Title : REC-3964, a first-in-class molecule for the prevention of recurrent clostridioides difficile infection
Abstract:
REC-3964 is an oral, novel, diazepinedione-class chemical entity identified from Recursion’s high-content phenotypic imaging platform. REC-3964 inhibits toxins associated with Clostridioides difficile infection (CDI).
In a disease-relevant hamster model of acute CDI, REC-3964 extended survival in a dose-dependent manner. In this same model, REC-3964 significantly extended survival compared to bezlotoxumab. Monotherapy was safe and well tolerated when administered as single doses up to 1200 mg and multiple doses up to 900 mg in a healthy volunteer, single- and multiple-ascending dose study (n=90). Exposures (AUC) increased approximately dose-proportionally across dose ranges tested, and half-life ranged from approximately 7–10 hours. All treatment-emergent adverse events (TEAEs) were mild in severity with no serious adverse events, deaths, or TEAEs leading to discontinuation. No clinically relevant effects on vital signs, ECG parameters (including QTcF), or other laboratory parameters were observed in the study.
Planned study REC-3964-201 will evaluate recurrent CDI (rCDI) reduction with REC-3964 after initial clinical resolution. Based on preclinical data indiacating a dose-dependent treatment effect, two doses of REC-3964 are being explored.
Overall, these data demonstrate that REC-3964 is a safe and well-tolerated, orally bioavailable, small molecule Clostridioides difficile toxin inhibitor with potential to prevent rCDI in high-risk patients.
