Fimepinostat

Curis’ decision to advance emavusertib over others is based on data that was just received from the phase 1/2 TakeAim Leukemia study, which is due to be presented at the upcoming American Society of Hematology meeting in December. Curis had some tough decisions to make to ensure its leukemia drug could survive, but the data were clear: The company needed to rally behind the med, and, in today’s biotech landscape, that means layoffs and a slimming of other programs. The Lexington, Massachusetts-based company is cutting 30% of its workforce and reallocating resources to focus solely on emavusertib, which is currently in a phase 1/2 trial for acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), and another phase 2 study called LUCAS for patients with lower-risk MDS. The cuts were announced in a third-quarter earnings report Wednesday afternoon.  The decision to advance emavusertib over the others is based on data that was just received from the phase 1/2 TakeAim Leukemia study, which is due to be presented at the upcoming American Society of Hematology meeting in December. Curis will present data on 11 additional evaluable patients treated with emavusertib alone and in combination with AbbVie and Genentech’s Venclexta. It’s the same trial that was stymied by an FDA hold earlier this year after a patient death spurred a safety review. The agency followed up the April hold with a second partial hold on the similar TakeAim Lymphoma trial. Both were lifted in August after the FDA conducted a safety review and collected additional information from Curis on the patient, who experienced rhabdomyolysis—a known dose-limiting toxicity of emavusertib that leads to the breakdown of skeletal muscle. The review also produced a rhabdomyolysis identification and management strategy for future patients. CEO Jim Dentzer acknowledged the tough decision to lay off workers but highlighted the unmet need in relapsed/refractory AML or MDS and said emavusertib could be a “game-changing therapy.” “I'd like to acknowledge that while we are excited about the heightened focus of emavusertib, we understand the impact of deprioritizing our other programs has on our valued colleagues and friends who worked on them,” Dentzer said during a third-quarter earnings call Wednesday afternoon. The cuts will allow Curis to extend its cash runway into 2025, Dentzer said. As of the end of September, Curis had $98.7 million in cash, cash equivalents and investments. Dentzer said the reduction will be across the company, in both R&D and administrative roles, and will focus on “everything that’s not directly related to emavusertib.” “Anything that wasn’t directly related was something that we could live without,” he said. “And if we could live without it and that extended our cash runway without having to do anything else—I mean this is the luxury of starting with such a strong balance sheet that we have this flexibility.” He again stressed that the data to come would make clear that all efforts need to shift behind emavusertib. “With these data in it becomes increasingly clear that this is a drop and this needs to get to NDA submission with haste,” Dentzer said of the efficacy results seen in the emavusertib data to come. “So we’re going to dedicate and redouble all of our efforts to make that happen and insulate ourselves from the need to raise money in the meantime.” The cuts will begin in the fourth quarter. Curis has four other therapies listed on its pipeline, including the early-stage diffuse large B-cell lymphoma treatment fimepinostat and CI-8993 in VISTA-expressing cancers. Dentzer said that the CI-8993 program will be “more of a pause” with no new patients being enrolled. The pending data on emavusertib were just too strong and puts the company on the precipice of a new drug filing. “If you can’t afford to do both, boy, the decision is clear, you go with the one that’s got the proven data,” Dentzer said. The CEO also gave some additional color on the nature of the FDA hold. While the patient death was a major part of the FDA’s review, he also said the agency had questions about dosing under its Project Optimus, which aims to find the lowest effective dose for newer cancer treatments. Curis tested three different doses ranging from 200 mg to 400 mg, which all have shown responses. The FDA wanted to be involved in the process to determine which dose moved forward in further testing: “That's the perfect place for FDA to want to sink their teeth in,” Dentzer said. In the end, Curis enrolled nine new patients at the lowest dose to help determine the correct amount to move forward with in phase 2. Dentzer said the hope is to have those new patients enrolled by the midpoint of next year, which will allow conversations about a new drug application to fire up. Curis' shares fell just over 7% as the market closed Wednesday to 72 cents compared with a previous open of 77 cents.