NASDAQ:HURA
READ THE FULL HURA RESEARCH REPORT
We are initiating coverage of TuHURA Biosciences, Inc. (NASDAQ:HURA) with a valuation of $9.25 per share. This value is based on our estimates for successful development and commercialization of IFx-2.0 in patients with Merkel cell carcinoma (MCC) and KVA12 which will be advanced in acute myeloid leukemia (AML). IFx-2.0 is scheduled to begin its Phase III study in 1H:25 under a Special Protocol Assessment (SPA) agreement with the FDA. The trial will benefit from the FDA’s Project FrontRunner initiative which will allow IFx-2.0 to be evaluated in an earlier clinical setting with only one Phase III required for accelerated approval. The recently acquired anti-V-domain Immunoglobulin suppressor of T-cell activation (VISTA) asset is completing a Phase I dose-finding study in advanced solid tumors. This class of biologic may work particularly well in blood cancers with mutated nucleophosmin 1 (NPM1). The antibody may be combined with a delta opioid receptor (DOR) inhibitor and/or a menin inhibitor in future studies if supported by clinical work. TuHURA will pursue an indication in AML, where there is evidence of a signal. A Phase IIa/b trial for the candidate in mutated NPM1 (mNPM1) AML is slated to begin later this year following the close of the merger with Kineta. TuHURA’s antibody-drug conjugate (ADC) is expected to traverse a novel route in this space, binding to the DOR and carrying an immunotherapy, possibly TuHURA’s very own anti-VISTA agent. We see the ADC asset as a desirable partnering asset with established biopharma companies.
IFx-2.0 is an intratumorally injected plasma DNA (pDNA) that infects cancer cells to produce bacterial proteins on their surface. These proteins stimulate an innate immune response which destroys cancer cells and subsequently activates an adaptive immune response to overcome resistance. TuHURA has demonstrated safety and proof of concept in several small early-stage trials. To date, the company has completed four Phase I studies. They have shown an overall response rate (ORR) for MCC in many subjects. The dose escalation portion of the study established that IFx-2.0 was well-tolerated at all dose levels. Further study evaluated MCC patients who had previously received checkpoint therapy. Results showed that IFx-2.0 may overcome primary resistance to checkpoint inhibitor therapy and may provide support for administering the agent before checkpoint inhibitor therapy to increase response rates.
Recent research has shown a correlation between high NPM1 mutations and VISTA expression, particularly in AML. As mutated NPM1 (mNPM1) drives leukemogenesis through menin and the efficacy of menin inhibitors in producing treatment responses in mNPM1-associated AML, combination therapy using a VISTA-inhibiting antibody is a promising approach to improve response rates in AML. In 2H:25, TuHURA expects to evaluate this further with a proof-of-concept study. The anti-VISTA asset may be considered as a monotherapy or in combination with the ADC or IFx programs.
Merkel cell carcinoma (MCC) is a type of skin cancer originating from Merkel cells and can grow rapidly if not treated. While a relatively high proportion of MCC patients respond to checkpoint inhibitors, there remains an unmet need in patients that do not respond or those that relapse. The annual incidence of MCC is about 3,300 persons in the United States and 4,500 in Europe and Australia.
Acute myeloid leukemia (AML) has a substantially higher incidence than MCC with over 20,000 cases per year and global incidence of about 1.5 per 100,000. AML is a cancer of the blood and bone marrow where immature blood cells proliferate and interfere with normal blood cell production. It primarily affects white blood cells called myeloid cells and progresses quickly without treatment. About a third of AML patients carry the NPM1 mutation, which drives overexpression on AML blasts, most of which, coincidentally, have high VISTA expression.
In addition to the lead programs for IFx-2.0 and VISTA, TuHURA has a portfolio of other programs in line for further development or divestiture. The IFx-3.0 program seeks to achieve intravenous delivery of the Emm55 mRNA targeting CD22, which is overexpressed on cancerous B-cells. The antibody-drug conjugate (ADC) program features a delta-receptor-selecting-small-molecule designed to target myeloid derived suppressor cells (MDSCs) and counteract their immunosuppressive effect. As part of its merger with Kintara, TuHURA inherited a photodynamic therapy for unresectable cutaneous metastatic breast cancer (CMBC) designated REM-001. The asset is in a small proof of concept trial that, if successful, will qualify Kintara shareholders for a contingent value right (CVR) to be paid in shares. Another party will advance REM-001 beyond this point.
