On December 12, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported new preclinical data on its potent and selective CDC7 inhibitor, SGR-2921, in a poster session at the American Society of Hematology (ASH) (Free ASH Whitepaper) 64th Annual Meeting taking place virtually and in New Orleans, Louisiana (Press release, Schrodinger, DEC 12, 2022, View Source [SID1234625174]). The data presented demonstrate that SGR-2921 exhibits strong anti-tumor activity in vivo across multiple acute myeloid leukemia (AML) models, including cell-derived xenograft models, as a monotherapy and in combination with standard of care agents. Moreover, SGR-2921 demonstrates anti-tumor activity in AML patient-derived samples resistant to standard of care agents.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
CDC7 is a cell cycle kinase involved in DNA replication and is an important activator of replication stress and DNA damage responses. CDC7 inhibition is considered a promising therapeutic approach for the treatment of cancers, including AML. Schrödinger is advancing SGR-2921 through investigational new drug (IND)-enabling studies with plans to submit an IND application to the U.S. Food and Drug Administration in the first half of 2023 and to initiate a Phase 1 clinical trial in patients with relapsed/refractory AML in the second half of 2023.
"The strength of our preclinical data presented today underscore the power of our computational platform to overcome drug design challenges that plague the industry, in this case designing a potent CDC7 inhibitor that could potentially be combined with other DNA damage repair therapies, such as PARP and BCL-2 inhibitors," said Karen Akinsanya, Ph.D., president of R&D, therapeutics, at Schrödinger. "We are pleased that our data show that SGR-2921-mediated CDC7 inhibition represents a promising novel therapeutic strategy for treating AML, with potential utility in patients with relapsed and refractory AML, and we look forward to advancing this potential best-in-class inhibitor into the clinic."
Additional Details About the Study
The presentation (Abstract #2653), "Inhibition of CDC7 with SGR-2921 in AML models results in enhanced DNA damage and anti-leukemic activity as monotherapy and in combination with standard of care agents," highlighted preclinical data for SGR-2921, which was discovered using Schrödinger’s proprietary physics-based computational platform. This platform enabled Schrödinger to assess 79 billion compounds computationally and synthesize only 226 compounds across all series for further screening. In a panel of approximately 300 cancer cell lines, AML cell lines were the most sensitive to SGR-2921, and AML patient samples were highly sensitive to CDC7 inhibition ex vivo. In vivo, SGR-2921 showed strong anti-tumor growth activity in multiple AML xenograft models at tolerated doses. In combination with hypomethylating agents, SGR-2921 increased the level of replication stress, DNA damage and apoptosis markers in vitro. Combination of SGR-2921 with venetoclax (BCL2 inhibitor) showed synergistic anti-tumor activity both in vitro and in vivo. SGR-2921 was highly active in AML cell lines resistant to FLT3 inhibitors, hypomethylating agents and venetoclax, and in multi-agent resistant cell lines. The combination of SGR-2921 with FLT3 inhibitors partially restored sensitivity to FLT3 inhibition in FLT3 resistant AML cell lines. Together, these data suggest that SGR-2921-mediated CDC7 inhibition could be a novel treatment regimen, with potential utility in patients with relapsed and refractory AML.