Schrödinger (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, presented new preclinical data from its CDC7 inhibitor program in a poster session on April 10, 2021, during the 2021 American Association for Cancer Research (AACR) Annual Virtual Meeting. The data showed that Schrödinger’s picomolar CDC7 inhibitors were highly selective and inhibited tumor cell growth alone and in combination with several approved and investigational cancer treatments.
CDC7 is a protein kinase that is required for DNA replication initiation and is involved in DNA replication stress response. CDC7 is thought to be linked to cancer cells’ proliferative capacity and ability to bypass normal DNA damage responses. Targeting proteins that play important roles in DNA replication and replication stress is gaining momentum as a new therapeutic approach based on the proliferative capacity of cancer cells to bypass DNA damage responses.
“Based on our preclinical data, we believe we have identified the most potent CDC7 inhibitors reported to date, capable of inhibiting cell growth and causing programmed cell death in both blood and solid tumors, while sparing healthy cells,” said Karen Akinsanya, Ph.D, executive vice president, chief biomedical scientist and head of discovery R&D at Schrödinger. “We’re excited by the rapid progress in our internal pipeline. We look forward to selecting development candidates and moving multiple oncology programs into IND-enabling studies this year.”
Additional Details About the Data Presented at AACR
The presentation, “Discovery of novel CDC7 inhibitors that disrupt cell cycle dynamics and show anti-proliferative effects in cancer cells,” highlighted preclinical data with multiple lead molecules discovered by Schrödinger scientists. The company’s CDC7 inhibitor compounds demonstrated dose-dependent picomolar potency as measured by in vitro inhibition of CDC7 enzymatic activity. The compounds were highly selective, inducing apoptosis in cancer cells but not in normal fibroblasts. They also showed synergy with several approved and investigational cancer therapies that modulate apoptosis, DNA repair mechanisms and DNA checkpoints, including venetoclax, olaparib, ceralasertib and adavosertib. Additionally, Schrödinger’s compounds significantly inhibited tumor growth in mouse models of both acute myeloid leukemia and colorectal cancer. Taken together, these data provide further rationale for developing CDC7 inhibitors as a potential therapeutic approach, particularly in combination with existing therapies.
Schrödinger’s MALT1 and Wee1 Programs
Schrödinger is continuing to advance its MALT1 and Wee1 inhibitor programs. Targeting MALT1 is emerging as a potential therapeutic strategy to treat certain relapsed or resistant B-cell lymphomas and chronic lymphocytic leukemia. In December 2020, Schrödinger scientists presented preclinical data at the American Society of Hematology (ASH) Annual Meeting highlighting that its MALT1 inhibitors demonstrated anti-tumor activity alone and in combination with approved anti-cancer therapies in models of B-cell lymphoma.
Similar to CDC7, Wee1 targets cancer through replication stress and DNA repair mechanisms. The company has identified highly selective, potent Wee1 inhibitors with optimized drug-like properties, including no observable inactivation of CYP3A4, a key liver enzyme. Lead compounds exhibited favorable pharmacokinetic properties and strong anti-tumor activity in preclinical models.
Based on the strong data generated to date, Schrödinger is on track to move forward with IND-enabling studies for its MALT1, CDC7 and Wee1 programs. Subject to completion of the preclinical data packages, the company expects to submit up to three IND applications in 2022, with the first submission expected in the first half of next year.
Today at 10:00 a.m. ET, Schrödinger will host a webcast to review the preclinical data presented from its CDC7 program at the virtual AACR Annual Meeting. The company will also provide an overview of two other internal programs, MALT1 and Wee1, as well as highlight the role of its computational platform in accelerating the discovery of its novel molecules. The webcast will be available under "News & Events" in the investors section of Schrödinger’s website, https://ir.schrodinger.com/news-and-events/event-calendar and will be archived for approximately 7 days.
Schrödinger is transforming the way therapeutics and materials are discovered. Schrödinger has pioneered a physics-based software 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 software platform is used by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schrödinger’s multidisciplinary drug discovery team also leverages the software platform to advance collaborative programs and its own pipeline of novel therapeutics to address unmet medical needs.
Founded in 1990, Schrödinger has over 450 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit www.schrodinger.com and follow us on LinkedIn and Twitter.
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 regarding Schrödinger’s expectations about the speed and capacity of its computational platform, the clinical potential of its CDC7, MALT1 and Wee1 inhibitors, the favorable properties of the CDC7, MALT1 and Wee1 inhibitors the company has identified, the expected timing of IND-enabling studies and IND submissions, as well as the potential for the company’s inhibitor programs to be used in combination with existing therapies. Statements including words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “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 the company’s current views about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to the company and on assumptions the company has made. Actual results may differ materially from those described in these forward-looking statements and are subject to a variety of assumptions, uncertainties, risks and factors that are beyond Schrödinger’s control, including the uncertainties inherent in drug development and commercialization, such as the conduct of research activities and the timing of and the company’s ability to initiate and complete preclinical studies and clinical trials, whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials, the timing of and the company’s ability to submit and obtain approval to initiate clinical development of any development candidates, uncertainties associated with the regulatory review of clinical trials and applications for marketing approvals, the ability to retain and hire key personnel, the direct and indirect impacts of the ongoing COVID-19 pandemic on the company’s business, and other risks detailed under the caption “Risk Factors” and elsewhere in Schrödinger’s Securities and Exchange Commission filings and reports, including its Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission on March 4, 2021, as well as future filings and reports by the company. Any forward-looking statements contained in this press release speak only as of the date hereof. Except as required by law, Schrödinger undertakes 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.