SL-325

June 8, 2026: Shattuck Labs, Inc. (NASDAQ: STTK) reported Phase 1 first-in-human data for SL-325, its DR3-blocking antibody targeting the DR3/TL1A pathway. The randomized, placebo-controlled trial in healthy volunteers (72 participants; single-ascending doses 0.1–30 mg/kg and multiple-ascending doses 1–10 mg/kg) showed SL-325 was well tolerated with no serious TEAEs/SAEs; all treatment-related AEs were Grade 1 (12 participants). Antidrug antibodies were detected in 3.7% (2/54) of SL-325 recipients, low titer (≤16), with no observed impact on PK or receptor occupancy. Complete DR3 occupancy (blockade of TL1A binding) was observed at doses ≥0.1 mg/kg; inhibition was durable for >10 weeks, and PK modeling suggests >3 months durability at >1 mg/kg. No evidence of DR3 agonism, lymphocyte proliferation, cytokine changes, or TL1A increases was observed. A subcutaneous formulation has been developed, with potential for quarterly dosing.

Upcoming catalysts: RECEPTIVE-CD1 Phase 2b in moderate-to-severe Crohn’s disease is expected to start in Q3 2026 (primary endpoint: endoscopic response at Week 12; data expected 1H 2028). Bispecific SL-846 (DR3xIL-23R) is in IND-enabling GLP tox; safety/immunogenicity data expected 2H 2026, IND submission targeted 1H 2027, and Phase 1 start expected 1H 2027.