Shattuck Labs (STTK) investor relations material

Strategic focus and differentiation

• Exclusively targets the DR3 receptor, offering potential efficacy advantages over TL1A antibodies due to DR3's stable expression and lower immunogenicity.

• DR3 blockade is expected to outperform TL1A antibodies in all indications where TL1A is effective, with a more durable pharmacodynamic effect.

• Phase I data for SL-325 showed pure DR3 antagonism, durable receptor occupancy at low doses, and a low ADA rate of 3.7%.

• Subcutaneous and IV formulations are being developed, with ongoing studies to compare bioavailability and optimize dosing.

• Bispecific antibody SL-846 targets both DR3 and IL-23R, aiming for enhanced efficacy in diseases where both pathways are relevant.

Clinical development and trial design

• Initial focus is on Crohn's disease due to stronger genetic linkage and a less crowded clinical landscape compared to ulcerative colitis.

• Phase II trial uses a three-arm, randomized, blinded design with treat-through from induction to maintenance, enabling robust ITT analysis.

• Dosing strategy includes high, middle, and low doses to ensure full DR3 occupancy and inform future phase III schedules.

• Subcutaneous formulation is feasible for all doses, with potential use of on-body devices for higher doses.

• ADA impact is expected to be more pronounced in maintenance, with differentiation from TL1A antibodies anticipated over time.

Pipeline expansion and future indications

• Plans to pursue hidradenitis suppurativa (HS) as a priority non-IBD indication, aiming to be among the lead developers.

• Psoriatic arthritis is considered a high-probability target for both DR3 and bispecific approaches.

• Chronic tox studies in NHPs for the bispecific SL-846 show no unexpected agonism and manageable ADA rates.

• Additional bispecifics are in development, with future advancement dependent on immunogenicity data from ongoing studies.

• Further updates on non-IBD indications and bispecific pipeline are expected soon.