Shattuck Labs (STTK) Corporate presentation summary

Overview and pipeline

• Developing potentially first-in-class DR3-blocking monoclonal and bispecific antibodies for inflammatory and immune-mediated diseases.

• SL-325 is the lead program; RECEPTIVE-CD1 Phase 2b in Crohn’s disease is ongoing, and RECEPTIVE-HS1 Phase 2b in hidradenitis suppurativa was expected to start in 4Q 2026.

• SL-846 is a half-life-extended DR3 × IL-23 receptor bispecific; SL-425 is a half-life-extended DR3 antibody, with additional preclinical bispecifics in development.

DR3-targeting rationale

• DR3 is described as constitutively expressed in inflamed and adjacent tissue, while TL1A expression is transient; receptor blockade may provide more complete, durable inhibition of the TL1A/DR3 pathway.

• Targeting DR3 rather than soluble TL1A is designed to avoid circulating immune-complex formation; SL-325’s 3.7% Phase 1 ADA rate compares with reported 48–82% rates for anti-TL1A antibodies in similar Phase 1 trials.

• Durable inhibition of TL1A binding to DR3 may support quarterly maintenance dosing and a subcutaneous autoinjector-compatible format.

SL-325 phase 1 results

• The completed healthy-participant Phase 1 included 72 participants across single- and multiple-ascending-dose cohorts, with doses from 0.1 to 30 mg/kg.

• SL-325 was reported as well tolerated across dose levels; no severe or serious adverse events were reported, and one participant discontinued after a mild Grade 1 infusion reaction.

• No changes in measured serum cytokines, TL1A concentrations, or assessed immune-cell proportions indicated residual DR3 agonism.

• PK increased dose-proportionally from 0.1 to 30 mg/kg; estimated half-life was 16 days, with a repeated-dose accumulation ratio of 1.64–1.75.

• A single dose achieved full DR3 occupancy at 0.1 mg/kg; blockade lasted months at doses ≥1 mg/kg, potentially enabling quarterly maintenance dosing.

• ADA were detected in 2/54 SL-325-treated participants (3.7%); titers remained low, with no reported impact on PK or receptor occupancy.