TuHURA Biosciences Presents Data Demonstrating the Delta Opioid Receptor (DOR) as a New Target in Overcoming Acquired Resistance to Immune Checkpoint Inhibitors at the 57th ASH Annual Meeting and Exposition

Rhea-AI Summary

TuHURA Biosciences (NASDAQ:HURA) presented preclinical data at the ASH meeting on Dec 7–8, 2025 showing the Delta Opioid Receptor (DOR) is expressed on tumor-associated myeloid cells and that DOR inhibition reduced their immunosuppressive activity.

Oral data reported DOR on MDSCs with a DOR antagonist reversing MDSC-mediated T cell suppression. Poster data showed DOR upregulation on tumor-associated macrophages (TAMs) and DOR inhibition reversing TAM-driven T cell suppression. The company described a library of highly selective DOR antagonists and plans a lead ADC combining a DOR inhibitor with a VISTA-blocking antibody.

News Market Reaction

+2.06% 14.4x vol

29 alerts

+2.06% News Effect

-43.8% Trough in 29 hr 17 min

+$2M Valuation Impact

$99M Market Cap

14.4x Rel. Volume

On the day this news was published, HURA gained 2.06%, reflecting a moderate positive market reaction. Argus tracked a trough of -43.8% from its starting point during tracking. Our momentum scanner triggered 29 alerts that day, indicating elevated trading interest and price volatility. This price movement added approximately $2M to the company's valuation, bringing the market cap to $99M at that time. Trading volume was exceptionally heavy at 14.4x the daily average, suggesting very strong buying interest.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

DOR antagonist selectivity: >1,200-fold DOR antagonist potency: <1.0 ng/ml

2 metrics

DOR antagonist selectivity >1,200-fold Selectivity of TuHURA’s Delta Opioid Receptor antagonists

DOR antagonist potency <1.0 ng/ml Potency of TuHURA’s Delta Opioid Receptor antagonists

Market Reality Check

Price: $0.5351 Vol: Volume 82,676 is 0.47x th...

low vol

$0.5351 Last Close

Volume Volume 82,676 is 0.47x the 20-day average of 175,371, indicating subdued trading ahead of this news. low

Technical Shares at $1.94 are trading below the $2.79 200-day moving average and well under the $6.90 52-week high.

Peers on Argus

While HURA was down 2.76%, peers were mixed: IOBT -3.24%, PYXS -2.76%, AVTX -1.4...

While HURA was down 2.76%, peers were mixed: IOBT -3.24%, PYXS -2.76%, AVTX -1.46%, SKYE -1.64%, but ONCY rose 1.23%, pointing to stock-specific rather than sector-wide trading.

Historical Context

5 past events · Latest: Nov 14 (Neutral)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Nov 14	Earnings and update	Neutral	+0.5%	Q3 2025 results, Phase 3 enrollment progress, ASH DOR plans, ATM filing.
Nov 03	Scientific selection	Positive	-0.4%	DOR research selected for ASH oral and poster presentations.
Aug 20	Conference appearance	Neutral	-0.7%	Planned presentation at H.C. Wainwright Global Investment Conference.
Aug 14	Earnings and financing	Positive	+10.9%	Q2 2025 results, Kineta acquisition completion, equity financing and trial plans.
Jul 01	Index inclusion	Positive	+10.8%	Addition to Russell 3000 and Russell 2000 indexes and Phase 3 update.

Pattern Detected

HURA has generally reacted positively to major pipeline and index milestones, with occasional divergence on R&D news headlines.

Recent Company History

Over the last six months, TuHURA reported Q2 and Q3 2025 results while advancing its IFx-2.0 Phase 3 program and integrating Kineta’s VISTA antibody asset. Key milestones included completion of the Kineta acquisition and inclusion in the Russell 3000 and Russell 2000 indexes, both followed by double‑digit percentage gains. Earlier ASH‑related DOR research announcements and conference participation saw modest moves. Today’s detailed ASH data extend the prior DOR story and build on the Kineta‑driven VISTA platform integration.

Regulatory & Risk Context

Active S-3 Shelf · $250,000,000

Shelf Active

Active S-3 Shelf Registration 2025-11-03

$250,000,000 registered capacity

TuHURA has an active mixed Form S-3, filed Nov 3, 2025, registering up to $250,000,000 of securities, including an ATM component of up to $50,000,000. An effective shelf and ATM create flexibility for future capital raises, while concurrent resale registration of 9,321,545 shares enables selling stockholders to monetize existing holdings.

Market Pulse Summary

This announcement details ASH 2025 data showing Delta Opioid Receptor expression on MDSCs, TAMs and ...

Analysis

This announcement details ASH 2025 data showing Delta Opioid Receptor expression on MDSCs, TAMs and Tregs, and supports TuHURA’s strategy to pair DOR antagonists with a VISTA‑targeting antibody in bi‑specific ADCs. Historically, acquisition‑related and index milestones have produced notable stock moves, while some research updates had muted impact. Investors may watch how this DOR–VISTA platform progresses clinically and how it intersects with TuHURA’s effective $250,000,000 shelf and capital planning.

