SGR-1505

Schrödinger on Thursday scrapped development of its oral CDC7 inhibitor SGR-2921 following two patient deaths in a Phase I trial for relapsed or refractory acute myeloid leukaemia (AML) or high-risk myelodysplastic syndromes (MDS).The open-label, dose-escalation study got underway in 2023 to assess safety and pharmacokinetics, with exploratory plans to test preliminary anti-tumour activity of SGR-2921 in combination with other AML/MDS treatments.The decision came despite early evidence of single-agent activity in the study, including dose-dependent reduction of AML blasts in multiple AML models and synergistic activity in combination with decitabine."Patient safety is our first priority… While disappointing given the early clinical activity observed, we believe this is the right decision," said Margaret Dugan, the company's chief medical officer.The CDC7 target is implicated in DNA replication and tumour cell proliferation. Schrödinger noted that preclinical studies had shown CDC7 inhibition could induce anti-leukaemic responses both as monotherapy and in combination with other agents in patient-derived AML models. "We had hoped to advance this investigational agent for acute myeloid leukaemia as relapse rates are high, the disease progresses rapidly and there are limited therapies available," Dugan said.The setback comes two months after Schrödinger reported early results from another oncology candidate, oral MALT1 inhibitor SGR-1505; a Phase I study for B-cell malignancies showed a 22% overall response rate across doses and a favourable safety profile. One analyst suggested at the time that SGR-1505 could be a good candidate for combination regimens with partners.The company's physics-based computational platform leverages machine learning and simulates molecular motion at the atomic level to predict properties of novel molecules (see – Spotlight On: 'A year of balance' — Realistic expectations for AI in 2025).

iStock, Olena Koliesnik After two patients who received the investigational CDC7 blocker died, pushing forward with SGR-2921’s development would be “difficult,” according to Schrödinger, whose stock dropped 17.5% before the opening bell on Thursday. Two patients have died after receiving Schrödinger’s investigational CDC7 blocker SGR-2921, being tested in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndromes. The New York–based biotech has decided to pull the plug on SGR-2921. Schrödinger had been testing SGR-2921 in a Phase I dose-escalation study, which found “early evidence of monotherapy activity,” according to a company announcement on Thursday. However, the drug was “considered to have contributed” to two patient deaths, resulting in an overall risk/benefit pro would make further development, including as part of a combination regimen, “difficult to pursue,” Schrödinger added in its statement. Chief Medical Officer Margaret Dugan said in a prepared statement on Thursday that the decision to discontinue SGR-2921 is “disappointing” but is “the right decision for patients.” Schrödinger is down 17.5% before the opening bell on Thursday. Despite losing SGR-2921, the company still has a bevy of oncology activity. In June, Schrödinger released initial Phase I data for the small molecule drug SGR-1505 in relapsed/refractory B cell malignancies, demonstrating clinical activity in different histologies, including chronic lymphocytic leukemia and Waldenström macroglobulinemia. Meanwhile, the company is trialing another small molecule, SGR-3515 for solid tumors, with preclinical data in October 2024 pointing to stronger and more durable anti-tumor activity versus previous inhibitors. The asset’s Phase I study is recruiting and has a primary completion date in October 2026. Patient deaths have captured pharma headlines in recent months, most prominent of which were the three mortalities associated with Sarepta Therapeutics’ gene therapy portfolio: two with the Duchenne muscular dystrophy treatment Elevidys and one with an investigational product for limb-girdle muscular dystrophy. On Wednesday, California-based CytomX reported one patient death linked to its antibody-drug conjugate CX-2051 being tested for colorectal cancer. A safety committee has supported the continuation of the Phase I study for the asset. Earlier this month, Allogene also reported a mortality in the Phase II study of its lymphoma CAR T cell therapy cemacabtagene ansegedleucel. The death was attributed to ALLO-647, an antibody that helps suppress the immune system in preparation for cell therapy infusion. Last week, Agios Pharmaceuticals also reported three patient deaths associated with its anemia therapy Pyrukynd. The biotech maintained that these mortalities have “not altered the established benefit-risk profile” for the drug.