NOUS-209 / Nouscom - LARVOL DELTA

Safety and Immunogenicity of Re-vaccination with Nous-209: a neoantigen vaccine for cancer interception in Lynch syndrome carriers (ESMO 2026) - No abstract available

Clinical • Tumor-specific neoantigens • Oncology

Colonic Polyp Regression After Nous-209 Cancer Immunotherapy: A Clinical Trial Case Report. (PubMed, J Immunother Precis Oncol) - P1/2 | "Three months after treatment ended, the patient experienced an episode of grade 3 immune-mediated colitis and this improved after infliximab treatment. The clinical and immunologic findings suggest the potential for Nous-209 immunotherapy, in combination with pembrolizumab, to induce regression of both malignant and premalignant colonic lesions. To our knowledge, this is the first report of an immunotherapy combination to reduce premalignant polyps in a patient who does not have Lynch syndrome."

IO biomarker • Journal • Colonic Polyps • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Oncology • Solid Tumor

Nouscom…announced that new data from its Phase 1b/2 trial of NOUS-209 in Lynch Syndrome (LS) carriers have been accepted for an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 (GlobeNewswire) - "It will report the safety and immunogenicity of NOUS-209 re-treatment alongside clinical follow-up extending beyond one year, further reinforcing the strength and durability of the data supporting NOUS-209 as a potential cancer interception immunotherapy for LS carriers....The clinical trial NCT05078866 was a collaborative effort between the National Cancer Institute’s Cancer Prevention Clinical Trials Network (CP-CTNet) and the iCAN-PREVENT consortium at MD Anderson."

P1/2 data • Colorectal Cancer

Nouscom…announced that new data from its Phase 1b/2 trial of NOUS-209 in Lynch Syndrome (LS) carriers have been accepted for an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026, taking place October 23-27 in Madrid, Spain. (The Manila Times)

P1/2 data • Genetic Disorders

Nouscom Receives U.S. FDA Fast Track Designation for NOUS-209, a Novel Immunotherapy for the Prevention of Lynch Syndrome-Associated Cancers (The Manila Times) - "Designation further reinforces Nouscom’s momentum toward initiating a registration-enabling clinical trial of NOUS-209 for cancer interception in LS carriers, following its recent Phase 1b/2 data published in Nature Medicine."

dMMR • Fast track • Colorectal Cancer • Microsatellite Instability • Solid Tumor

Mutations Targeted by Nous-209 Immunotherapy Occur Early in Lynch Syndrome Carriers' Precancer Lesions with Microsatellite Instability. (PubMed, Cancer Prev Res (Phila)) - "Our study shows that MSI and neoantigen accumulation emerge during the evolution of precancerous lesions in LS. These findings support the clinical evaluation of Nous-209, a shared neoantigen vaccine, as an immunoprevention strategy for MSI-driven colorectal carcinogenesis, with important implications for cancer prevention research."

IO biomarker • Journal • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • MLH1 • MSH2 • MSI

Frameshift neoantigen-based vaccine testing in an intra-cecal implantation mouse model of Lynch syndrome [WITHDRAWN] (AACR 2025) - "Indeed, frameshift neoantigen-based vaccines have been developed and are being tested in LS or MSI-H patients in clinical trials (e.g., NOUS-209)...Additional studies are needed to confirm whether this is neoantigen vaccine specific. In summary, this intra-cecal implantation LS model appears suitable for preclinical neoantigen-based vaccine testing and may help elucidate aspects of tumor cell/DNA shedding and distant metastasis."

Preclinical • Tumor-specific neoantigens • Colorectal Cancer • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • MLH1 • MSH2 • MSH6 • MSI • PMS2

Nous-209 off-the-shelf neoantigen immunotherapy induces robust neoantigen T cell response with the potential to intercept cancer in Lynch syndrome carriers (AACR 2025) - P1/2 | "Neoantigen specific immune responses post Nous-209 were observed in 100% of evaluable participants (37/37), with induction of robust T cell immunity reaching a mean of T cell response at peak of ~ 1100 IFN-γ spot forming cells (SFC) per million of PBMC, polyfunctional and long lasting CD8 and CD4 T cell responses broadly recognizing multiple FSPs. The use of peptide binding HLA predictions allowed the precise identification of several immunogenic FSPs, shown to be present in independent datasets of MSI premalignant lesions and cancers in LS carriers.The complete safety and immunogenicity results from this Phase Ib/II trial support the further development of Nous-209 monotherapy, highlighting its potential to efficiently stimulate the immune system and intercept cancer in LS carriers."

IO biomarker • Tumor-specific neoantigens • Microsatellite Instability • Oncology • CD4 • CD8 • IFNG • MSH2 • MSI

Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial. (PubMed, Nat Med) - P1/2 | "Immunogenic FSPs were found in independent datasets of LS MSI colorectal precancers and cancers. These results highlight Nous-209 ability to efficiently stimulate immunity against neoantigens in LS, supporting its development for cancer interception (ClinicalTrials.gov identifier: NCT05078866 )."

