Schrödinger Halts CDC7 Inhibitor Program After Patient Deaths in Phase 1 Trial

Schrödinger, a biotech company known for its computational drug discovery platform, has announced the discontinuation of its CDC7 inhibitor program following two patient deaths in a phase 1 clinical trial. The decision marks a significant setback for the company and raises questions about the future of CDC7 inhibition as a therapeutic approach.

Trial Termination and Safety Concerns

Schrödinger revealed that it is abandoning its CDC7 inhibitor, SGR-2921, after the therapy was linked to the deaths of two patients in an early-stage study. The trial was evaluating the drug in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes.

According to the company's August 14 release, two AML patients in the trial died, with SGR-2921 "considered to have contributed" to the fatalities. This development, combined with the drug's overall profile observed to date, led Schrödinger to discontinue the program entirely.

Margaret Dugan, M.D., Schrödinger's Chief Medical Officer, emphasized the company's commitment to patient safety, stating, "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."

Implications for CDC7 Inhibition Research

The termination of Schrödinger's CDC7 inhibitor program highlights the challenges faced by researchers in this field. For over two decades, biopharma companies have been investigating the potential of CDC7 inhibition, yet none of these programs have advanced to late-stage studies.

Schrödinger had previously touted SGR-2921 as "the most potent CDC7 inhibitor reported to date," citing its strong drug-like characteristics. The company had also reported "early evidence of monotherapy activity" and suggested that pharmacological data indicated a "favorable, differentiated profile with best-in-class potential."

However, the recent patient deaths have cast doubt on the viability of CDC7 inhibition as a therapeutic strategy, at least in the near term. Schrödinger now believes that "the path to development as a combination therapy would be difficult to pursue," further limiting the potential applications of this approach.

Schrödinger's Ongoing Clinical Programs

Despite this setback, Schrödinger maintains an active clinical pipeline with two other cancer drugs currently in development:

1. SGR-1505: A MALT1 inhibitor in phase 1 studies for relapsed/refractory B-cell lymphomas.
2. SGR-3515: A Wee1/Myt1 inhibitor undergoing early-stage studies in patients with advanced solid tumors.

The company's focus will likely shift to these remaining candidates as it seeks to advance its clinical-stage portfolio and demonstrate the value of its computational drug discovery platform.