Shattuck Labs (STTK) TD Cowen 46th Annual Health Care Conference summary

Program overview and scientific rationale

• Focus on developing DR3 blocking antibodies for IBD, targeting the TL1A-DR3 axis, with SL-325 as the lead candidate and SL-425 as a half-life extended variant.

• DR3 is a more stable and specific target than TL1A, potentially offering superior efficacy and lower immunogenicity.

• Over 64% of patients develop ADA to TL1A blockers due to immune complex formation, a limitation not expected with DR3 blockers.

• SL-325 is engineered to avoid Fc gamma receptor binding and receptor-mediated endocytosis, minimizing off-target effects and residual agonism.

• Non-human primate studies showed low ADA rates (~9%) and no evidence of T cell proliferation or cytokine changes, supporting safety.

Clinical development and competitive landscape

• Phase I trial for SL-325 is nearly complete, with data expected in Q2; all single ascending dose and most multiple ascending dose cohorts are enrolled.

• Phase IIb randomized controlled trial in Crohn's disease will start in Q3, enrolling 170–180 patients, comparing high dose, low dose, and placebo.

• The trial will cover both induction and maintenance phases, leveraging recent completion of chronic tox studies.

• Dose selection for phase III is expected from the phase IIb trial; SL-425 may be advanced for lifecycle management or indication splitting.

• Bispecific antibodies targeting DR3 and another validated mechanism are in preclinical development, with details to be shared later this year.

Efficacy, immunogenicity, and future directions

• Goal is 100% blockade of TL1A signaling via DR3, aiming for higher efficacy than current TL1A blockers.

• High ADA rates in TL1A blockers correlate with up to 50% reduction in efficacy at induction; DR3 blockers are expected to avoid this issue.

• Maintenance efficacy with TL1A blockers is limited by ADA-driven drug clearance, as shown in recent clinical studies.

• SL-325 is expected to allow subcutaneous dosing every 4–8 weeks, balancing efficacy and patient convenience.

• Biomarker and receptor occupancy assays are used to confirm pathway inhibition; human data on immunogenicity and efficacy are forthcoming.