Schrodinger announces initial clinical data from SGR-1505 study

Schrodinger (SDGR) announced initial clinical data from its ongoing Phase 1, open-label, dose-escalation study of SGR-1505 in patients with relapsed/refractory B-cell malignancies. SGR-1505 was observed to be safe, well tolerated, and clinically active, with responses observed in multiple histologies, including in patients with chronic lymphocytic leukemia and Waldenstrom macroglobulinemia. These data are being presented in a poster presentation at the European Hematology Association Annual Congress. As of the data cut-off date, May 13, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL/SLL, nine with diffuse large B-cell lymphoma, six with Waldenstrom macroglobulinemia and five with marginal zone lymphoma. Patients had a median of four prior lines of therapy, with the most common being Bruton’s tyrosine kinase inhibitors, BCL-2 inhibitors and BTK+BCL-2 inhibitors. SGR-1505 was well-tolerated with no dose-limiting toxicities or deaths due to treatment-emergent adverse events. Forty three percent of patients experienced 1 treatment-related adverse event, with the most common being rash and fatigue. Ten patients experienced treatment-emergent serious adverse events; one was treatment-related. All blood bilirubin increased TEAEs were asymptomatic, reported in patients with UGT1A1 polymorphisms and none were Grade 4. Inhibition of IL-2 is a pharmacodynamic biomarker for target engagement and an exploratory endpoint in the study. Preliminary data indicated that SGR-1505 inhibits T-cell derived IL-2 upon ex vivo stimulation achieving the PD target of ~90% inhibition in the majority of PD-evaluable participants treated at 150 mg QD and all Q12H doses at steady state. Preliminary efficacy data indicated SGR-1505 was clinically active as a monotherapy in a number of relapsed/refractory B-cell malignancies. Of the 49 participants, 45 patients had at least one follow-up disease assessment or disease progression and were evaluable for preliminary efficacy. The overall response rate across all dose levels was 22%. Thirteen of 49 patients had been on treatment for 120 days. Among patients with indolent disease, 3/17 CLL/SLL, 5/5 WM, and 1/5 MZL patients responded. The responses of the three CLL responders were independently reviewed and confirmed, and two had a partial response with lymphocytosis. Two of three CLL patients with partial responses were double-exposed to BTK and BCL-2 inhibitors, and all WM patients were exposed to BTK inhibitors. The study recently began enrolling patients with aggressive lymphomas into the 300 mg QD and 100 mg Q12H cohorts. A PR was reported in one of four ABC-DLBCL patients.