Nouscom: Positive Phase 2 immonotherapy results from metastatic colorectal cancer patients

While immune checkpoint inhibitors (anti-PD-1 +/- anti-CTLA-4) are approved as first line treatment for microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), many patients either don’t respond or develop resistance leading to disease progression, leaving limited treatment options.

• Results from this Phase 2 study of NOUS-209 in combination with pembrolizumab in MSI-H mCRC patients refractory to anti-PD-1 therapy demonstrate clinical activity including objective responses and strong disease control in this difficult-to-treat patient population.
• NOUS-209 further induced robust immune activation in the majority of patients. Retreatment at 6 months induced a strong, durable and polytopic T cell immune response correlating with clinical response.
• NOUS-209 monotherapy is also being developed for cancer interception in Lynch Syndrome (LS) carriers, with a registration-enabling Phase 2/3 study in preparation following positive Type B and C FDA meetings.

Nouscom, a clinical-stage biotech company developing next-generation neoantigen-targeted off-the-shelf and personalized cancer immunotherapies, today announced positive results from a completed Phase 2 trial evaluating NOUS-209 in combination with pembrolizumab for patients with microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC) who are refractory to anti-PD-1 therapy. Results from this Phase 2 trial will be presented in a poster session at the upcoming European Society for Medical Oncology (ESMO) Annual Meeting, taking place in Berlin, Germany, from 17 to 21 October 2025.

Study Highlights

• NOUS-209 is an off-the-shelf viral vector-based immunotherapy targeting frameshift peptides specifically expressed on deficient mismatch repair (dMMR)/MSI-H tumors, thereby harnessing the power of the immune system to recognize and eliminate MSI-H cancer cells.
• Anti-PD-1 therapy is the approved first-line standard of care in dMMR/MSI-H mCRC, but resistance or relapse can develop, requiring the development of new treatment options.
• In this Phase 2 trial, NOUS-209 combined with pembrolizumab was administered to 20 evaluable patients with dMMR/MSI-H mCRC who had progressed on prior anti-PD-1 treatment (77% had received prior single agent anti-PD-1 therapy, 23% received combination therapy with anti-CTLA-4). The median number of prior lines was 2 (1-7).
• The primary endpoint was Objective Response Rate (ORR); secondary endpoints included progression-free survival (PFS) and safety, with immunogenicity as an exploratory endpoint.

Key Results

• ORR was 15% (3 partial responses), with a disease control rate (DCR) of 70% (11 stable disease, 6 progressive disease).
• Median progression-free survival (PFS) was 6.4 months.
• Safety profile remained favorable, with no emerging findings.
• Robust immune activation was detected in 80% of patients.
• Seven patients (32%) were retreated with NOUS-209 at 6 months; among those, 86% remained in stable disease and 14% had a partial response, with the latter demonstrating induction of a strong, durable and polytopic T cell immune response with a desired effector memory phenotype and correlating with clinical response.

“There remains a high unmet need for effective therapies that can overcome anti-PD-1 resistance and provide durable disease control. These data are promising in this difficult-to-treat patient population given the modest clinical benefit of approved options in the same setting,” said Javier Ros, MD PhD, from Vall d'Hebron University Hospital.

“These clinical data are very encouraging. NOUS-209 combined with pembrolizumab has demonstrated meaningful disease control and immune activation in patients who have exhausted anti-PD-1 therapy,” said Dr. Sven Gogov, Chief Medical Officer of Nouscom.

“We are excited by the overall positive clinical dataset emerging from the completed clinical trials of NOUS-209, not only in MSI-H mCRC patients but also the Phase 1b/2 results in Lynch Syndrome carriers that were presented earlier this year at AACR. These results support our commitment to advancing NOUS-209 into a registration-enabling study for cancer interception in Lynch Syndrome carriers,” said Dr. Marina Udier, Chief Executive Officer of Nouscom.

About MSI-H mCRC Refractory to anti-PD-1 Therapy
Microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a biologically distinct subtype of colorectal cancer characterized by mismatch repair deficiency. While anti-PD-1 +/- anti-CTLA4 therapies are approved in the first line treatment setting in this population, over 50% of patients do not respond to initial therapy and many responding patients eventually develop resistance and progress, leaving limited treatment options. There remains a high unmet need for effective therapies that can overcome resistance and provide durable disease control in these patients.

About Lynch Syndrome
Lynch Syndrome (LS) is a common inherited condition that significantly increases a person’s risk of developing cancer over their lifetime, especially colorectal cancer (CRC) (up to 50% risk, compared to 2% for general population), endometrial cancer (up to 50% risk, compared to 1-2% for general population) and urothelial cancer (up to 25% risk, compared to 1-2% for general population)1,2,3,4. LS also elevates the risk of developing other cancers including gastric, ovarian, prostate and pancreatic. LS is caused by inherited mutations in specific genes responsible for repairing DNA, leading to the buildup of harmful genetic errors that can accumulate, triggering development of tumors. Currently, managing LS is limited to frequent screenings - such as colonoscopy to try to catch cancer early, but which will not prevent cancer incidence5 - or elective surgery, which is invasive, expensive and negatively impacts quality of life. As a pioneering approach to cancer interception, Nouscom’s investigational immunotherapy, NOUS-209, is designed to train the immune system to recognize and stop cancer before it develops.

About Cancer Interception
Cancer interception is an innovative approach that aims to stop cancer in its earliest stages, before tumors fully develop and spread. Unlike traditional therapies that target established cancers, interception strategies harness advancements in immuno-oncology that are able to train the immune system to recognize and eliminate precancerous and cancerous cells. This approach is particularly crucial for those with high-risk genetic conditions such as LS who are predisposed to developing microsatellite instability (MSI) -associated cancers.

About NOUS-209
NOUS-209 is an investigational off-the-shelf cancer immunotherapy that targets tumors with mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H). These tumors produce unique markers known as frameshift peptide (FSP) neoantigens, which are unique to cancerous cells and absent in healthy cells. NOUS-209 is comprised of two proprietary viral vectors able to deliver 209 shared FSP neoantigens and train the immune system to recognize and attack cancerous and pre-cancerous cells before tumors can develop.

Phase 1b/2 data (NCT0507886656) demonstrated the safety of NOUS-209 and its ability to stimulate potent immune responses in LS carriers7, supporting its advancement into a potentially registration-enabling Phase 2/3 trial in cancer interception. It is also being studied in a randomized Phase 2 study in combination with pembrolizumab for the first line treatment of advanced dMMR and/or MSI-H mCRC. Data published from the successfully completed Phase 1b trial were published in Science Translational Medicine8.