Shattuck Labs Updates on SL-325, a Novel DR3 Antagonist Targeting TL1A/DR3 Pathway

Shattuck Labs, Inc., a biotechnology company specializing in developing novel therapeutics targeting tumor necrosis factor (TNF) superfamily receptors, has announced a significant strategic shift. The company has decided to discontinue its clinical program for SL-172154 and will instead prioritize the development of SL-325, a first-in-class DR3 antagonist antibody intended for the treatment of inflammatory bowel disease (IBD). This decision comes after interim clinical data for SL-172154 in combination with azacitidine for TP53 mutant acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) showed only modest improvements in median overall survival compared to azacitidine monotherapy.

SL-172154's development has been halted due to its inability to demonstrate a significant survival benefit. CEO Taylor Schreiber expressed disappointment, stating, "We are disappointed that the promising complete remission rates did not translate to meaningful improvements in median overall survival for TP53m AML and HR-MDS patients treated with SL-172154 in combination with azacitidine." Schreiber acknowledged the efforts of the clinical team and the patients who participated in the trials and emphasized the need to move on to opportunities with a higher likelihood of success.

The company is now shifting its focus to SL-325, a DR3 antagonist antibody designed to block the TL1A/DR3 signaling pathway more effectively. Schreiber believes this approach will prove more potent than current methods. This strategic shift will involve a realignment within the organization, including a roughly 40% reduction in workforce, to optimize resource allocation and position Shattuck for long-term success.

Top-line results from the Phase 1B clinical trial of SL-172154 revealed that in HR-MDS, the current median overall survival (OS) is 15.6 months, compared to benchmark data of 9-12 months for patients treated with azacitidine alone. In TP53m AML, the median OS is 10.5 months, compared to benchmark data of 5-8 months. Despite these modest improvements, SL-172154 did not show a definitive OS benefit necessary for further large-scale, randomized studies.

Additionally, Shattuck and Ono Pharmaceutical Co., Ltd. have mutually agreed to terminate their Collaboration and License Agreement. This agreement, which was focused on preclinical development of certain compounds, will no longer require Shattuck to meet any remaining performance obligations, nor will the company receive any future payments from Ono.

SL-325, Shattuck's new lead candidate, is a potentially first-in-class DR3 antagonist antibody aimed at treating IBD and other inflammatory autoimmune diseases. Preclinical studies have shown that SL-325 has high affinity binding and superior efficacy over TL1A antibodies. The company plans to file an Investigational New Drug (IND) application for SL-325 in the third quarter of 2025.

Financially, as of June 30, 2024, Shattuck reported cash and cash equivalents and investments totaling $105.3 million. The restructuring plan, following the discontinuation of SL-172154, is expected to extend the company's cash runway into 2027, allowing it to fund planned operations, including the Phase 1 clinical trial of SL-325. This financial guidance is based on current operational plans and excludes potential additional capital or costs from new development activities.

Shattuck's strategic realignment and focus on SL-325 aim to optimize the company's resources and enhance the potential for long-term success in the development of novel therapeutics for cancer and chronic immune-related diseases.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!