Schrödinger has discontinued development of its investigational CDC7 blocker SGR-2921 after two patient deaths in a Phase I dose-escalation study for blood cancers. The New York-based biotech made the decision following safety concerns in patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes.
Safety Concerns Lead to Program Termination
The Phase I trial (NCT05961839) had initially demonstrated "early evidence of monotherapy activity," according to Schrödinger's Thursday announcement. However, the drug was "considered to have contributed" to two patient deaths, creating an overall risk/benefit profile that would make further development "difficult to pursue," including as part of a combination regimen.
Chief Medical Officer Margaret Dugan emphasized patient safety as the primary concern in the decision. "Patient safety is our first priority, and in light of two treatment-related deaths in the Phase I dose-escalation study, we have made the decision to discontinue further development of SGR-2921," Dugan stated. "While disappointing given the early clinical activity observed, we believe this is the right decision for patients."
Market Impact and Company Response
The announcement significantly impacted Schrödinger's stock performance, with shares falling 17.5% before the opening bell on Thursday. The company's stock opened 12.19% down, dropping from a $19.84 close on August 13 to a $17.42 open on August 14.
Despite the setback with SGR-2921, Schrödinger maintains an active oncology pipeline. In June, the company released initial Phase I data for SGR-1505, a small molecule drug being tested in relapsed/refractory B cell malignancies. The therapy demonstrated clinical activity across different histologies, including chronic lymphocytic leukemia and Waldenström macroglobulinemia.
Continued Pipeline Development
The company is also advancing SGR-3515 for solid tumors, with preclinical data from October 2024 showing stronger and more durable anti-tumor activity compared to previous inhibitors. The asset's Phase I study is currently recruiting patients and has a primary completion date scheduled for October 2026.
Broader Industry Safety Challenges
The SGR-2921 discontinuation adds to recent safety concerns across the pharmaceutical industry. Patient deaths have captured headlines in recent months, including 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.
California-based CytomX reported one patient death linked to its antibody-drug conjugate CX-2051 being tested for colorectal cancer, though a safety committee supported continuation of the Phase I study. Allogene also reported a mortality in the Phase II study of its lymphoma CAR T cell therapy cemacabtagene ansegedleucel.
Unmet Medical Need in AML
The discontinuation of SGR-2921 highlights the ongoing challenges in treating relapsed/refractory AML, where therapeutic options remain limited. Dugan noted the company "had hoped to advance this investigational agent for AML as relapse rates are high, the disease progresses rapidly, and there are limited therapies available."
Current approved therapies for r/r AML include Astellas' Xospata (gilteritinib), Agios Pharmaceuticals' Tibsovo (ivosidenib), and Pfizer's Mylotarg (gemtuzumab ozogamicin), though these target specific AML mutations. AbbVie's Venclexta (venetoclax) and hypomethylating agent combinations are prescribed off-label in this patient population.
According to GlobalData, the AML market is projected to reach $3.68 billion by 2032 across eight major markets, including the US, France, Germany, Italy, Spain, UK, Japan, and China. Recent developments in the space include Sellas Life Sciences' CDK9 inhibitor SLS009 (tambiciclib), which achieved a mean overall response rate of 33% in a Phase Ia/II trial, exceeding the 20% threshold.
