On April 29, 2025 Nouscom, a clinical-stage biotech company developing next-generation neoantigen-targeted off-the-shelf and personalized cancer immunotherapies, reported complete safety and immunogenicity results from a Phase Ib/II study evaluating NOUS-209 in individuals with Lynch Syndrome (LS) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, NousCom, APR 29, 2025, View Source;utm_medium=rss&utm_campaign=nouscom-presents-positive-final-results-from-completed-phase-ib-ii-study-of-neoantigen-immunotherapy-nous-209-at-aacr-2025-demonstrating-a-highly-potent-and-durable-immune-response-in-lynch-syndrome [SID1234652315]). The study found that NOUS-209 monotherapy was safe, well-tolerated and induced potent, broad and durable immune responses in all LS carriers evaluated.

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LS is a common inherited condition that significantly increases a person’s risk of developing microsatellite instability (MSI)-associated cancers over their lifetime. Managing LS is limited to frequent screenings or elective organ removal surgery. NOUS-209 is an investigational off-the-shelf cancer immunotherapy that targets tumors with mismatch repair deficiency (dMMR) and/or MSI. These tumors produce markers known as frameshift peptide neoantigens (FSPs). NOUS-209 is a pioneering approach to cancer interception comprising two proprietary viral vectors that deliver 209 shared FSP neoantigens and train the immune system to recognize and attack cancerous and pre-cancerous cells before tumors can fully develop.

The completed Phase Ib/II trial evaluated safety and immunogenicity in 45 LS carriers demonstrated;

Favorable Safety Profile: NOUS-209 was well tolerated, with no serious treatment-related adverse events across the entire study population.
Potent and Durable Immunogenicity Profile: Neoantigen-specific T cell responses were reported in 100% of evaluable participants (n=37). Responses were robust, reaching a mean of ~1100 interferon-gamma (IFN-γ) spot forming cells (SFC) per million of Peripheral Blood Mononuclear Cells (PBMCs). Immune responses were durable, with tumor-specific T cells detected after 1 year in >85% of participants (n=33).
Broad, Polyspecific T Cell Response: Immune responses were confirmed against 115 different FSP neoantigens to date, validating the ability of NOUS-209 to elicit broad polyspecific immune responses.
Desired T Cell Phenotype: NOUS-209 induced neoantigen-specific CD8 and CD4 T cells, exhibiting an effector memory phenotype associated with long-lived immunity critical for sustained surveillance and ability to eliminate emerging tumor cells.
Demonstration of Tumor Cell Killing: T cells induced by NOUS-209 were shown to directly kill tumor cells ex vivo, confirming functional anti-cancer activity.
Target Validation in LS-Associated Premalignant and Cancer Lesions: The vast majority of the immunogenic FSP neoantigens were shown to be present in both pre-cancerous as well as cancer lesions from independent cohorts of LS carriers.
These data support the further clinical development of NOUS-209 as a monotherapy in LS carriers. Following positive Type B and C meetings with the US Food and Drug Administration (FDA), Nouscom has a clear path forward for the advancement of NOUS-209 to a potentially registration-enabling Phase 2/3 clinical study for cancer interception in those living with LS.

"Currently, individuals with Lynch Syndrome rely on frequent screenings, such as colonoscopies, to manage their markedly increased risk of developing cancer. These latest data are a step toward a completely new approach – leveraging the immune system for cancer interception," said the study’s principal investigator, Eduardo Vilar-Sanchez, M.D., Ph.D., Professor of Clinical Cancer Prevention at The University of Texas MD Anderson Cancer Center. "NOUS-209 has shown clear evidence that the T cells it activates can persist over time, effectively target and kill tumor cells and develop into memory cells that support long-term immune protection. These findings support NOUS-209’s potential as a cancer interception strategy."

"Nouscom’s proprietary viral vector platform is uniquely positioned to deliver rapid, potent and broad immune activation against a large number of shared neoantigens, with minimal reactogenicity and durable immune responses," said Dr. Elisa Scarselli, Chief Scientific Officer of Nouscom. "These compelling Phase Ib/II data further reinforce our confidence in NOUS-209 monotherapy to safely and effectively prime the immune system to recognize and intercept pre-malignant and cancer lesions before they progress into tumors in LS carriers."

Dr. Marina Udier, Chief Executive Officer of Nouscom, added: "We are enormously pleased with these robust Phase Ib/II data and look to progress toward a potentially registration-enabling Phase 2/3 clinical study for cancer interception in LS. We remain deeply committed to advancing NOUS-209 and bring better solutions for people living with LS who urgently need and deserve a better way to manage their cancer risk."

The study was led by researchers at MD Anderson, in collaboration with the Cancer Prevention Clinical Trials Network and sponsored by the National Cancer Institute (grant # UG1CA242609) of the National Institutes of Health. These data were presented during the Hot Topics in Cancer Prevention session, and the abstract is available on the AACR (Free AACR Whitepaper) website here.