OSE Immunotherapeutics Unveils New Bispecific Technology for Enhanced Cytokine Drugs

OSE Immunotherapeutics SA, based in NANTES, France, revealed on October 17 at 6:00 pm CET, that it will showcase its innovative OSE-CYTOMASK Cis-Demasking cytokine technology at several international conferences. These feature the Festival of Biologics in Basel, Switzerland on October 17, 2024, the 16th Annual Protein & Antibody Engineering Summit (PEGS) in Barcelona, Spain on November 7, 2024, and the Antibody Therapeutics Xchange in Brussels on November 18, 2024. The technology is designed to create a new class of cytokine therapeutics that offer highly active medicines with an improved therapeutic index.

OSE-CYTOMASK employs a novel non-cleavable linker technology to develop regulated and targeted cytokine therapeutics. This innovative approach features two initial preclinical programs centered on anti-PD1 masked cytokines (IL-2, IL-15) for oncology, which include conditional Cis-Demasking and Cis-Potentiation targeting tumor-specific T cells expressing PD1 or other immune targets.

Aurore Morello, Head of Research at OSE Immunotherapeutics, expressed her enthusiasm about presenting the OSE-CYTOMASK technology at prominent scientific conferences. She emphasized that the novel linker technology allows for conditional Cis-Demasking of cytokines through PD1-targeting on tumor-specific T cells without relying on protease-cleavable technology or mutagenesis. This approach mitigates the significant toxicity often associated with cytokines of this class. The promising preclinical efficacy and good tolerance profile observed in the first two drug candidates pave the way for potentially new treatment options in oncology for patients in critical need.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, added that the advancement of these programs highlights the achievements of their research team. He noted that this cutting-edge technology has the potential to maximize the therapeutic benefits of cytokines in oncology by significantly improving the therapeutic index of these drugs. Poirier also mentioned the potential applications of this innovative technology in treating autoimmune and inflammatory diseases.

Immunostimulatory cytokines are powerful drugs used to reactivate the immune system against tumors. However, their narrow therapeutic index, associated with significant peripheral toxicity and limited drug exposure in the tumor microenvironment (TME), poses challenges for their clinical development. Traditional cytokine masking approaches relying on enzyme-cleavable linkers for theoretical demasking activity in the TME have shown limitations due to heterogeneous protease expression in tumors and non-specific protease expression at non-tumor sites, leading to off-tumor cytokine activity.

To address these issues, OSE Immunotherapeutics has engineered a non-cleavable recombinant linker technology that allows specific conditional delivery of cytokine activity only where it is needed based on a targeted Cis-Demasking mechanism independent of protease expression. The OSE-CYTOMASK technology has been initially employed to refine the company's proprietary anti-PD1 BiCKI® platform, enhancing the therapeutic index of highly active cytokines like IL-2 and IL-15. The two preclinical programs with anti-PD1/masked IL-2 and anti-PD1/masked IL-15 have shown robust preclinical efficacy in monotherapy, leading to high anti-tumor response rates and tumor eradication in various models such as orthotopic pancreatic tumor, melanoma, and colon cancer, without peripheral toxicity. This demonstrates a significantly improved therapeutic index for both IL-2 and IL-15 using the OSE-CYTOMASK technology.

The details of the presentations are as follows:
- Festival of Biologics in Basel on October 17, presented by Aurore Morello, Ph.D.: "OSE-Cytomask Technology: Cis-Demasking Cytokine Technology for Targeted Delivery."
- Protein & Antibody Engineering Summit (PEGS) in Barcelona on November 7, presented by Nicolas Poirier, Ph.D.: "OSE-CYTOMASK: Cis-Demasking Cytokine Technology with Non-Cleavable Linker."
- Antibody Therapeutics Xchange in Brussels on November 18, presented by Aurore Morello, Ph.D.: "Addressing Challenges Faced for Optimal Bi-specific and Immunocytokines Engineering."

OSE Immunotherapeutics continues to focus on developing groundbreaking therapies in immuno-oncology and immuno-inflammation, aiming to deliver next-generation treatments to meet critical medical needs.