New preclinical data on PRMT5-MTA inhibitor program will also be presented

Schr�dinger (Nasdaq: SDGR) today announced new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, during a poster session at the 36th EORTC-NCI-AACR Symposium (ENA 2024). The data demonstrate that in preclinical models, treatment with SGR-3515 results in synergistic anti-tumor activity that leads to deeper and more durable responses compared to inhibitors that target only Wee1 or Myt1. The preclinical data also show that SGR-3515 has a favorable pharmacological profile and dosing schedule that supports evaluating intermittent dosing in patients.

Wee1 and Myt1 kinases regulate the cell cycle and DNA damage response, allowing time for DNA repair before cell division takes place. Concurrent loss of function or inhibition of Wee1 and Myt1 confers selective vulnerability in cancer cells, a mechanism referred to as synthetic lethality, which has become an emerging therapeutic strategy for a range of cancers. A Phase 1 dose-escalation study of SGR-3515 in patients with advanced solid tumors is ongoing in the U.S. and Canada, and initial data from the clinical study is expected in the second half of 2025.

Schr�dinger will also present preclinical data from its PRMT5-MTA program during a poster session on October 25. Schr�dinger scientists have identified a novel series of selective, potent PRMT5-MTA inhibitors and are optimizing lead compounds for use in peripheral and brain tumors.

“We are pleased to share these encouraging preclinical data on SGR-3515, a potential best-in-class treatment for patients with a broad range of solid tumors, including uterine and ovarian cancers, two patient populations with high unmet need,” stated Karen Akinsanya, Ph.D., president of R&D therapeutics at Schr�dinger. “We also look forward to presenting preclinical data on the discovery of a novel series of compounds for our PRMT5-MTA inhibitor program. These programs highlight how we are deploying our computational platform at scale to discover highly optimized molecules to address diseases with significant medical need, and we believe the future of our therapeutics portfolio is very promising.”

SGR-3515 Data at ENA 2024 The presentation (Abstract # 147), “Discovery of SGR-3515, a first-in-class Wee1/Myt1 inhibitor with differentiated pharmacological properties in xenograft tumor models,” includes preclinical data demonstrating superior anti-tumor activity of SGR-3515 compared to inhibitors of Wee1 or Myt1 alone due to strong target engagement of both Wee1 and Myt1. The data show that SGR-3515 is a more potent co-inhibitor of both Wee1 and Myt1 than previously disclosed inhibitors of either target. These data are consistent with prior preclinical observations demonstrating that SGR-3515 has a unique and differentiated pharmacological profile that supports evaluating an intermittent dosing schedule of three days on and 11 days off, as well as five days on and nine days off, which maintained anti-tumor activity while allowing recovery from any mechanism-based hematological toxicity in preclinical models.

The preclinical data also demonstrate superior kinase selectivity and in vitro cell potency of SGR-3515 across a broad cell line panel compared to other known Wee1 and Myt1 inhibitors. These new data suggest that SGR-3515 is significantly more selective than existing compounds with low potential for drug-drug interaction.

PRMT5-MTA Data at ENA 2024 Additionally, Schr�dinger will present new preclinical data on its PRMT5-MTA inhibitor program at a poster session during the meeting on October 25 from 9:00 a.m. - 3:00 p.m. CEST. The presentation (Abstract # 372), “Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology,” will include preclinical data on the discovery of highly selective PRMT5-MTA inhibitors. The poster will describe how Schr�dinger’s virtual screening platform facilitated the identification of structurally distinct chemical matter with a high degree of MTA-synergy for compounds within a novel chemical series in vitro and in cellular contexts. Schr�dinger has identified a novel series of selective, potent PRMT5-MTA inhibitors that did not show major off-target liabilities such as hERG inhibition in preclinical studies and may be suitable for use in combinations across tumor types.

About Schr�dinger Schr�dinger is transforming the way therapeutics and materials are discovered. Schr�dinger has pioneered a physics-based computational platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The computational platform is licensed by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schr�dinger’s multidisciplinary drug discovery team also leverages the software platform to advance a portfolio of collaborative and proprietary programs to address unmet medical needs.

Founded in 1990, Schr�dinger has approximately 850 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit www.schrodinger.com, follow us on LinkedIn, or visit our blog, Extrapolations.com.

Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including but not limited to those statements regarding the potential advantages of our computational platform, the potential of Wee1/Myt1 and PRMT5-MTA inhibition for the treatment of cancers, the therapeutic potential and characteristics of SGR-3515 and the PRMT5-MTA inhibitors we have identified, the expected timing and design of our Phase 1 clinical trial of SGR-3515, including the plan to evaluate SGR-3515 with an intermittent dosing schedule, and the future potential of our therapeutics portfolio. Statements including words such as “aim,” "anticipate," "believe," "contemplate," "continue," "could," "estimate," "expect," “goal,” "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," "would" and statements in the future tense are forward-looking statements. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Actual results may differ materially from those described in the forward-looking statements and are subject to a variety of assumptions, uncertainties, risks and factors that are beyond our control, including the uncertainties inherent in drug development, such as the conduct of research activities and the timing of and our ability to initiate and complete preclinical studies and clinical trials, whether results from preclinical studies and early clinical trials will be predictive of results of later preclinical studies and clinical trials, uncertainties associated with the regulatory review of clinical trials and applications for marketing approvals, the ability to retain and hire key personnel and other risks detailed under the caption "Risk Factors" and elsewhere in our Securities and Exchange Commission filings and reports, including our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on July 31, 2024, as well as future filings and reports by us. Any forward-looking statements contained in this press release speak only as of the date hereof. Except as required by law, we undertake no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events, changes in expectations or otherwise.

Matthew Luchini (Investors) matthew.luchini@schrodinger.com 917-719-0636 Allie Nicodemo (Media) allie.nicodemo@schrodinger.com 617-356-2325

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