On December 10, 2023 Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported new preclinical data on SGR-1505, its investigational MALT1 inhibitor, and SGR-2921, its investigational CDC7 inhibitor, in a poster session at the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting taking place virtually and in San Diego, California (Press release, Schrodinger, DEC 10, 2023, View Source [SID1234638395]). The preclinical data reported show that both SGR-1505 and SGR-2921 have multiple favorable attributes and the potential for combination activity with standard-of-care agents.

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Schrödinger also reported preliminary pharmacodynamic data from the Phase 1 study of SGR-1505 in healthy subjects, which showed that SGR-1505 inhibited cytokine release in human whole blood and demonstrated evidence of MALT1 inhibition in humans. The company will report additional data from the healthy subject study at its Pipeline Day on December 14, 2023.

"The pharmacological data for SGR-1505 and SGR-2921 demonstrate that our development candidates have favorable, differentiated profiles with best-in-class potential," stated Karen Akinsanya, Ph.D., president of R&D therapeutics at Schrödinger. "Our progress within these programs further validates our computational approach to designing therapies with the potential to address the limitations of current treatments. SGR-1505 and SGR-2921 are now being evaluated in Phase 1 clinical studies, and we look forward to seeing these programs advance."

A Phase 1 dose-escalation study of SGR-1505 in relapsed or refractory B-cell malignancy patients is ongoing in the U.S. and Europe. Additionally, a Phase 1 clinical study of SGR-2921 was recently initiated in patients with acute myeloid leukemia or myelodysplastic syndrome. Both studies are designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and determine the recommended dose for further development.

SGR-1505 Data at ASH (Free ASH Whitepaper)

The presentation (Abstract # 2997), "SGR-1505 is a Potent MALT1 Protease Inhibitor with a Potential Best-in-Class Profile," includes preclinical data demonstrating the potency of SGR-1505 and the potential for combination activity with standard of care agents. Preclinical data showed that SGR-1505 is more potent than JNJ-6633, which has previously provided clinical validation for MALT1 inhibition as a potential therapeutic strategy for treating both chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHL). In a preclinical model of diffuse large B-cell lymphoma, SGR-1505, in combination with venetoclax, demonstrated a stronger combination impact on cell viability compared to JNJ-633 plus venetoclax. Gene expression analysis showed that SGR-1505 provides greater modulation of NF-ΚΒ and related pathway genes compared to JNJ-6633. Signaling of the NF-ΚΒ pathway is known to play a critical role in the initiation and progression of many types of cancers, particularly B cell malignancies.

Preliminary clinical biomarker data from the Phase 1 study in healthy subjects showed that SGR-1505 inhibited cytokine release in ex vivo stimulation of human whole blood. The inhibition of certain cytokines in whole blood from human subjects dosed with SGR-1505 provides pharmacodynamic evidence of MALT1 inhibition. These data are consistent with prior preclinical observations in an in vitro whole blood assay from healthy human subjects, where approximately a 50-fold lower concentration of SGR-1505 was needed to achieve 90 percent inhibition of cytokine release compared to JNJ-6633. The data support continued evaluation of SGR-1505 in the ongoing Phase 1 study in patients with advanced B-cell malignancies.

SGR-2921 Data at ASH (Free ASH Whitepaper)

The presentation (Abstract #2801), "SGR-2921, a Potent CDC7 Inhibitor, Demonstrates Significant Anti-Leukemic Responses in Patient-Derived AML Models Representing Difficult-to-Treat Disease," includes preclinical data for SGR-2921 which demonstrate the potency, breadth of activity and synergistic effects of SGR-2921 in combination with standard-of-care therapies. In vitro, SGR-2921 exhibited greater potency compared to other clinical-stage CDC7 inhibitors and showed anti-proliferative activity in AML patient-derived samples regardless of driver mutations. In vivo, SGR-2921 showed dose-dependent reduction of AML blasts in multiple AML models representing difficult-to-treat disease. SGR-2921 also showed synergistic activity in combination with decitabine in p53-mutated AML models in vivo. Together, these data support the ongoing evaluation of SGR-2921 as a potential treatment for AML, with particular utility in patients with high-risk mutations and relapsed and refractory AML.

Schrödinger Pipeline Day Webcast Information

Schrödinger will review the company’s proprietary research and development programs, including updates on SGR-1505 and SGR-2921, at its Pipeline Day taking place in-person and virtually on December 14, 2023. Pipeline Day will be a hybrid event, with a webcast and limited in-person attendance available to members of the investment community. The presentation can be accessed in the "Investors" section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event.