ALLO-647

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.

iStock, Andrii Yalanskyi While the deaths occurred in patients who had been treated with Agios’ anemia treatment Pyrukynd, the biotech insisted in an SEC filing midday Monday that the drug’s risk-benefit pro unchanged. Shares of Massachusetts-based Agios Pharmaceuticals were put through the wringer on Monday after the FDA’s Adverse Event Reporting System revealed four deaths in patients who had taken its anemia drug Pyrukynd. Leerink analysts flagged a 23% dip at the stock’s lowest point, with share prices hitting $26.75 at market opening Monday before rebounding to $36.16 by the closing bell, a 3% increase from its closing price last Friday. In pre-market trading Tuesday, Agios shares have dipped 2% Agios filed an SEC document on Monday to address the four deaths, which were first made public by a securities analyst who filed a Freedom of Information Act request to the FDA’s safety database, to which Agios had reported these deaths. In its regulatory filing, Agios reassured investors that the deaths have “not altered the established benefit-risk profile” for Pyrukynd. Two of the deaths were in older patients: one in a 61-year-old man and another in a 93-year-old woman, both of whom were being treated for pyruvate kinase (PK) deficiency. Agios reported these cases to the FAERS on June 28, 2024 and July 17, 2025, respectively, according to the Leerink analysts. The last two fatalities were in much younger women, a 28-year-old and a 26-year-old, who had sickle cell disease and were being treated with Pyrukynd under compassionate use. The latter of these two cases was reported to the FDA on July 15 this year. Leerink said that these latter two deaths are “concerning given the young age of the patients.” But after following up with Agios, the analysts learned that these two younger patients were actually the same person. “The 28-year-old patient was actually a duplicate of the 26-year-old patient which was incorrectly entered into the database,” the Leerink note read, adding that this has in turn “largely offsets our concerns” that these deaths represent “a heightened mortality risk of Pyrukynd.” Despite Agios’ clarifications, “it is difficult to fully dismiss the impact of the safety concerns” on an upcoming PDUFA data for Pyrukynd, Leerink added. Agios is proposing Pyrukynd for the treatment of patients with alpha- or beta-thalassemia regardless of their dependence on transfusions. The FDA is expected to release its verdict on Sept. 7 . The drug was first approved in 2022 for adults with hemolytic anemia with PK deficiency. Patient deaths have been in the news in recent months, the most visible of which have been the three mortalities linked to Sarepta’s gene therapy portfolio: two to its Duchenne muscular dystrophy product Elevidys and one to an investigational limb-girdle muscular dystrophy candidate. Then, late last week, Allogene Therapeutics likewise reported a patient death in a Phase II study of its CAR T therapy cemacabtagene ansegedleucel, though the fatality was ultimately linked to ALLO-647, an anti-CD52 antibody used as an immunosuppressive treatment to prepare patients for the cell therapy.