Nouscom announced today that it will present complete safety and immunogenicity results from a successful Phase Ib/II trial of NOUS-209 in individuals with Lynch Syndrome (LS) at the upcoming American Academy of Cancer Research (AACR) Annual Meeting in Chicago this April.
The trial, which enrolled 45 LS carriers, demonstrated that NOUS-209 was safe and well-tolerated with no treatment-related serious adverse events. More significantly, immunogenicity analysis revealed neoantigen-specific T cell responses in 100% of evaluable participants (N=37), showing robust, polyfunctional, and durable CD8 and CD4 T cell responses against multiple frameshift peptide (FSP) neoantigens.
A Novel Approach to Cancer Interception
Lynch Syndrome affects approximately 1 in 300 people and significantly increases lifetime cancer risk by up to 80%, particularly for colorectal cancer (up to 50% risk compared to 2% in the general population) and endometrial cancer (up to 50% risk compared to 1-2% in the general population).
Current management options for LS are limited to frequent screenings, which can detect but not prevent cancer, or elective surgeries that are invasive and impact quality of life. NOUS-209 represents a pioneering approach to cancer interception by training the immune system to recognize and eliminate precancerous cells before tumors develop.
"Cancer interception represents a paradigm shift in how we approach high-risk conditions like Lynch Syndrome," said Rick Davis, COO of Nouscom. "Rather than waiting for cancer to develop and then treating it, we're aiming to stop it at its earliest stages."
Mechanism of Action and Therapeutic Potential
NOUS-209 is an off-the-shelf immunotherapy specifically designed to target tumors with mismatch repair deficiency (dMMR) and/or microsatellite instability (MSI). These genetic deficiencies produce unique markers called frameshift peptides (FSPs), which serve as tumor-specific neoantigens.
The immunotherapy utilizes two proprietary viral vectors to deliver 209 unique FSP neoantigens shared across multiple MSI tumor types. Because FSPs are exclusively found in tumors and absent in healthy cells, they are readily recognizable by the immune system, making them ideal targets for immunotherapy.
This approach enables NOUS-209 to potentially treat a broad range of MSI-associated cancers, which are common in Lynch Syndrome patients.
Path Forward to Registration-Enabling Trial
Following positive Type B and C meetings with the U.S. Food and Drug Administration (FDA), Nouscom has established a clear path forward for advancing NOUS-209 to a potentially registration-enabling Phase 2/3 clinical study for cancer interception in people living with Lynch Syndrome.
The oral presentation at AACR, titled "Nous-209 Off-the-Shelf Neoantigen Immunotherapy induces robust neoantigen T cell response with the potential to intercept cancer in Lynch Syndrome carriers," is scheduled for April 29, 2025, at 2:30-4:30 pm CDT in the "Hot Topics in Cancer Prevention" session.
Broader Clinical Development Program
Beyond its application in cancer interception for Lynch Syndrome, NOUS-209 is also being studied in a randomized Phase 2 study in combination with pembrolizumab for the treatment of advanced dMMR and/or MSI metastatic colorectal cancers (mCRC).
Data from the successfully completed Phase 1b trial were published in Science Translational Medicine, further validating the potential of this innovative approach.
About Nouscom
Nouscom is a clinical-stage biotech company developing next-generation neoantigen-targeted off-the-shelf and personalized cancer immunotherapies. The company's proprietary viral vector platform enables broad and durable immune activation by delivering optimized neoantigens that train the immune system to recognize and fight cancer.
In addition to NOUS-209, the company's clinical stage portfolio includes NOUS-PEV, a personalized neoantigen immunotherapy with published data from a successfully completed Phase 1b trial. Nouscom has also out-licensed VAC-85135, an off-the-shelf immunotherapy currently under evaluation in a Phase 1 trial for the treatment of Myeloproliferative Neoplasms sponsored by Janssen Research & Development and Bristol Myers Squibb.
The clinical trial (NCT05078866) was led by researchers at The University of Texas MD Anderson Cancer Center, in collaboration with the Cancer Prevention Clinical Trials Network and sponsored by the National Cancer Institute.
