a substantial gap in clinical practice, where many patients do not receive the most suitable treatments. Utilizing PatientSeek, C4XD has succeeded in identifying a genetic signature that distinguishes between responders and non-responders to vedolizumab. This finding illustrates the potential of PatientSeek’s analytical capabilities, which rely solely on genetic data for patient selection.

The goal of precision medicine is to match the right therapy to the right patient at the right time in their disease progression. Initially prominent in oncology, precision medicine is now gaining traction in the immuno-inflammation field. C4XD’s PatientSeek platform employs a unique mathematical methodology to analyze datasets that include patients' genetic records and other data like electronic health records. The platform aims to produce a statistically significant predictive 'genetic response signature.' Unlike clinical and omic biomarkers, genetic signatures remain constant over time and are independent of disease progression.

C4XD analyzed an extensive dataset of patients treated with vedolizumab. The initial results have demonstrated, for the first time, that responders and non-responders can be separated based on genetic variations in the non-coding regions of DNA. This capability means that PatientSeek can pinpoint genetic response signatures, potentially leading to smaller, more cost-effective, and more successful clinical trials. These trials can better target the right patient for the right drug at the right time.

C4XD plans to leverage these predictive data in future clinical trials for their own small molecule a4b7 integrin program. They also intend to apply this precision approach to advance their growing pipeline, which includes TNFa and PAD4 programs.

C4XD is a pioneering drug discovery company that combines scientific expertise with advanced technologies to develop world-leading medicines. Their unique approach to drug discovery incorporates enhanced molecular design and patient stratification capabilities, producing small molecule drug candidates across various disease indications with a focus on immuno-inflammation. C4XD's internal portfolio spans from early-stage targets to advanced drug discovery programs. They have two commercially partnered programs with Sanofi and AstraZeneca and one clinical stage candidate acquired by Indivior.