On December 8, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported that its research on the potential role of the Delta Opioid Receptor (DOR) in controlling the immunosuppressive capabilities of MDSCs was presented in an oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition that took place on Sunday, December 7 in Orlando, FL. The Company presented these updated results, along with a poster presentation highlighting the effects of DOR inhibition on TAMs, another immunosuppressive cellular component critical to the tumorigenic microenvironment.

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In the oral presentation, entitled: Delta Opioid Receptor (DOR) Expression on Myeloid-Derived Suppressor Cells (MDSCs) Represents a Novel Target to Overcome Resistance to Immune Checkpoint Inhibitors (ICIs), Dr. Michael Turner, Vice President Immunology at TuHURA Biosciences presented updated data validating DOR expression on MDSCs and further showing that the pharmacological antagonism of DOR reduced the suppressive activity of MDSCs. MDSCs are a heterogeneous population of immature myeloid cells that contribute to creating an immunosuppressive tumor microenvironment (TME) by suppressing anti-tumor immune responses. The study showed that antagonism of the DOR with a specific inhibitor modulated a variety of direct and indirect MDSC-mediated immunosuppressive factors and reversed T cell suppression, suggesting the DOR may be a novel target to reprogram MDSC induced immunosuppression in the TME.

In the poster, entitled: 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, Dr. Krit Ritthipichai, Director of Immunology at TuHURA Biosciences, presented the results of a study that showed how the DOR is highly expressed in tumor-infiltrating myeloid cells, particularly TAMs, indicating that the TME induces DOR upregulation relative to peripheral macrophages, and that targeting the DOR provides a promising strategy to reprogram suppressive TAMs and MDSCs, alleviate T-cell dysfunction, and potentially overcome resistance to checkpoint blockade and other immunotherapies.

Dr. James Bianco, President and Chief Executive Officer of TuHURA Biosciences, said "Innate immune cells, MDSCs, TAMs, and adaptive regulatory T cells (Tregs) are among the most important cellular components of the body’s immune system that provide the ability to regulate inflammation, autoimmunity and immune tolerance. Our discovery of the expression of the DOR on MDSCs and TAMs, and that its activation is coupled to mechanisms by which these cells contribute to immunosuppression, makes the DOR a compelling target for pharmacologic intervention to overcome acquired resistance to cancer immunotherapy. Data demonstrating that the DOR is also expressed on T regs and controls the expression of FOXP3, a critical immunosuppressive gene, provides a shared mechanism by which endogenous opioids, via the DOR, control the immunosuppressive tone of both innate and adaptive immune responses critical in the pathology associated with cancer and autoimmune disease. TuHURA is the first to demonstrate that this single target shares control of the immune suppressive capabilities of these cells and provides us a unique position to exploit pharmacologic modulation of the DOR to overcome resistance to cancer immunotherapy and the treatment of autoimmune and inflammatory diseases."

"The Company has developed a library of highly selective (>1,200 fold) and potent (<1.0 ng/ml) DOR antagonists and is in position to advance our first-in-class immune modulating bi-functional, bi-specific antibody drug conjugates (ADCs). We anticipate our lead ADC candidate to consist of a DOR inhibitor conjugated to our VISTA inhibiting antibody. TuHURA’s updates at this ASH (Free ASH Whitepaper) meeting demonstrate that elucidating the role of VISTA on macrophages and MDSCs in promoting the progression of myelodysplasia (MDS) to acute leukemia, as well as VISTA’s documented role in being central to how leukemia escapes immune recognition, makes it an ideal candidate to link to a DOR inhibitor. Our ADCs have the potential to not only remove the immunosuppressive tone of the TME but to also checkpoint release resting T cells, allowing them to recognize and kill leukemic cells." Dr. Bianco concluded, "We are excited to be at the forefront of these discoveries and look forward to working on the development of a whole new class of ADCs that could meaningfully change the treatment of cancer."

(Press release, TuHURA Biosciences, DEC 8, 2025, View Source [SID1234661286])