Shattuck Labs (NasdaqGS:STTK) 2025 Conference Transcript

Summary of Shattuck Labs Conference Call Company Overview - Company: Shattuck Labs (NasdaqGS:STTK) - Focus: Development of the first in-class death receptor three (DR3) blocking antibody for inflammatory bowel disease (IBD) targeting TL1A [1][2] Core Industry Insights - Target Mechanism: DR3 is the sole signaling receptor for TL1A, a well-known target in IBD [2] - Efficacy Comparison: Targeting DR3 may provide superior efficacy compared to existing TL1A blocking antibodies due to differences in expression patterns and stability [3][10] Key Points on DR3 vs. TL1A - Expression Levels: - TL1A is expressed in about 8-10% of cells in actively inflamed tissue of Crohn's disease patients, while DR3 is expressed in 18-20% of those cells [5][6] - DR3 shows broader and more stable expression, making it a more reliable target [6][10] - Immunogenicity: - TL1A blocking antibodies have shown high rates of anti-drug antibody formation (over 65% in some cases), leading to accelerated clearance and loss of response [18][19] - DR3 does not generate immune complexes, potentially reducing immunogenicity [20] Development of SL-325 - Antibody Characteristics: SL-325 is a high-affinity human DR3 blocking antibody with no Fc gamma receptor binding activity, minimizing the risk of residual agonism [22][24] - Clinical Development Timeline: Phase one study is expected to complete in the first half of next year, with plans to move into multiple placebo-controlled phase two trials [31] Potential Indications and Market Opportunities - Indications for Development: - Initial focus on IBD (Crohn's disease and ulcerative colitis) with potential expansion into other autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and asthma [32][34] - The presence of specific single nucleotide polymorphisms (SNPs) in TL1A may drive pathology in various diseases [33] - Market Need: There is a high unmet medical need in diseases associated with TL1A signaling, making the development of DR3 blocking antibodies potentially lucrative [35] Competitive Landscape - Current Competitors: No disclosed programs for DR3 antagonists are known, although other companies have attempted development but faced challenges with agonist activity [29][30] Conclusion - Shattuck Labs is positioned to advance its DR3 blocking antibody, SL-325, with a focus on addressing the limitations of existing TL1A therapies and exploring a range of autoimmune diseases where there is significant unmet medical need [39]