Odyssey Therapeutics Announces Publication Highlighting Differentiated Therapeutic Potential of TNFR2 Agonism

A single dose increased a tissue-directed regulatory T-cell subset in mice from 22% to 66%, an effect not observed with an IL-2 mutein.

Rhea-AI Summary

Odyssey Therapeutics (ODTX) announced publication of preclinical research examining TNFR2 activation as an approach to controlling autoimmune inflammation through regulatory immune cells.

The study in The Journal of Immunology examined regulatory T cells, which help control inflammation. A single dose of a TNFR2 activator increased a tissue-directed subset among lung regulatory T cells in mice from 22% to 66%; an IL-2 mutein did not produce this effect. Treatment also reduced disease severity in mouse models of skin inflammation and experimental autoimmune encephalomyelitis. Human-cell experiments showed preserved regulatory-cell stability and increased markers of tissue adaptation, including in cells from lupus patients. Odyssey expects its investigational TNFR2 agonist, OD-003, to complete studies supporting an application to begin human testing in Q1 2027.

Positive

• Minor pointTNFR2 activation increased a tissue-directed subset among mouse lung regulatory T cells from 22% to 66%, unlike an IL-2 mutein.
• Minor pointPreclinical treatment reduced disease severity in mouse models of skin inflammation and experimental autoimmune encephalomyelitis.
• Minor pointHuman regulatory T cells retained a genetic marker of lineage stability and produced less inflammatory IFN-γ under inflammatory challenge.
• Minor pointHuman-cell experiments increased tissue-adaptation and immune-regulation markers, including in cells from systemic lupus erythematosus patients.
• Minor point. Forward-looking: it has not happened yet and may not happen.OD-003 is advancing through studies supporting human testing; Odyssey expects completion in Q1 2027.

Negative

• None.

Key Figures

PD-1+BATF+ lung Tregs: 22% to 66% IND-enabling study completion: Q1 2027

PD-1+BATF+ lung Tregs

22% to 66%

After a single dose in mice; the effect was not observed with an IL-2 mutein

IND-enabling study completion

Q1 2027

Expected completion for OD-003

Key Terms

tnfr2 agonism, single-cell analyses, regulatory t cells, ind-enabling studies, +2 more

6 terms

tnfr2 agonism medical

"TNFR2 agonism increases tissue and effector Treg cells"

TNFR2 agonism is the stimulation or activation of the tumor necrosis factor receptor 2 (TNFR2) on cell surfaces by a drug or biologic that binds the receptor and triggers its signaling pathways. Activating TNFR2 can change cell behavior—commonly promoting survival, proliferation, or regulatory functions in certain immune and non-immune cells—depending on which cell types express the receptor and the biological context. The effects of TNFR2 agonists vary by dose, cell type, and disease setting, so agonism describes the mechanism of receptor activation rather than a specific clinical outcome.

single-cell analyses technical

"used single-cell analyses to investigate how activation of tumor necrosis factor receptor 2"

Single-cell analyses are laboratory methods that measure genes, proteins or other features in individual cells rather than averaging results across many cells. Like listening to each musician in an orchestra instead of the whole ensemble at once, this reveals hidden differences and rare cell types that can change how diseases are understood, how drugs are targeted, and how likely a therapy or diagnostic is to succeed — information investors use to judge scientific risk and potential market value.

regulatory t cells medical

"influences regulatory T cells (Tregs), which play a critical role in controlling inflammation"

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.

ind-enabling studies regulatory

"OD-003 is advancing through IND-enabling studies"

Ind-enabling studies are early research efforts that test whether a new drug or treatment is safe and effective enough to move forward in development. They are like preliminary tests to ensure a product works as intended before investing more resources into large-scale trials. For investors, these studies are important because successful results can signal potential progress toward bringing a new product to market, impacting its future value.

foxp3 cns2 region technical

"maintained demethylation of the FOXP3 CNS2 region"

FOXP3 CNS2 region is a specific non‑coding DNA segment within the FOXP3 gene locus, known as Conserved Noncoding Sequence 2, that helps control whether the FOXP3 gene is turned on stably in regulatory T cells. It does not encode protein but contains regulatory elements and DNA methylation sites that influence FOXP3 expression and the long‑term identity and function of those immune cells.

ifn-γ medical

"they produced less IFN-γ, a proinflammatory cytokine"

IFN-γ (interferon‑gamma) is a protein released by immune cells that acts like a traffic cop for the immune system, directing and activating other cells to fight infections and tumors and promoting local inflammation. Investors care because IFN‑γ levels or drugs that change its activity can signal whether an immune therapy is working, affect safety and side effects, guide patient selection for trials, and influence the commercial and regulatory prospects of related treatments and diagnostics.

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“Cutting Edge” article demonstrates that compared with IL-2, TNFR2 agonism promotes tissue-directed regulatory T-cell differentiation and lineage stability, as well as reduces autoimmune inflammation in preclinical models

Company’s investigational TNFR2 agonist, OD-003, expected to complete IND-enabling studies in the first quarter of 2027

BOSTON, Nov. 10, 2026 (GLOBE NEWSWIRE) -- Odyssey Therapeutics, Inc. (Nasdaq: ODTX) (“Odyssey” or the “Company”), a clinical-stage biopharmaceutical company seeking to transform the standard of care for patients suffering from autoimmune and inflammatory diseases by developing medicines that precisely target disease pathology, today announced the publication of a research paper titled, “TNFR2 agonism increases tissue and effector Treg cells” in The Journal of Immunology. The manuscript was selected by the editors as a “Cutting Edge” article, highlighting the scientific significance of the findings.

