On April 12, 2021 Schrödinger (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that 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) (Free AACR Whitepaper) Annual Virtual Meeting (Press release, Schrodinger, APR 12, 2021, View Source [SID1234577928]). 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.

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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 (Free AACR Whitepaper)

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) (Free ASH Whitepaper) 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.

Webcast Information

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 (Free AACR Whitepaper) 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, View Source and will be archived for approximately 7 days.