Shattuck Labs (STTK) Piper Sandler 36th Annual Healthcare Conference summary

Program focus and scientific rationale

• Shifted focus from oncology to lead program SL325, a monoclonal antibody targeting DR3, in October 2023.

• DR3 is the sole receptor for TL1A, a key driver of inflammation in IBD, with evidence supporting DR3 as a more effective target than TL1A.

• DR3 is constitutively expressed on lymphocytes, while TL1A is transiently expressed in inflamed tissues, suggesting DR3 blockade may offer more durable inflammation control.

• Preclinical data show DR3 knockout provides greater protection from inflammation than TL1A knockout in mouse models.

• Large patient registries confirm higher DR3 expression in IBD patients compared to TL1A.

SL325 antibody characteristics and competitive landscape

• SL325 is a high-affinity antibody (1.3 pM) that blocks DR3 without affecting the decoy receptor, showing superior in vitro potency over TL1A-targeting antibodies.

• No agonist activity observed in immune cell assays, confirming its antagonist profile.

• Targeting DR3 may reduce immunogenicity compared to TL1A antibodies, which form immune complexes and have high ADA rates.

• DR3 targeting enables potential for bispecific antibody development, unlike TL1A approaches.

• GLP toxicology studies for SL325 have been completed, supporting advancement to clinical trials.

Clinical development plans

• IND submission for SL325 is planned for mid-2025.

• Initial clinical trial will enroll about 70 healthy volunteers in a single and multi-ascending dose study.

• Full enrollment expected by the first half of 2026, with interim data anticipated.

• Phase II studies in ulcerative colitis and Crohn's disease will follow the initial trial.