On March 25, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported that new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, and SGR-4174, its SOS1 inhibitor, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, taking place April 25 – 30, 2025 in Chicago, IL (Press release, Schrodinger, MAR 25, 2025, View Source [SID1234651436]).

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The SGR-3515 presentation will include data demonstrating that an optimized, intermittent dosing schedule of SGR-3515 resulted in an improved therapeutic index in preclinical oncology models. Preclinical data also showed that SGR-3515 has a differentiated profile supporting continued development as a potential therapy for patients with advanced solid tumors. A Phase 1 clinical trial in this patient population is ongoing, and Schrödinger expects to report initial clinical data from the trial in the second half of 2025.

Data will also be presented on the development of a machine learning model that predicts the response to drug combinations between Wee1 and other drugs in a large group of cell line models in selected cancer types. Additionally, the model identified several compounds as synergistic with Wee1 in new cancer settings which may be of future interest.

The SGR-4174 presentation will include data characterizing SGR-4174 in preclinical oncology models. The SOS1 protein plays a critical role in the activation and regulation of the KRAS gene. Inhibition of SOS1 is considered a potential therapeutic combination strategy for the treatment of KRAS-driven cancers. Preclinical data suggest SGR-4174 has a differentiated profile and support its continued development as a potential therapy for patients with KRAS mutant cancers and in rare diseases arising from KRAS pathway mutations. This is the first preclinical data presentation for SGR-4174.

Details of the data presentations are as follows:

Presentation Title: Optimization of therapeutic index of SGR-3515, a first-in-class Wee1/Myt1 inhibitor through intermittent dosing for monotherapy and combination with chemotherapy in xenograft tumor models
Abstract Number: #3025
Presentation Date and Time: Monday, April 28, 2025, 2-5PM CST (3-6PM ET)
Location: Poster Section 20
Session Title: Kinase and Phosphatase Inhibitors 2

Presentation Title: Machine learning-based combination prediction for Wee1 inhibitor
Abstract Number: #3660
Presentation Date and Time: Monday, April 28, 2025, 2-5PM CST (3-6PM ET)
Location: Poster Section 45
Session Title: Artificial Intelligence and Machine Learning for Therapeutic Election and Discovery

Presentation Title: Preclinical characterization of SGR-4174, a potent and selective SOS1 inhibitor for the treatment of pan KRAS mutant cancers in combination with KRAS pathway inhibitors
Abstract Number: #4376
Presentation Date and Time: Tuesday, April 29, 2025, 9AM-12PM CST (10AM-1PM ET)
Location: Poster Section 21
Session Title: RAS Inhibitors