Nouscom: Patient enrollment of study for metastatic colorectal cancer completed

Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized neoantigen cancer immunotherapies, announces the completion of patient enrollment of 69 patients in a randomized Phase 2 study. This trial evaluates its lead asset, NOUS-209 in combination with pembrolizumab versus pembrolizumab alone in first-line (1L) Deficient Mismatch Repair/Microsatellite Instable (dMMR/MSI) unresectable and metastatic colorectal cancer (mCRC) patients. The efficacy readout for the primary endpoint - Objective Response Rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST1.1) for NOUS-209 combined with pembrolizumab versus pembrolizumab alone – is anticipated in mid-2025.

NOUS-209 is an off-the-shelf immunotherapy encoding 209 neoantigens that are shared across both sporadic and hereditary MSI tumors. The immunotherapy is designed to activate the immune system to generate CD8 and CD4 T cell responses by targeting MSI tumor-specific neoantigens that are created by defective DNA mismatch repair genes (dMMR).

Data published from the successfully completed Phase 1b trial of NOUS-209 plus pembrolizumab in first and second line dMMR/MSI gastrointestinal (GI) tumors demonstrated a clean safety profile with encouraging results, including the strong and long-lasting induction of CD8 and CD4 T cells in 90% of patients. Expansion of intratumoral T cells was shown post NOUS-209 immunotherapy in patients who experienced deep and durable clinical responses, with evidence that neoantigen-specific CD8 T cells induced by NOUS-209 successfully traffic and infiltrate the tumor, correlating with its mechanism of action.¹

These findings, together with new Phase 1b/2 immunogenicity and translational data evaluating NOUS-209 monotherapy in Lynch Syndrome (LS) carriers – presented recently at the Society of Immunotherapy in Cancer (SITC 2024) Meeting² – highlight the unique potential of NOUS-209 both to intercept pre-malignant lesions at the earliest stages of disease development and to treat advanced MSI tumors.

Dr. Marina Udier, CEO of Nouscom said: “The completion of enrollment of our randomized multi-country Phase 2 trial in MSI metastatic mCRC patients is a major milestone for Nouscom. With important data readouts expected in 2025, we are getting closer to answering the key question of whether NOUS-209 immunotherapy meaningfully improves clinical efficacy above and beyond the current standard of care in MSI mCRC. These data will also inform our strategy to investigate the broader potential of NOUS-209 in other MSI cancers that present the same set of neoantigens.

“The next 12 months will be an exciting time for Nouscom as we anticipate key data from this and the ongoing Phase 1b/2 trial in Lynch Syndrome carriers and continue discussions with regulators regarding the further clinical development of NOUS-209, including registrational studies.”

Dr. Sven Gogov, Chief Medical Officer of Nouscom, added: “Colorectal cancer continues to be a leading cause of death, highlighting a clear unmet medical need. This trial, taken with the positive data from our ongoing Phase 1b/2 trial in Lynch Syndrome carriers, continues to support the transformative potential of NOUS-209 immunotherapy from the interception of cancer at the pre-malignant stage through to treating advanced metastatic disease. We are grateful to the patients, their families, the investigators and trial site personnel who have made this trial possible.”

The Phase 2 randomized clinical trial (NCT04041310) is being conducted in multiple centers across the US and Europe. The trial includes two patient cohorts: a 2:1 randomized cohort of previously untreated 1L MSI mCRC patients receiving NOUS-209 plus pembrolizumab versus pembrolizumab alone; and a single-arm cohort of MSI mCRC patients who have become refractory to prior anti-PD1 and other therapies, receiving NOUS-209 plus pembrolizumab.

References

1. D’Alise, M. et al. Adenoviral Based-Vaccine Promotes Neoantigen Specific CD8+ T Cell Stemness And Tumor Rejection, Science Translational Medicine (2022); 14, 657
2. Vilar E, Willis J, D’Alise M, et al. 638 Nous-209 vaccine induces shared neoantigen immunogenicity for cancer interception in healthy lynch syndrome carriers: results from phase Ib/II trial, Journal for ImmunoTherapy of Cancer 2024;12: doi: 10.1136/jitc-2024-SITC2024.0638

About MSI Tumors/ MSI metastatic CRC
Microsatellite instable (MSI) tumors are a subset of cancers characterized by high mutation rates within short, repetitive DNA sequences called microsatellites, arising from defects in the DNA mismatch repair (MMR) system. When the MMR system is deficient (dMMR), errors in DNA replication accumulate, leading to MSI tumors. This instability is particularly significant in colorectal cancer (CRC), where MSI metastatic CRC represents a distinct subtype associated with increased sensitivity to certain immunotherapies. MSI tumors account for approximately 15% of all CRC and 4-5% of all metastatic CRC cases, as reported in a 2015 New England Journal of Medicine study and supported by subsequent research. MSI is also observed in other cancers, most frequently in endometrial and gastric cancers.

About Lynch Syndrome
Lynch Syndrome (LS) is a common hereditary condition that significantly increases the risk of colorectal, endometrial, and gastric cancers. Caused by mutations in DNA mismatch repair genes, LS leads to MSI tumors. Affecting about one in 300 people (Win et al 2017, Cancer Epidemiol Biomarkers Prev), it is estimated that nearly one million individuals in the US have LS, though it remains vastly underdiagnosed due to a lack of approved treatment options. LS carriers face a 50-80% lifetime risk of colorectal cancer and a 40-60% risk of endometrial cancer, along with the burden of frequent invasive surveillance and prophylactic surgery.