Key Terms

delta opioid receptor, myeloid-derived suppressor cells, tumor-associated macrophages, immune checkpoint inhibitors, +4 more

8 terms

delta opioid receptor medical

"data demonstrating the Delta Opioid Receptor (DOR) as a New Target"

A delta opioid receptor is a protein on the surface of nerve and brain cells that acts like a specialized lock for certain opioid molecules; when the right molecule fits, it changes cell activity and can alter pain perception, mood and other nervous-system functions. Investors care because drugs that target this receptor aim to provide new treatments (for pain, depression or other conditions) with different effectiveness and side-effect risks than existing opioid therapies, affecting clinical, regulatory and commercial outcomes.

myeloid-derived suppressor cells medical

"DOR is expressed on tumor-associated Myeloid-Derived Suppressor Cells (MDSCs)"

Myeloid-derived suppressor cells are a varied group of immature immune cells that act like built-in brakes on the body’s immune response, limiting how strongly immune cells attack infections or tumors. They matter to investors because these cells can affect how well immunotherapies and cancer treatments work, influence clinical trial outcomes, and serve as targets or biomarkers for new drugs, so changes in scientific understanding or trial results can materially impact a company’s prospects.

tumor-associated macrophages medical

"DOR is also expressed on tumor associated macrophages (TAMs)"

Tumor-associated macrophages are immune cells that collect inside and around tumors and can either slow or help cancer grow. Like neighborhood firefighters who sometimes end up helping arsonists, these cells can clear debris and fight disease but may also shelter tumor cells, support blood vessel growth, or blunt treatments. Investors watch them because they are targets for new drugs and can influence a therapy’s effectiveness, development risk, and market value.

immune checkpoint inhibitors medical

"target to Overcome Resistance to Immune Checkpoint Inhibitors (ICIs)"

Drugs that release the immune system’s natural “brakes,” allowing immune cells to recognize and attack cancer cells; imagine taking the safety off a guard dog so it can chase intruders. They matter to investors because they can become high-value treatments with large sales potential, but their commercial success depends on clinical trial results, regulatory approval, competition and side-effect management, which all affect a company’s valuation.

tumor microenvironment medical

"reprogram MDSC induced immunosuppression in the TME."

The tumor microenvironment is the immediate area surrounding a cancer cell, made up of nearby cells, blood vessels, and support structures that influence how the cancer grows and spreads. It functions like a bustling neighborhood that can either help or hinder the tumor’s development. For investors, understanding changes in this environment can signal the effectiveness of treatments and potential shifts in a cancer-related market.

antibody drug conjugates technical

"first-in-class immune modulating bi-functional, bi-specific antibody drug conjugates (ADCs)."

Antibody drug conjugates are targeted medicines that combine an antibody, which seeks out specific markers on diseased cells, with a powerful drug that is released only when the antibody binds its target. Think of it as a guided missile that delivers a toxic payload directly to its target, reducing damage to healthy cells; investors watch them because successful ADCs can offer high-value, niche treatments and drive strong revenue and patent-based protection for developers.

regulatory T cells medical

"adaptive regulatory T cells (Tregs) are among the most important cellular components"

Regulatory T cells are a specialized type of immune cell that act like a brake on the body’s defense system, preventing it from attacking healthy tissue or causing chronic inflammation. They matter to investors because drugs that increase or block these cells can change treatment success and safety in areas such as autoimmune disease, organ transplants, and cancer immunotherapy, affecting clinical trial results, approval chances, and commercial value.

FOXP3 medical

"controls the expression of FOXP3, a critical immunosuppressive gene"

FOXP3 is a gene that produces a protein serving as a master switch for regulatory T cells, the immune system’s brakes that prevent excessive inflammation and autoimmune reactions. Investors care because therapies or diagnostics that target FOXP3 can alter immune behavior and become treatments or biomarkers for autoimmune disease, cancer immunotherapy, or transplant rejection, influencing clinical trial success, regulatory decisions, and commercial value much like a control knob that shifts therapeutic effects.

AI-generated analysis. Not financial advice.

Oral Presentation highlighted new scientific evidence that DOR is expressed on tumor-associated Myeloid-Derived Suppressor Cells (MDSCs), and its inhibition decreases immune suppressing capabilities of MDSCs by downregulating expression of multiple genes associated with MDSC induced immunosuppression

Data presented in the Company's poster demonstrated that the DOR is also expressed on tumor associated macrophages (TAMs) and DOR inhibition appears to reverse TAM mediated T cell suppression with the potential to overcome resistance to checkpoint inhibitor and other cancer immunotherapies

TAMPA, Fla., Dec. 8, 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 (DOR) in controlling the immunosuppressive capabilities of MDSCs was presented in an oral presentation at the 67^th American Society of Hematology (ASH) 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.

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 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."

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 has 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, bi-functional antibody drug 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
Monique@GilmartinIR.com

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SOURCE TuHURA Biosciences, Inc.

FAQ

What did TuHURA (HURA) announce at ASH on Dec 7–8, 2025 about DOR and MDSCs?

TuHURA reported that DOR is expressed on MDSCs and that pharmacologic DOR antagonism reduced MDSC immunosuppressive activity and reversed T cell suppression.

How did TuHURA (HURA) say DOR affects tumor-associated macrophages (TAMs)?

The company presented poster data showing DOR is upregulated on TAMs in the tumor microenvironment and that DOR inhibition appears to reverse TAM-mediated T cell suppression.

What therapeutic approach did TuHURA (HURA) describe involving DOR and VISTA?

TuHURA plans a lead ADC that links a DOR inhibitor to a VISTA-inhibiting antibody to both reprogram myeloid suppression and release checkpoint-inhibited T cells.

Does TuHURA (HURA) have DOR inhibitors ready for development and how selective are they?

The company said it has a library of highly selective DOR antagonists (>1,200-fold selectivity) with potency <1.0 ng/ml ready to support ADC development.

What potential clinical impact did TuHURA (HURA) claim for targeting DOR in cancer immunotherapy?

TuHURA said targeting DOR may reprogram MDSCs and TAMs to overcome acquired resistance to checkpoint inhibitors and improve immunotherapy effectiveness.