Based on the strong data generated, TuHURA recently raised $31 million as part of the reverse merger into Kintara last October. $15 million was spent to acquire Kineta in cash and stock. In addition to the cash on hand, TuHURA may raise additional funds via the private investment in public equity (PIPE) route. Company management has stated that it has sufficient capital to fund operations into late 2025. We expect another capital raise to provide further financial support for the pipeline programs.
TuHURA has outlined a plan for 2025 to initiate the IFx-2.0 Phase III trial, begin the KVA12 Phase II trial in mutated NPM1 AML and conduct further preclinical research in its IFx-3.0 and targeted ADC programs. The company expects that it will be able to fully enroll the IFx-2.0 trial within twelve months of dosing the first patient. Six months later, topline results can be available for regulatory submission. Accelerated approval will allow for an expedited review of the application, a timeline that, if everything goes as planned, could support marketing IFx-2.0 about two years after starting the trial. KVA12’s pathway could be similarly streamlined after a short proof-of-concept trial slated for 2H:25.
We expect further updates to provide specific timing for the pipeline programs throughout 2025 and should see clinical trial updates at society events including AACR, ASCO, ESMO, SITC and ASH.
Key reasons to own TuHURA Biosciences shares:
- IFx-2.0 offers the potential to overcome resistance to immunotherapies
- Employs an pDNA that produces a bacterial protein on the tumor cell
- Overcomes tumor resistance mechanisms
- Provides synergies with checkpoint inhibitors
- Activates both the innate and adaptive immune systems
- Credible 24-month study timeline to approval
- Recently acquired VISTA asset
- Addresses mechanism of cancer immune resistance
- Limited competition from other VISTA assets
- Integrates innate and adaptive immune responses
- Demonstrates synergies with checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4)
- Favorable safety profile with no evidence of cytokine release syndrome (CRS)
- Can be used as monotherapy or in combination with other TuHURA assets
- Offers preclinical programs that address shortcomings in other therapies
- IFx-3.0 tumor-targeted mRNA
- Bi-specific antibody and peptide drug conjugates (ADCs & PDCs)
- Access to expedited treatment from the FDA
- Single Phase III accelerated approval for IFx-2.0
- Special Protocol Assessment agreement with FDA
- Visibility to accelerated approval pathway for VISTA in AML
- Robust intellectual property
- Over 40 IFx platform patents internally owned
- DOR & ADC patents jointly owned with West Virginia University & Moffitt Cancer Center
- Acquired Kineta patents for anti-VISTA antibodies
In our initiation report, we introduce immuno-oncology, paying particular attention to innate immune agonists and checkpoint inhibitors. We examine the innate and adaptive immune systems work together to generate abscopal effects throughout the body. We follow with a description of TuHURA’s therapeutic candidates including IFx-2.0, KVA12, ADCs and the next generation IFx-3.0 infused therapy. The following chapter reviews the company’s clinical programs including IFx-2.0 Phase I and anticipated Phase III study and KVA12 which has completed a Phase I and is preparing for a Phase II. We also include a brief description of TuHURA’s other assets including the ADC and IFx-3.0 programs. The next part discusses the primary indications being pursued in MCC and AML. The epidemiology, etiology and other details of these indications are included. This is followed by a short summary of TuHURA’s intellectual property (IP), Project Frontrunner and the SPA for IFx-2.0. We then discuss other competitors in the immuno-oncology space, including peers advancing innate immune agonists and anti-VISTA programs. The subsequent section reviews TuHURA’s recent financial and operational history followed by an introduction to the management team and an analysis of company-specific risks. Our valuation discussion details the assumptions behind our target price. Our work generates a valuation of $9.25 per share.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR.Â
DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.
