TuHURA Biosciences outlines development pathway for IFx-2.0

TuHURA Biosciences (HURA) provided a business update and outlined upcoming targeted milestones. “We have made significant progress toward accomplishing our 2024 corporate objectives, including reaching a Special Protocol Assessment agreement with the FDA by working with the Oncology Center of Excellence and FDA’s Project Front Runner initiative for a novel Phase 3 trial design for IFx-2.0 under the FDA’s accelerated approval pathway. This single registration directed trial, in addition to its primary endpoint of Overall Response Rate, it will also incorporate a key secondary endpoint of Progression Free Survival that, if achieved, can satisfy the requirement for a post-approval confirmatory trial, potentially converting accelerated approval to full approval,” commented James Bianco, CEO. “We have also advanced our efforts toward the potential acquisition of KVA12123, a novel VISTA inhibiting antibody, with a non-binding letter of intent, which would bring to our pipeline a Phase 2 ready candidate with therapeutic synergies across our pipeline and technologies, all while becoming a NASDAQ-listed Company after having raised significant capital adequate to advance our current programs late into the second half of 2025.” Innate Immune Response Agonists: TuHURA’s IFx technology utilizes a proprietary plasmid DNA or messenger RNA which, when introduced into or targeted to a tumor, results in the expression of a highly immunogenic gram-positive, bacterial protein on the surface of the tumor cell, making the tumor look like a bacterium. Gram-positive bacterium has molecular patterns, or motifs, preserved over evolution which are recognized by receptors on our immune cells called toll like receptors. TLR 2 specifically recognizes the pattern of gram-positive bacterial proteins, like Emm55 leading to the activation of antigen presenting cells. Once activated, APCs digest the tumor cell and present non-self, tumor neoantigens to newly produced T and B cells, activating a tumor-specific adaptive immune response. Through its activation of tumor specific T cells, IFx-2.0 administration can potentially overcome primary resistance to checkpoint inhibitors. TuHURA is preparing to initiate a single, randomized, placebo-controlled Phase 3 accelerated approval trial of IFx-2.0 administered as an adjunctive therapy to Keytruda versus pembrolizumab plus placebo in first line treatment for checkpoint inhibitor-naive patients with advanced or metastatic MCC. The data from the Company’s Phase 1b trial in patients with advanced or metastatic MCC who exhibited primary resistance to CPI was used to support a potential single registration directed trial. Consistent with the FDA’s Project Front Runner Initiative, the FDA’s OCE recommended investigating IFx-2.0 in the first line setting rather than in patients progressing on first line therapy. Project Front Runner is an FDA OCE initiative to encourage drug sponsors to consider when it may be appropriate to first develop and seek approval of new cancer drugs for advanced or metastatic disease, in an earlier clinical setting rather than the usual approach to develop and seek approval of a new drug for treatment of patients who have received numerous prior lines of therapies or have exhausted available treatment options. The FDA also encouraged the Company to consider designing the trial to include a key secondary endpoint shown to be of clinical benefit like PFS allowing this accelerated approval trial to potentially satisfy both the requirements for accelerated approval based on ORR, while satisfying the requirement for a post-approval confirmatory trial if the secondary PFS endpoint is achieved. The trial will be conducted under an SPA agreement with the FDA. Tumor Microenvironment Modulators: Leveraging its Delta receptor technology, TuHURA is developing bi-specific immune modulating ADCs or PDCs targeting MDSCs to inhibit their immune suppressing effects on the tumor microenvironment to prevent T cell exhaustion and acquired resistance to checkpoint inhibitors and cellular therapies. Potential Acquisition of Novel Anti-VISTA Checkpoint Inhibitor: As previously announced on July 8, 2024, TuHURA entered into an Exclusivity and Right of First Offer Agreement with Kineta for the potential acquisition of Kineta’s KVA12123 VISTA inhibiting antibody. TuHURA has continued to engage in discussions and negotiations with Kineta and has entered into a non-binding letter of intent regarding a potential transaction in which TuHURA would acquire the rights to KVA12123 for a combination of cash and shares of TuHURA common stock via a merger transaction structure. KVA12123 has completed enrollment in its monotherapy arm, demonstrating safety at its highest dose level. Kineta anticipates completion of enrollment in the combination therapy arm where KVA12123 is administered with Merck’s anti-PD1 therapy, KEYTRUDA. Initial results were reported earlier this year at the American Association of Cancer Research Annual Meeting 2024 and recently at the Society for Immunotherapy of Cancer meeting.