The research, conducted in collaboration with investigators at the University Medical Center Mainz, used single-cell analyses to investigate how activation of tumor necrosis factor receptor 2 (TNFR2) influences regulatory T cells (Tregs), which play a critical role in controlling inflammation. The findings demonstrate that TNFR2 agonism expands Tregs and promotes their differentiation into specialized cells with tissue-homing potential and stability under inflammatory conditions. In mouse studies, TNFR2 agonism increased tissue-associated Treg populations and reduced disease severity in models of autoimmune inflammation. Consistent with these findings, experiments using human Tregs demonstrated that TNFR2 agonism promotes the expression of genes associated with tissue homing and suppressive function while preserving Treg lineage stability.

“A key challenge in harnessing Tregs therapeutically is directing their differentiation into stable populations capable of controlling inflammation in affected tissues,” said Gary D. Glick, Ph.D., founder and chief executive officer of Odyssey Therapeutics. “These findings demonstrate that TNFR2 agonism promotes the expansion of tissue-competent Tregs while preserving phenotype stability and enhancing immuno-suppressive ability. Together with evidence of reduced disease severity in preclinical models, this research strengthens the therapeutic rationale for OD-003, our TNFR2 agonist, as an investigational treatment for autoimmune and inflammatory diseases and supports the potential superiority of this approach to IL-2-based therapies.”

Summary of key findings

The findings demonstrate that TNFR2 agonism:

• Drives tissue-directed Treg differentiation. A single dose tripled the proportion of PD-1+BATF+ Tregs among lung Tregs in mice (22% to 66%), an effect not observed with an IL-2 mutein.
• Reduces autoimmune inflammation in preclinical models. Treatment increased tissue Treg populations and reduced disease severity in models of skin inflammation and experimental autoimmune encephalomyelitis.
• Preserves Treg lineage stability. Human Tregs expanded with a TNFR2 agonist maintained demethylation of the FOXP3 CNS2 region, an epigenetic hallmark of Treg lineage stability. Functionally, they produced less IFN-γ, a proinflammatory cytokine, when challenged with inflammatory signals, supporting their ability to retain regulatory characteristics under inflammatory conditions.
• Promotes tissue-like differentiation in human Tregs, including those from patients with systemic lupus erythematosus. In vitro studies showed increased expression of markers associated with tissue adaptation and immune regulation, supporting the translational relevance of TNFR2 agonism.

Collectively, these findings highlight the therapeutic potential of TNFR2 agonism to promote stable, tissue-directed Treg populations for the treatment of autoimmune and inflammatory diseases and support the development of OD-003, Odyssey’s investigational TNFR2 agonist. OD-003 is advancing through IND-enabling studies, with completion expected in the first quarter of 2027.

About Odyssey Therapeutics

Odyssey Therapeutics is a clinical-stage biopharmaceutical company seeking to transform the standard of care for patients suffering from autoimmune and inflammatory diseases by developing medicines that are designed to precisely target disease pathology. Since its founding in 2021, Odyssey has built a portfolio of internally discovered and developed medicines with its first program advancing through multiple clinical milestones. Odyssey’s portfolio leverages the scientific expertise of its team of experienced drug hunters and a comprehensive suite of tools to efficiently advance product candidates that the Company believes have the potential to induce deep and durable remission for patients across several inflammatory diseases with unmet need.

For more information, please visit www.odysseytx.com and follow Odyssey on LinkedIn or X.

Forward-looking statements

This press release includes certain disclosures that contain “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the interpretation and potential implications of published preclinical and human cell research on TNFR2 agonism; the potential of TNFR2 agonism to promote regulatory T-cell expansion, tissue-directed differentiation, and stability; the potential translation of these findings to human disease; the therapeutic potential of TNFR2 agonism for autoimmune and inflammatory diseases; and the development, potential efficacy and anticipated benefits of OD-003, including the expected timing of completion of IND-enabling activities.

Forward-looking statements may be identified by words such as “anticipate,” “believe,” “could,” “expect,” “intend,” “goal,” “may,” “plan,” “potential,” “will,” “would” and variations of these words or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements reflect Odyssey’s current expectations and involve risks and uncertainties that could cause actual results to differ materially. These include the inherent limitations of preclinical and in vitro research; uncertainty regarding the translation of preclinical findings to clinical outcomes in humans; the possibility that OD-003 may not demonstrate the anticipated safety, efficacy or biological activity in future clinical trials; risks associated with completing IND-enabling activities and advancing OD-003 into clinical development; clinical, regulatory, competitive and third-party risks; and other factors described under “Risk Factors” in Odyssey’s most recent Form 10-Q and other SEC filings. Odyssey undertakes no obligation to update these statements except as required by law.

Contact

Benjamin Navon
Senior Director, Communications
(857) 431-8785

For investors
investors@odysseytx.com

For media
media@odysseytx.com

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Odyssey Therapeutics' TNFR2 research show?

TNFR2 activation promoted tissue-directed regulatory T cells and reduced disease severity in preclinical models. A single dose increased a tissue-directed subset among mouse lung regulatory T cells from 22% to 66%, an effect not observed with an IL-2 mutein. Human-cell experiments also showed preserved regulatory-cell stability.

When does Odyssey Therapeutics expect OD-003 to complete IND-enabling studies?

Odyssey expects OD-003 to complete IND-enabling studies, which support an application to begin human testing, in the first quarter of 2027. The investigational TNFR2 agonist is currently advancing through those studies.