SGR-2921

Schrödinger had previously been expecting a readout from the trial in the final months of the year.\n Schrödinger is abandoning its CDC7 inhibitor after the therapy was linked to the deaths of two patients in a phase 1 leukemia trial.The biotech had been evaluating the asset, dubbed SGR-2921, in an early-stage study of patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes.Schrödinger revealed in an Aug. 14 release that two of the patients with AML have died, with SGR-2921 “considered to have contributed” to the fatalities. The deaths, when considered alongside the drug’s “profile observed to date,” mean the biotech is discontinuing the program.Biopharmas have been investigating the potential of inhibiting CDC7 for over 20 years, but none of these programs have made it into late-stage studies. When launching the phase 1 study, Schrödinger said that its digital platform had enabled the company to create SGR-2921, which it branded “the most potent CDC7 inhibitor reported to date and possess[ing] strong drug-like characteristics.”The company had previously been expecting a readout from the trial in the final months of the year, having alluded to “early evidence of monotherapy activity” from the study. Executives had previously touted pharmacological data as suggesting that the CDC7 inhibitor had a “favorable, differentiated profile with best-in-class potential.”While the initial strategy for SGR-2921 had included combining it with standard-of-care agents, the company said in this morning’s release that it now believes “the path to development as a combination therapy would be difficult to pursue.” “Patient safety is our first priority, and in light of two treatment-related deaths in the phase 1 dose-escalation study, we have made the decision to discontinue further development of SGR-2921,” Schrödinger Chief Medical Officer Margaret Dugan, M.D., said in the release.“While disappointing given the early clinical activity observed, we believe this is the right decision for patients,” Dugan added. “We had hoped to advance this investigational agent for acute myeloid leukemia as relapse rates are high, the disease progresses rapidly and there are limited therapies available.”With SGR-2921 discarded, Schrödinger still has two other cancer drugs in the clinic, including a MALT1 inhibitor called SGR-1505 in a phase 1 study for relapsed/refractory B-cell lymphomas. There’s also SGR-3515, a Wee1/Myt1 inhibitor undergoing an early-stage study in patients with advanced solid tumors.

Schrödinger is discontinuing work on an experimental medicine for certain blood cancers after treatment with the drug resulted in two deaths in an early-stage trial. The computation drug company had been studying the candidate, called SGR-2921, in a Phase 1 trial. It recruited patients whose acute myeloid leukemia had returned or progressed, and in patients with myelodysplastic syndromes who were at high risk of developing AML. Schrödinger said there were “two emergent events” where the experimental drug was believed to have led to the deaths of two AML patients, but the biotech did not say in its Thursday announcement what those events were and whether they were the same. The drug was designed to block a protein that’s key to the cell cycle called CDC7. A Schrödinger spokesperson declined to share additional details on the patient deaths, but said that targeting CDC7 “has the potential to be immunosuppressive.” That effect, which is also seen in other blood cancer therapies, increases the risk of severe infections, the spokesperson said. The company had plans to investigate the drug in a combination approach, but said that path “would be difficult to pursue.” The Phase 1 dose-escalation trial aimed to recruit a total of 50 participants. “While disappointing given the early clinical activity observed, we believe this is the right decision for patients,” chief medical officer Margaret Dugan said in the release.