Shattuck Labs (STTK) Study Update summary

Mechanism of action and differentiation

• SL-172154 is a bifunctional fusion protein targeting CD47 and activating CD40, designed to avoid anemia and cytopenias seen with prior CD47 inhibitors.

• The CD40 ligand domain uniquely links innate and adaptive immunity, potentially enhancing anti-tumor response and durability.

• Dual mechanism may contribute to higher response rates compared to other CD47-targeted agents, with no evidence of Fc-mediated cytopenias.

• Emerging data suggest a correlation between CD40-mediated cytokine induction and clinical remission.

Study design and patient population

• Phase 1A/1B trial evaluated SL-172154 plus azacitidine in frontline higher-risk MDS and TP53 mutant AML, with dose escalation identifying 3 mg/kg as the recommended dose.

• The AML cohort included 21 patients, 91% with complex cytogenetics and 67% with secondary or therapy-related AML.

• The MDS cohort included 24 patients, with a high proportion of TP53 mutations and complex karyotypes, indicating poor prognosis.

• Patient populations had high rates of transfusion dependence and poor prognosis.

• Ongoing and planned randomized expansion cohorts will further evaluate efficacy and safety in HR-MDS and AML.

Safety and tolerability

• Infusion-related reactions were the most common adverse event, mitigated by dexamethasone pre-medication.

• No evidence of hemolytic anemia or need for hyper-transfusion was observed; hemoglobin levels remained stable post-infusion.

• Grade 3/4 adverse events included neutropenia, thrombocytopenia, and febrile neutropenia; deaths mainly attributed to underlying disease and comorbidities.

• No grade 3 or higher infusion reactions occurred with dexamethasone premedication.

• Several patients achieved transfusion independence.