Summary of Shattuck Labs FY Conference Call (December 04, 2025) Company Overview - **Company**: Shattuck Labs (NasdaqGS:STTK) - **Focus**: Development of a novel mechanism targeting the TL1A axis, specifically through receptor-blocking antibodies Key Points and Arguments Target Mechanism - **TL1A**: An inflammatory ligand that signals through the DR3 receptor, with a unique characteristic of only signaling through a single receptor [2][10] - **Receptor vs. Ligand Targeting**: The company is focusing on receptor-blocking antibodies due to engineering challenges and potential safety liabilities associated with ligand-blocking antibodies [2][3] Confidence in Receptor-Blocking Approach - **Safety Concerns**: Addressed concerns about potential agonist properties of receptor-blocking antibodies, emphasizing that their lead antibody showed no evidence of receptor agonism in non-human primate studies [4][5] - **Phase 1 Study**: Currently halfway through a Phase 1 study with positive early indicators regarding safety and immunogenicity [5][17] Immunogenicity Profile - **Immunogenicity Advantages**: The receptor-blocking approach is expected to have a better immunogenicity profile compared to ligand-blocking antibodies, which often lead to the formation of anti-drug antibodies (ADAs) [6][27] - **ADA Formation**: Over 65% of patients treated with TL1A antibodies develop ADAs, which can accelerate clearance of the therapeutic antibody [8][25] Efficacy Differentiation - **Stable Target**: The receptor is consistently expressed by lymphocytes, providing a stable target compared to the ligand, which is induced in a pulsatile manner [18][20] - **Potential for Better Efficacy**: The receptor-blocking strategy may lead to more effective treatment outcomes in inflammatory diseases due to stable receptor occupancy [22][26] Development Pipeline - **Half-Life Extension and Bispecifics**: The company is actively developing half-life extended versions of their antibodies and exploring bispecific antibodies targeting DR3 [28][29] - **Clinical Studies**: Plans to conduct a healthy volunteer Phase 1 study with the half-life extended version while running a Phase 2 study in inflammatory bowel disease (IBD) with the non-half-life extended version [29] Market Context and Competition - **Competitive Landscape**: Other companies, such as Teva and Novartis, are also developing TL1A-targeting therapies, but Shattuck Labs believes their receptor-focused approach offers distinct advantages [12][30] - **Potential Collaborations**: Discussion of possible combinations with biosimilar IL-23 therapies, indicating a strategic approach to enhance treatment efficacy [32][34] Additional Important Insights - **Regulatory and Market Readiness**: The company is preparing for multiple indications and potential platform trials, indicating a proactive approach to market entry and competition [33][34] - **Focus on Safety and Efficacy**: Emphasis on the importance of demonstrating a superior safety profile and efficacy in upcoming clinical trials to differentiate from existing therapies [27][28] This summary encapsulates the critical insights from the Shattuck Labs FY Conference Call, highlighting the company's innovative approach to targeting the TL1A axis and its strategic positioning in the competitive landscape of inflammatory disease therapies.