Schrödinger Reports 22% Response Rate in Early Trial for Drug-Resistant B-Cell Cancers

Schrödinger, Inc. (NASDAQ:SDGR) today announced encouraging 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 (CLL) and Waldenström macroglobulinemia (WM). These data are being presented in a poster presentation at the European Hematology Association Annual Congress.

"We are very encouraged by the initial results from our Phase 1 study in patients with relapsed/refractory B-cell malignancies. The data presented today, coupled with the differentiated preclinical and safety profiles observed in our previously completed study in healthy volunteers, further increases our conviction about the potential for SGR-1505 to be a best-in-class therapy," said Margaret Dugan, M.D., chief medical officer at Schrödinger. "Dose escalation is complete, and we look forward to discussing these results and our proposed recommended Phase 2 dose with the FDA later this year."

"Despite recent advances in the treatment of B-cell malignancies, resistance to currently available therapies eventually results in treatment failure and disease progression for many patients," said Stephen Spurgeon, M.D., Associate Professor of Medicine, Oregon Health and Science University, and an investigator for the clinical study. "We know that MALT1 plays a critical role in key signaling pathways that drive cancer cell survival and proliferation, making it a promising target for a broad range of B-cell malignancies. Although these data are from an early-phase study, they suggest SGR-1505 demonstrates on-target activity resulting in potential clinical benefit. I look forward to seeing additional data as the study progresses, including response data in patients with aggressive histologies."

"The positive data reported today represent a key milestone for Schrödinger and follow the clinical successes of programs advanced by collaboration partners and companies we have co-founded," said Karen Akinsanya, Ph.D., president, head of therapeutics R&D and chief strategy officer, partnerships at Schrödinger. "These data reinforce the power of Schrödinger's platform to enable the rapid design of differentiated molecules and the impact that our computational approach can have on a drug discovery and development program."

Major Takeaways from the Study

• As of the data cut-off date, May 13, 2025, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL/SLL, nine with diffuse large B-cell lymphoma (DLBCL), six with Waldenström macroglobulinemia (WM), and five with marginal zone lymphoma (MZL).
• Patients had a median of four (range two-nine) prior lines of therapy, with the most common being Bruton's tyrosine kinase (BTK) inhibitors (55.1%), BCL-2 inhibitors (18.4%) and BTK+BCL-2 inhibitors (18.4%).
• SGR-1505 was well-tolerated with no dose-limiting toxicities or deaths due to treatment-emergent adverse events (TEAEs). Forty three percent of patients (n=21) experienced ≥ 1 treatment-related adverse event (TRAE), with the most common (≥ 10%) being rash (12%) and fatigue (12%). Ten patients (20%) experienced treatment-emergent serious adverse events (SAEs); 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 (ORR) across all dose levels was 22% (n = 10/45). 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 (PR) with lymphocytosis (PR-L). 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.