TuHURA Files IND for TBS-2025 in Combination with Menin Inhibitor for mutNPM1 r/r AML

TuHURA Biosciences has filed an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration's Division of Hematologic Malignancies 1 (DHM1) for the study of TBS-2025, a novel VISTA inhibiting antibody, for the treatment of mutNPM1 relapsed/refractory (r/r) acute myeloid leukemia (AML) in combination with a menin inhibitor.

The company plans to initiate a Phase 2 study in menin inhibitor-naïve patients with mutNPM1 r/r AML utilizing a Simon 2-stage design. Pending completion of FDA review and clearance, the company currently targets initiating the Phase 2 study in early Q2 2026, with preliminary Stage 1 results in Q3 2026.

"While the introduction of menin inhibitors for the treatment of mutNPM1 r/r AML has provided these patients with the first approved therapy, CR/CRh rates across the class are generally <25% and of short duration, underscoring the continued unmet medical need," stated the company's president and chief executive officer. He added that adding TBS-2025 to a menin inhibitor may markedly increase both the CR/CRh rate and its duration, and that if successful, the company would seek FDA guidance on developing TBS-2025 under the FDA's accelerated approval pathway.

VISTA is a novel checkpoint expressed on quiescent T cells and highly expressed on myeloid cells. Scientific evidence demonstrates that mutNPM1 and mutDNM3TA, two of the most common mutations in AML and other myeloid malignancies, may drive the expression of VISTA on leukemic blasts and are reported to be the primary mechanisms by which AML has a poor response to and high relapse rate following current therapies. VISTA expression is linked to high relapse rates in AML due to its ability to allow leukemic blasts to evade immune recognition and attack by the patient's immune system. When VSIR, the gene that encodes for VISTA, is removed in murine models of mutNPM1 AML, an immune response is observed and survival is enhanced.

TBS-2025 was initially investigated by Kineta in a large Phase 1 trial either as monotherapy (n=24) or in combination with pembrolizumab (n=15) among patients with advanced, therapy-refractory cancers, including breast, lung, colorectal, and ovarian cancers. The drug demonstrated a favorable safety profile even at the highest dose level of 1,000 mg administered every two weeks. Based on pharmacokinetics and pharmacodynamics, the optimal Phase 2 dose is believed to be 750 mg every three weeks. TBS-2025 was acquired by the company in its acquisition by merger with Kineta Inc. on June 30, 2025.

TuHURA is a Phase 3 immuno-oncology company developing novel therapeutics to overcome resistance to cancer immunotherapy. Its lead innate immune agonist, IFx-2.0, is being evaluated in a single randomized placebo-controlled Phase 3 registration trial as an adjunctive therapy to pembrolizumab compared to pembrolizumab plus placebo in first-line treatment for advanced or metastatic Merkel cell carcinoma. The company is also leveraging its Delta Opioid Receptor technology to develop first-in-class, bi-specific, bi-functional antibody-drug conjugates targeting myeloid-derived suppressor cells.