Shattuck Labs (STTK) investor relations material

Key scientific insights

• DR3 is a stable, broadly expressed receptor in IBD, making it a promising therapeutic target compared to the transiently expressed TL1A ligand.

• Blocking DR3 may offer superior efficacy and reduced immunogenicity versus TL1A blockade, as DR3 targeting avoids immune complex formation that drives anti-drug antibody responses.

• The DR3 blocking antibody (SL325) is designed for high affinity and lacks Fc gamma receptor binding, minimizing off-target effects and residual agonism.

• Preclinical studies confirmed SL325 does not induce T cell proliferation or cytokine release, supporting its antagonist profile.

• No other disclosed DR3 antagonist programs are known, with technical challenges limiting competition.

Clinical development and strategy

• Phase 1 trials for the DR3 antibody are ongoing, with completion expected in the first half of next year.

• Plans are in place to move directly into multiple placebo-controlled phase 2 trials, including at least one in IBD.

• Comparative efficacy and immunogenicity versus TL1A antibodies will be key endpoints in upcoming studies.

• Data from these trials are anticipated in 2026.

• Study design aims to facilitate cross-trial comparisons with existing TL1A therapies.

Market and indication landscape

• TL1A/DR3 pathway is implicated in IBD, asthma, psoriatic arthritis, psoriasis, rheumatoid arthritis, and primary biliary cirrhosis.

• DR3 targeting may be especially effective in diseases with persistent antigen exposure, such as IBD and RA, compared to relapsing-remitting diseases like asthma.

• Major pharmaceutical companies are pursuing TL1A blockade in multiple indications, but DR3 antagonism may offer differentiation.

• The antibody's broad potential across autoimmune and fibrotic diseases increases its clinical and commercial attractiveness.

• No current competitors have advanced DR3 antagonists to clinical disclosure, suggesting a first-mover advantage.