Curis Reports Promising MRD Conversion Data for Emavusertib in AML Combination Therapy
核心洞察
Curis (搜索) presented preliminary data from its AML triplet study showing 62.5% of patients achieved MRD conversion from positive to undetectable when emavusertib was added to azacitidine and venetoclax therapy.
The company is strategically pivoting to focus on combination therapies targeting both BCR (搜索) and TLR (搜索) pathways simultaneously, prioritizing NHL subtypes including PCNSL and CLL over AML development.
Curis (搜索) secured $80.8 million in potential funding through a PIPE financing, with additional tranches tied to clinical milestones, providing a cash runway into the second half of 2027.
Curis (搜索) Inc. has reported encouraging preliminary results from its AML triplet study, demonstrating that the addition of emavusertib to standard azacitidine and venetoclax therapy can achieve meaningful disease clearance in acute myeloid leukemia patients. The data, presented at the 67th ASH Annual Meeting in December, showed that five of eight evaluable patients (62.5%) achieved MRD conversion from positive to undetectable levels.
Clinical Data Shows Promise for Disease Modification
The AML triplet study (CA-4948-104) evaluated emavusertib in combination with azacitidine and venetoclax in AML patients who had achieved complete remission on the standard aza-ven combination but remained MRD-positive. The study tested two dosing schedules, with patients receiving emavusertib for either 7 or 14 days in a 28-day cycle alongside their existing treatment.
Dr. Christina Papayannidis from IRCCS Azienda Ospedaliero Universitaria di Bologna presented the poster titled "Preliminary Pharmacokinetic and MRD Results from AML Patients Treated with 7- and 14-Day Dosing Schedule of Emavusertib added to Combination Therapy with Azacitidine and Venetoclax." The results included 4 patients in the 7-day cohort and 6 patients in the 14-day cohort, with 8 patients having central MRD samples available for analysis.
Strategic Shift Toward Combination Therapies
Curis (搜索) management outlined a strategic pivot from monotherapy to dual-blockade approaches, combining emavusertib with BTK (搜索) inhibitors to target both BCR (搜索) and TLR (搜索) pathways simultaneously. This strategy addresses what the company identifies as a critical gap in current CLL standard of care, where BTK inhibitor monotherapy typically achieves only partial responses and leads to chronic treatment dependency.
"We know there are two pathways driving disease in these patients—the BCR (搜索) pathway and the TLR (搜索) pathway," explained CEO James E. Dentzer during the company's earnings call. "Historically, the standard of care is BTKi. BTKi blocks the BCR pathway, and it works; you are blocking one of the two pathways driving disease. That said, it is also why patients are only getting partial response; they are not getting complete remission because they are only blocking one of the two pathways."
Prioritizing NHL Development Over AML
The company is strategically prioritizing Non-Hodgkin Lymphoma subtypes, specifically primary central nervous system lymphoma (PCNSL) and chronic lymphocytic leukemia (CLL), over continued AML development. Management cited both the high unmet medical need in PCNSL and the significant market scale of CLL as driving factors in this decision.
"We are definitely prioritizing NHL ahead of AML," Dentzer stated. "Right now, we have a dual-pronged strategy where we are pushing forward very aggressively in PCNSL—that is one of the smallest and most rare of the subtypes of NHL—as well as CLL, which is inarguably the largest."
The TakeAim Lymphoma study in PCNSL is designed as a single-arm registrational trial intended to support accelerated approval submissions in both the US and Europe. Full enrollment is projected within a 12-to-18-month window, potentially enabling a regulatory filing in 2027 after six months of patient follow-up.
Financial Position and Clinical Timeline
Curis (搜索) secured significant funding through a January 2026 private placement, raising gross proceeds of up to $80.8 million. The financing includes initial proceeds of approximately $20.2 million with three series of warrants that can be exercised for up to $20.2 million each. Notably, the Series B warrants are tied to clinical milestones, terminating 30 days after the company announces dosing of the fifth patient in the Phase 2 CLL trial.
The company believes its current cash position, combined with the initial PIPE proceeds and expected additional funding from warrant exercises, should enable planned operations into the second half of 2027.
For the year ended December 31, 2025, Curis (搜索) reported a net loss of $7.6 million, or $0.58 per share, compared to a net loss of $43.4 million, or $6.88 per share, in 2024. The improved financial position was partly due to operational efficiency improvements, with research and development expenses decreasing from $38.6 million to $28.3 million year-over-year.
Upcoming Clinical Milestones
Initial data from the CLL proof-of-concept study is expected to be presented at the ASH Annual Meeting in December 2026. The study aims to demonstrate whether dual pathway inhibition can deepen responses from partial remission to complete remission with MRD negativity.
"We are aiming to deepen that response and see that patients are moving toward a complete remission and, hopefully, MRD negativity," explained Chief Medical Officer Ahmed M. Hamdy. "We are aiming to inhibit the NF-kappa B (搜索) pathway, which is a driver of the disease, at a much deeper level."
Emavusertib, an orally available small molecule IRAK4 (搜索) and FLT3 (搜索) inhibitor, has received Orphan Drug Designation from the U.S. FDA for the treatment of PCNSL, AML, and MDS, as well as from the European Commission for PCNSL treatment.