Shattuck Labs reports positive Phase 1 data for Crohn’s disease candidate SL-325

Shattuck Labs (NASDAQ:STTK) announced positive top-line results from its Phase 1 clinical trial of SL-325, a novel Death Receptor 3 (DR3) blocking antibody.

The first-in-human, randomized, placebo-controlled study enrolled 72 healthy volunteers to evaluate the safety, pharmacokinetics, and pharmacodynamics of the candidate, which is being developed as a potential first-in-class treatment for inflammatory bowel disease (IBD) and other immune-mediated conditions.

The trial data highlighted a favorable safety and immunogenicity profile.

Only 3.7% of participants—two out of 54 treated—developed low-titer antidrug antibodies (ADAs), which the company noted had no impact on pharmacokinetics or receptor occupancy.

This immunogenicity profile is particularly significant in the context of the TL1A inhibitor class, where high rates of ADA formation have historically been a challenge for competing therapies.

The study demonstrated complete DR3 receptor occupancy at doses of 0.1 mg/kg and higher.

Furthermore, the drug showed durable inhibition of TL1A binding, persisting for more than 10 weeks following a single dose.

Consistent with its design as an Fc-silenced, fully human monoclonal antibody, SL-325 showed no evidence of DR3 agonism or adverse cytokine changes.

All treatment-related adverse events were reported as Grade 1, with no serious adverse events observed during the trial.

Building on these results, Shattuck Labs plans to initiate the RECEPTIVE-CD1 Phase 2b clinical trial in patients with Crohn’s disease in the third quarter of 2026.

The study is expected to enroll approximately 174 patients across the U.S., Canada, and Europe, utilizing a 12-week induction period followed by a 40-week maintenance phase to evaluate primary clinical efficacy endpoints.

Beyond SL-325, Shattuck provided an update on its pipeline, noting that its lead bispecific candidate, SL-846—designed to target both DR3 and the IL-23 receptor—is currently progressing through IND-enabling toxicology studies.

The company expects to initiate Phase 1 clinical trials for SL-846 in the first half of 2027.

Shattuck remains well-capitalized to fund these operations, with cash and cash equivalents reported at approximately $90.4 million as of March 31, 2026, providing a projected financial runway into 2029.