On December 14, 2023 Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported a detailed review of its proprietary drug discovery and development programs during its Pipeline Day today, from 10:00 a.m. – 12:30 p.m. ET (Press release, Schrodinger, DEC 14, 2023, View Source [SID1234638587]).

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"We are excited to share our first clinical data for a proprietary Schrödinger program, SGR-1505, and to outline the opportunities emerging from our broad portfolio of drug discovery programs in multiple therapeutic areas, including oncology, immunology and neurology," stated Karen Akinsanya, Ph.D., president of R&D, therapeutics at Schrödinger. "Our therapeutics team has been very productive since we started building this portfolio. With two programs in the clinic, multiple programs in late discovery and preclinical development, and our advancing collaborations, we believe the future of our therapeutics portfolio is very promising."

SGR-1505 Clinical Progress and Program Update

During Pipeline Day, Schrödinger is presenting new data showing that its novel MALT1 inhibitor, SGR-1505, was well tolerated in a Phase 1 study of 73 healthy volunteers. No drug-related serious adverse events or dose limiting toxicities were observed in the study. In the study, SGR-1505 achieved greater than 90 percent inhibition of IL-2 secretion in activated T cells, confirming target engagement and meeting the pharmacodynamic goals for the study. The data support continued evaluation of SGR-1505 in the ongoing Phase 1 study in patients with relapsed or refractory B-cell malignancies.

"The data presented from our successful healthy volunteer study demonstrate that SGR-1505 is well-tolerated with a pharmacokinetic and pharmacodynamic profile that supports continued development," stated Margaret Dugan, M.D., chief medical officer at Schrödinger. "These data add significantly to our understanding of SGR-1505 and inform our clinical development strategy in hematologic malignancies. The SGR-1505 program is progressing well, and we look forward to continued enrollment in the patient study and reporting initial data in late 2024 or 2025."

Schrödinger is also presenting preclinical data for SGR-1505 demonstrating that SGR-1505 has favorable attributes and the potential for combination activity with standard-of-care agents in B cell malignancies. These data were presented earlier this week at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Three New Programs: EGFRC797S, PRMT5-MTA and NLRP3

Schrödinger is presenting three new proprietary discovery programs at Pipeline Day, targeting EGFRC797S, PRMT5-MTA and NLRP3.

EGFR inhibitors are first-line standard of care agents for advanced non-small cell lung cancer patients with activating EGFR mutations, but relapse often occurs due to the development of resistance mutations, including EGFRC797S. Schrödinger has identified multiple EGFRC797S inhibitors and is advancing wild-type sparing, double mutant CNS-penetrant inhibitors with the potential to address brain metastases in patients whose disease progresses following first-line treatment, and to potentially achieve deeper, more durable responses through new combination regimens.

PRMT5-MTA inhibition has demonstrated clinical responses in both hematologic and solid tumors with improved safety versus PRMT5 inhibitors due to a synthetic lethal targeting of cancer cells with MTAP-deletions. Schrödinger has identified selective, potent PRMT5-MTA inhibitors with potential applications in solid tumors, brain metastases and primary CNS tumors.

NLRP3 is a validated target, and mutations in the NLRP3 gene are associated with a broad spectrum of inflammatory and auto-immune diseases. Schrödinger has identified structurally distinct, selective, NLRP3 inhibitors with anti-inflammatory activity in preclinical models, and is continuing to optimize peripheral and brain-penetrant leads.

Broad Portfolio Addresses Synthetic Lethality and DNA-Damage Repair

Schrödinger is advancing multiple oncology programs designed to exploit the intrinsic vulnerabilities of cancer cells through synthetic lethality and inhibition of DNA-damage repair. Today, the company is discussing its synthetic lethality programs, PRMT5-MTA and SGR-3515 (Wee1/Myt1). The company is also reviewing SGR-2921, which targets CDC7, a key regulator of replication stress and DNA-damage repair.

Schrödinger is reporting preclinical data showing that SGR-3515 has a differentiated biochemical, biophysical and functional profile, with sustained inhibition of Wee1 and Myt1 in tumor cells. Concurrent loss of function of Wee1 and Myt1 confers selective vulnerability in cancer cells and could offer increased anti-tumor activity. SGR-3515 has potential to treat a broad range of solid tumors, including uterine and ovarian cancers. Schrödinger plans to submit an IND for SGR-3515 in the first half of 2024.

Schrödinger is also discussing preclinical data presented at ASH (Free ASH Whitepaper) demonstrating that SGR-2921 exhibited better activity compared to other CDC7 inhibitors, and showed anti-proliferative effects in treatment-resistant acute myeloid leukemia (AML) patient-derived samples, as well as reduction of blasts in multiple AML models. A Phase 1 study of SGR-2921 is ongoing in patients with AML or myelodysplastic syndrome, and the company expects to report initial data from the study in late 2024 or 2025.

"CDC7 is a promising therapeutic target for the treatment of myelodysplastic syndromes and acute myeloid leukemia, diseases for which there is a significant unmet need in treating both frontline and relapsed/refractory patients," stated Elie Traer, M.D., Ph.D., associate professor at the Center for Hematologic Malignancies at Oregon Health & Science University. "Targeting CDC7 with emerging investigational therapeutics, such as SGR-2921, represents an opportunity to expand our armamentarium of treatment options beyond existing targeted therapies."

Anticipated Milestones

Today, Schrödinger outlined the anticipated milestones for its proprietary pipeline:

Report initial data from the Phase 1 study of SGR-1505 in late 2024 or 2025
Report initial data from the Phase 1 study of SGR-2921 in late 2024 or 2025
Submit IND for SGR-3515 in the first half of 2024 and initiate a Phase 1 study in 2024
Submit an IND from its discovery portfolio in 2025
Event Information

Schrödinger’s Pipeline Day will begin at 10:00 a.m. ET and is expected to conclude at approximately 12:30 p.m. ET. The live presentation can be accessed in the "Investors" section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event.