TuHURA Biosciences Discovery Research on Targeting the Delta Opioid Receptor (DOR) to Reprogram Myeloid-Derived Suppressor Cells (MDSCs) Selected for Oral Presentation at the 67th ASH Annual Meeting and Exposition

Oral presentation highlights the first time it's been demonstrated that the DOR is expressed on tumor-associated MDSCs, and that DOR inhibition reprograms multiple mechanisms of MDSC- induced immunosuppression representing a new target in overcoming acquired resistance to cancer immunotherapy

The first demonstration that DOR is expressed on Tumor-Associated Macrophages (TAMs), with DOR inhibition modulating their immunosuppressive capabilities

Presentation from The Moffitt Cancer Center in collaboration with TuHURA scientists demonstrating the presence of the DOR on MDSCs from patients with myeloid dysplastic syndrome (MDS) and restoration of stem cell proliferation with DOR inhibition

TAMPA, Fla., Nov. 3, 2025 /PRNewswire/ -- TuHURA Biosciences, Inc. (NASDAQ: HURA) ("TuHURA"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, today announced that its research on the potential role of the Delta Opioid Receptor in controlling the immunosuppressive capabilities of MDSCs was accepted for an oral presentation at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Orlando, FL from December 6-9, 2025. TuHURA will present these updated results along with a poster presentation of the effects of DOR inhibition on TAMs, another immunosuppressive cellular component critical to the tumorigenic microenvironment.

"We are pleased to present evidence demonstrating the expression of the DOR on MDSCs and TAMs, both of which are important immune suppressing cellular components of the body's immune system that provide the ability to regulate inflammation and autoimmunity," stated Dr. James Bianco, President and Chief Executive Officer of TuHURA Biosciences. "With our discovery of DOR expression, and that DOR activation is coupled to mechanisms by which both MDSCs and TAMs contribute to the immunosuppressive phenotype of the tumor microenvironment, we believe that the DOR represents a novel shared target for pharmacologic intervention to overcome resistance to cancer immunotherapies. TuHURA Biosciences is eager to leverage our discoveries around the DOR to develop highly potent and selective DOR inhibitors to create a new class of immune-modulating ADCs by linking a DOR inhibitor to our VISTA inhibiting antibody."

Oral Presentation Details:

Title: Delta Opioid Receptor (DOR) Expression on Myeloid-Derived Suppressor Cells (MDSCs) Represents a Novel Target to Overcome Resistance to Immune Checkpoint Inhibitors (ICIs)
Session: 201. Granulocytes, Monocytes, and Macrophages: New findings in neutropenia and myelopoiesis
Abstract Number: 14322
Presenter: Mike Turner, Ph.D. Vice President Immunology
Date and Time: December 7, 2025, from 5:15 – 5:30 PM ET
Location: W314 – OCC

Poster Presentation Details:

Title: Delta Opioid Receptor (DOR): A Novel Target for Reprogramming Tumor-Associated Macrophage (TAM) Immunosuppressive Phenotype to Overcome Acquired Resistance and Enhance the Effectiveness of Cancer Immunotherapies
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster I
Abstract Number: 2568
Presenter: Krit Ritthipichai, D.V.M., Ph.D., Director of Immunology, TuHURA Biosciences
Date and Time: December 6, 2025, from 5:30 – 7:30 PM ET
Location: West Halls B3-B4 – OCCC

Additionally, The Moffitt Cancer Center, under its collaborative work with TuHURA, will present a poster outlining the pathogenic role of DOR expressing MDSCs in patients with myeloid dysplastic syndrome (MDS). Collectively, these three presentations at ASH highlight the potential of DOR antagonism as a potential effective strategy warranting clinical investigation.

Title: Delta opioid receptor signaling modulates myeloid suppression in Myelodysplastic Syndromes
Session: 636. Myelodysplastic Syndromes: Basic and Translational: Poster II
Abstract Number: 15332
Presenter: Erika Eksioglu, M.D., Department of Immunology, Moffitt Cancer Center
Date and Time: December 7, 2025, from 6:00 – 8:00 PM ET
Location: West Halls B3-B4 – OCCC

About TuHURA Biosciences, Inc.
TuHURA Biosciences, Inc. (Nasdaq: HURA) is a Phase 3 immuno-oncology company developing novel technologies to overcome primary and acquired resistance to cancer immunotherapy, two of the most common reasons cancer immunotherapies fail to work or stop working in the majority of patients with cancer.

TuHURA's lead innate immune agonist, IFx-2.0, is designed to overcome primary resistance to checkpoint inhibitors. TuHURA initiated a single randomized placebo-controlled Phase 3 registration trial of IFx-2.0 administered as an adjunctive therapy to Keytruda^® (pembrolizumab) compared to Keytruda^® plus placebo in first-line treatment for advanced or metastatic Merkel Cell Carcinoma.

In addition to its innate immune agonist product candidates, TuHURA acquired TBS-2025 in its merger with Kineta Inc. on June 30, 2025. TBS-2025 is a VISTA inhibiting mAb asset moving into Phase 2 development in mutNPM1 r/r AML. In addition, TuHURA is leveraging its Delta Opioid Receptor technology to develop first-in-class, bi-specific antibody drug conjugates and antibody peptide conjugates targeting Myeloid Derived Suppressor Cells to inhibit their immune-suppressing effects on the tumor microenvironment to prevent T cell exhaustion and acquired resistance to checkpoint inhibitors and cellular therapies.

For more information, please visit www.tuhurabio.com and connect with TuHURA on Facebook, X, and LinkedIn.

CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS
This press release contains certain "forward-looking statements" within the meaning of, and subject to the safe harbor created by, Section 27A of the Securities Act, Section 21E of the Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These Forward-looking statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and other future conditions. In some cases you can identify these statements by forward-looking words such as "believe," "may," "will," "estimate," "continue," "anticipate," "intend," "could," "should," "would," "project," "plan," "expect," "goal," "seek," "future," "likely" or the negative or plural of these words or similar expressions. Examples of such forward-looking statements include but are not limited to express or implied statements regarding TuHURA's expectations, hopes, beliefs, intentions or strategies regarding the future and include, without limitation, statements regarding TuHURA's Delta Opioid Receptor Technology, its IFx-Hu2.0 product candidate and Phase 3 trial, and its TBS-2025 asset, and any developments or results in connection therewith and the anticipated regulatory pathway and timing of the foregoing development programs, studies and trials. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. You are cautioned that such statements are not guarantees of future performance and that actual results or developments may differ materially from those set forth in these forward-looking statements. Factors that could cause actual results to differ materially from these forward-looking statements are described in detail in our registration statements, reports and other filings with the SEC, which are available on the combined company's website, and at www.sec.gov.

The forward-looking statements and other information contained in this press release are made as of the date hereof, and TuHURA does not undertake any obligation to update publicly or revise any forward-looking statements or information, whether as a result of new information, future events or otherwise, unless so required by applicable securities laws. Nothing herein shall constitute an offer to sell or the solicitation of an offer to buy any securities.

Investor Contact:
Monique Kosse
Gilmartin Group
[email protected]

SOURCE TuHURA Biosciences, Inc.