Shattuck Labs Prioritizes SL-325, a DR3 Antagonist, for Inflammatory Bowel Disease
Key Insights
Shattuck Labs discontinues the clinical program for SL-172154 after modest survival improvements in TP53m AML and HR-MDS patients compared to azacitidine monotherapy.
The company will now focus on SL-325, a first-in-class DR3 (search) antagonist antibody, targeting the TL1A (search)/DR3 signaling pathway for inflammatory bowel disease (search) (IBD) treatment.
An Investigational New Drug (IND) application for SL-325 is expected to be filed in Q3 2025, with preclinical studies showing high affinity binding and superior efficacy over TL1A (search) antibodies.
Shattuck Labs, Inc. is shifting its strategic focus to SL-325, a first-in-class Death Receptor 3 (DR3 (search)) antagonist antibody, after discontinuing the development of SL-172154 due to underwhelming clinical trial results. The company plans to initiate clinical development of SL-325 in patients with inflammatory bowel disease (search) (IBD), where blocking the TL1A (search)/DR3 pathway has shown promising monotherapy efficacy.
Discontinuation of SL-172154
Interim Phase 1B clinical data for SL-172154, in combination with azacitidine, in patients with TP53 mutant (TP53m) acute myeloid leukemia (search) (AML) and higher-risk myelodysplastic syndromes (search) (HR-MDS), revealed only modest improvements in median overall survival (OS) compared to azacitidine alone. In HR-MDS patients, the median OS was 15.6 months, compared to a benchmark of 9-12 months with azacitidine alone. Similarly, in TP53m AML patients, the median OS was 10.5 months, versus a benchmark of 5-8 months with azacitidine alone. Given these results, Shattuck has decided to discontinue further development of SL-172154.
Focus on SL-325
SL-325 is designed to achieve a more complete blockade of the TL1A (search)/DR3 (search) signaling pathway. Preclinical studies have demonstrated that SL-325 exhibits high affinity binding and superior efficacy compared to TL1A antibodies. Shattuck anticipates filing an Investigational New Drug (IND) application for SL-325 in the third quarter of 2025.
Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck, stated, "We are announcing a strategic shift to focus on SL-325, a DR3 (search) antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A (search)/DR3 signaling pathway... We believe SL-325 could be a first-in-class DR3 receptor blocking antibody, and that this approach will prove more potent than blocking TL1A, for many of the same reasons that blocking PD-1 has proven more potent than blocking PD-L1."
Corporate Restructuring and Financial Outlook
Shattuck Labs is implementing a restructuring plan, including an approximate 40% reduction in workforce, to prioritize the development of SL-325. As of June 30, 2024, the company's cash and cash equivalents and investments totaled $105.3 million. The restructuring is expected to extend the company's cash runway into 2027, beyond the anticipated results from the planned Phase 1 clinical trial of SL-325.
Termination of Collaboration with Ono Pharmaceutical
Shattuck and Ono Pharmaceutical Co., Ltd. mutually agreed to terminate their Collaboration and License Agreement, effective September 30, 2024. The collaboration focused on the preclinical development of certain compounds.