FDA Clears TuHURA's IND for TBS-2025, a First-in-Class VISTA-Inhibiting Antibody in mutNPM1 AML
核心洞察
The FDA has granted TuHURA Biosciences (搜索) IND clearance and a "Study May Proceed" notice for TBS-2025 (搜索), a VISTA (搜索)-inhibiting monoclonal antibody in molecularly defined blood cancers.
A Phase 1b trial will test TBS-2025 (搜索) monotherapy at different doses in relapsed/refractory mutNPM1 AML patients who failed or relapsed after menin (搜索) inhibitor therapy.
TuHURA says it is the only known company to advance a VISTA (搜索)-inhibiting monoclonal antibody through the FDA's IND process into a Phase 1b study in mutNPM1 AML.
TuHURA Biosciences (搜索), Inc. (Nasdaq: HURA) announced on Sept. 14, 2026 that the U.S. Food and Drug Administration (搜索) has cleared its Investigational New Drug (IND) application for TBS-2025 (搜索), a VISTA (搜索)-inhibiting monoclonal antibody, for molecularly defined subsets of acute myeloid leukemia (搜索) (AML) and other blood-related cancers. The FDA's "Study May Proceed" notice allows the Tampa, Florida-based Phase 3 immuno-oncology company to begin clinical evaluation of the agent in a patient population that currently has no approved or effective treatment options.
Phase 1b Design and Patient Population
The clearance permits TuHURA to examine TBS-2025 (搜索) in a Phase 1b study evaluating the safety and potential efficacy of monotherapy at different doses in patients with relapsed/refractory (r/r) mutNPM1 AML who have failed to respond to, or relapsed after, menin (搜索) inhibitor therapy. Following review of the safety data with the FDA, the study is expected to progress to a dose-optimization stage to determine a safe and biologically effective dose.
According to the company, patients with r/r mutNPM1 AML who fail menin (搜索) inhibitor therapy have no approved or effective treatments and represent an unmet medical need. If TBS-2025 (搜索) produces encouraging response rates during the dose-optimization stage, TuHURA will explore with the FDA the potential expansion of the trial in consideration for the opportunity for accelerated approval.
"As the only known company to advance a VISTA (搜索)-inhibiting mAb through the FDA's IND process into a Phase 1b study in mutNPM1 AML, this is a major milestone for the Company and a testament to our commitment to advancing novel therapies to address the unmet needs of patients with AML," said Dr. James Bianco, President and Chief Executive Officer of TuHURA Biosciences (搜索).
VISTA as a Checkpoint Target in AML
TBS-2025 (搜索) is described by the company as a unique VISTA (搜索)-inhibiting monoclonal antibody. VISTA is a novel checkpoint expressed on quiescent (resting) T cells and highly expressed on myeloid cells, notably myeloid-derived suppressor cells (MDSCs). Scientific evidence cited by TuHURA demonstrates that mutNPM1 drives the expression of VISTA on leukemic blasts, which is reported to be the primary mechanism by which AML escapes recognition by the patient's immune system, resulting in low response rates of short duration following current therapies, including recently approved menin (搜索) inhibitors.
"Research has shown that patients whose leukemic cells express VISTA (搜索) have a poor response to therapy and significantly shorter survival," Bianco said. "Studies have demonstrated that TBS-2025 (搜索)'s ability to block VISTA on leukemic cells has resulted in dramatic improvement in survival in studies of murine models of human AML, and we hope to translate this promising underlying science into a potentially safe and effective new treatment for patients with AML."
Preclinical Rationale
The company's translational rationale rests on genetic and pharmacologic evidence in murine models. When VSIR (搜索), the gene encoding VISTA (搜索), is edited so as not to produce VISTA in murine models of mutNPM1 AML, an immune response is observed and survival is enhanced. In a murine model of AML, TBS-2025 (搜索) resulted in an increase in survival comparable to the intensive chemotherapy regimen currently used in front-line treatment of patients with AML, and when combined with intensive chemotherapy, survival was markedly improved. TuHURA states that these data collectively underscore the potential for TBS-2025 in the treatment of patients with AML.
Broader Pipeline Context
TuHURA positions itself as a Phase 3 immuno-oncology company developing novel technologies to overcome primary and acquired resistance to cancer immunotherapy, which it identifies as two of the most common reasons cancer immunotherapies fail to work or stop working in the majority of patients with cancer. Its lead innate immune agonist, IFx-2.0, is designed to overcome primary resistance to checkpoint inhibitors, and the company has initiated a single randomized placebo-controlled Phase 3 registration trial of IFx-2.0 administered as an adjunctive therapy to Keytruda (pembrolizumab) compared with Keytruda plus placebo in first-line treatment for advanced or metastatic Merkel cell carcinoma (搜索).
Beyond TBS-2025 (搜索), which the company describes as moving into Phase 1b/2 in mutNPM1 r/r AML, TuHURA is leveraging its Delta Opioid Receptor technology to develop first-in-class, bi-specific, bi-functional antibody-drug conjugates (ADCs) targeting myeloid-derived suppressor cells to inhibit their immune-suppressing effects on the tumor microenvironment, with the aim of preventing T cell exhaustion and acquired resistance to checkpoint inhibitors and cellular therapies.
The company notes that its statements regarding the planned Phase 1b study of TBS-2025 (搜索) are forward-looking and subject to risks including those associated with conducting the trial, patient enrollment, trial design, data outcomes, regulatory interactions, and uncertainty regarding the timing and likelihood of regulatory approvals.