Shattuck Labs (STTK) Wells Fargo 21st Annual Healthcare Conference summary

Strategic focus and scientific rationale

• Current pipeline centers on DR3 blockade, offering advantages over TL1A targeting due to greater target stability and reduced immunogenicity.

• DR3 is a stable receptor expressed on lymphocytes and endothelial cells, making it a more consistent therapeutic target than the transiently expressed TL1A.

• Pharmacodynamic assays for DR3 blockade directly measure TL1A binding inhibition, providing clearer efficacy signals.

• Developing a DR3-blocking antibody is technically challenging due to the need to avoid residual agonism, which could worsen inflammation.

• SL-325, the lead DR3 antibody, demonstrated no agonist activity in preclinical and human studies.

Clinical differentiation and efficacy potential

• TL1A class shows higher induction remission rates than IL-23s, but lacks improvement from induction to maintenance due to anti-drug antibodies (ADA).

• Data from the ARTEMIS-UC trial suggest that high-dose maintenance can double remission rates, but ADA limits this benefit.

• SL-325's low ADA rate (3.7%) is attributed to the absence of immune complex formation, unlike TL1A antibodies.

• Quarterly dosing is projected to be feasible with SL-325 due to durable DR3 occupancy, as shown in phase I.

• Phase II RECEPTIVE-CD1 trial in Crohn's disease is underway, with induction data expected in H1 2028 and maintenance data later that year.

Market positioning and future plans

• DR3 blockade is expected to outperform TL1A and potentially IL-23s, especially in maintenance efficacy due to lower immunogenicity.

• The company is developing a bispecific antibody (SL-846) targeting DR3 and IL-23R, with clinical entry planned for early next year.

• Combination therapies are anticipated to be the future standard in IBD, with DR3 blockade positioned as a desirable backbone.

• The pipeline may expand into other indications such as hidradenitis suppurativa and primary biliary cirrhosis, leveraging the anti-fibrotic potential of TL1A/DR3 inhibition.

• Cash runway extends into 2029, supporting ongoing phase II and planned phase I trials, with flexibility for additional indications.