Shattuck Labs has hammered another nail into the coffin of CD47. After seeing a “modest” effect on survival in blood cancer, the biotech axed its candidate, pivoted to a preclinical program and gave 40% of its employees pink slips.
The dropped molecule is a dual-sided fusion protein with three functional domains, a design intended to enable macrophages to eat cancer cells while activating antigen-presenting cells and avoiding anemia. As other companies dropped out of the space, Shattuck’s SL-172154 became the leading CD47 candidate in acute myeloid leukemia (AML).
However, hopes that the company could buck the trend in CD47 have faded throughout 2024. Shattuck’s share price fell after the publication of interim data in May and June, falling from above $10 to below $4. Now, a third look at the data has persuaded Shattuck to drop the program.
The biotech said it saw “only modest improvement in median overall survival compared to azacitidine monotherapy benchmarks.” In AML, the current median overall survival (OS) in patients who received SL-172154 and the chemotherapy drug azacitidine is 10.5 months and, at best, could reach 11.7 months. The benchmark for TP53m AML patients treated with azacitidine alone is five to eight months.
In TP53m higher-risk myelodysplastic syndromes, Shattuck reported a median OS of 10.6 months that won’t improve beyond 13.1 months in subsequent data cuts. The biotech’s benchmark in that setting is 9 to 12 months. The data prompted the biotech to move on to “opportunities with a higher probability of success,” Shattuck CEO Taylor Schreiber, M.D., Ph.D., said in a statement.
Shattuck is now focused on SL-325, a DR3 antagonist antibody. The biotech has identified DR3 blockade as a way to treat inflammatory bowel disease. Shattuck is aiming to file to test the antibody in humans in the third quarter of 2025. SL-325 acts on the same pathway as TL1A, the target of a molecule Roche bought for $7.1 billion. Shattuck believes targeting DR3 rather than TL1A will improve potency.
The company will need fewer employees to execute its revised strategy. Having ended last year with 75 full-time employees across two sites in Texas and North Carolina, Shattuck is now laying off 40% of its staffers. The change will result in restructuring charges of around $1.5 million but ultimately cut costs, extending the biotech’s cash runway into 2027 and beyond the delivery of phase 1 data on SL-325.
Shattuck shared details of the changes alongside news of the end of its deal with Ono Pharmaceutical. Ono paid $2 million upfront in February to collaborate on bifunctional fusion proteins directed toward a pair of targets for the potential treatment of autoimmune and inflammatory diseases. The Japanese drug developer put up $3.4 million to fund the first six months of research.
Rather than continue the collaboration, Shattuck and Ono have mutually agreed to terminate the license deal. The termination deprives Shattuck of the chance to pocket more payments from Ono, including up to $7 million tied to research milestones, but also frees the biotech from performance obligations.
Shares in Shattuck fell 51% to $1.72 in premarket trading.