IO biomarker • Journal • P1/2 data • Colorectal Cancer • Fatigue • Genetic Disorders • Microsatellite Instability • Oncology • CD4 • CD8 • IFNG • MSI

NOUS-209 off-the-shelf immunotherapy has the potential to hit primary and metachronous colorectal and urothelial cancer in Lynch syndrome. (PubMed, Mol Cancer Ther) - "These findings demonstrated that NOUS-209 FSMs are present in both CRCs and UCs in LS, expanding the therapeutic potential of NOUS-209 beyond CRC. Moreover, the emergence of novel targetable FSMs in metachronous tumors suggests that NOUS-209 immunotherapy may be effective in the prevention of both primary and metachronous LS-associated cancers."

IO biomarker • Journal • Colorectal Cancer • Genetic Disorders • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • MSI

Nouscom Presents New Positive Phase 1/2b data of NOUS-209 at SITC 2025, Supporting Plans to Initiate Registration-Enabling Study for Cancer Interception in Lynch Syndrome Carriers (GlobeNewswire) - "First Clinical Evidence of Cancer Interception: While 4.7% of LS participants had advanced adenomas at baseline (which were removed as part of standard of care), no new advanced adenomas were detected after treatment despite an expected annual incidence of around 4%, providing initial evidence of NOUS-209’s cancer preventive efficacy in LS carriers."

P1/2 data • Oncology

Final ph1b/2 results for Nous-209 monotherapy in Lynch syndrome carriers: Annual revaccination boosts T cell immunity informing future cancer interception strategies (SITC 2025) - P1/2 | "Advanced adenomas were detected in 4.65% of patients at baseline, but none post Nous-209.Conclusions This trial demonstrates that annual revaccination with Nous-209 is safe, and effectively boosts neoantigen-specific T cell responses, supporting the importance of annual revaccination in the future clinical development of NOUS-209 for cancer interception in LS.Acknowledgements The authors acknowledge DMACC for its coordinating and support functions (U24CA242637). Support: NCI/NIH UG1CA242609, NouscomTrial Registration Clinical trial information: NCT05078866."

IO biomarker • Late-breaking abstract • Monotherapy • P1/2 data • Microsatellite Instability • Oncology • IFNG • MSH2 • MSI

NOUS-209 off-the-shelf immunotherapy enables broad targeting of primary and metachronous tumors in Lynch Syndrome (SITC 2025) - "Analysis of B2M revealed loss in a subset of tumors, more frequently observed in advanced tumors than in early ones, suggesting that B2M loss is a late event and that vaccination at early stage before such escape mechanism are established might ensure optimal effectiveness.Conclusions Our results demonstrate the presence of NOUS-209 FSMs in both CRCs and UCs in LS, highlighting the broader therapeutic applicability beyond colorectal cancer. Furthermore, the emergence of new targetable FSMs in metachronous tumors supports the potential of NOUS-209 immunotherapy as a preventive strategy for both primary and recurrent LS-associated malignancies."

IO biomarker • Colorectal Cancer • Genito-urinary Cancer • Microsatellite Instability • Oncology • Solid Tumor • Urothelial Cancer • B2M • MSI

Nous-209 immunotherapy with pembrolizumab for microsatellite instability high (MSI-H) metastatic colorectal cancer, refractory to anti-PD-1: Phase II trial results (ESMO 2025) - P1/2 | "Among those, 86% remained in SD and 14% had PR, the PR demonstrating induction of a strong and polytopic T effector memory phenotype cell immune response corresponding to clinical response. Conclusions Overall, these data demonstrated a 15% ORR, 70% DCR and mPFS of 6.4 months in αPD-1 refractory MSI-H mCRC patients treated with Nous209 plus pembrolizumab."

Metastases • MSI-H • P2 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Nouscom to Present New Positive Phase 1b/2 Clinical and Translational Data on NOUS-209 Immunogenicity and Cancer Interception Potential in Lynch Syndrome Carriers at SITC 2025 (GlobeNewswire)

P1/2 data • Colorectal Cancer • Oncology

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2025 ➔ Sep 2026

IO biomarker • Trial completion date • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI

Nouscom Presents Positive Phase 2 Results of NOUS-209 Immunotherapy Combined with Pembrolizumab in MSI-H Metastatic Colorectal Cancer Patients Refractory to Anti-PD-1 Therapy, at ESMO 2025 (GlobeNewswire) - "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....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."

dMMR • MSI-H • P2 data • Colorectal Cancer • Microsatellite Instability

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Sep 2025

IO biomarker • Trial completion date • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=44 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2025 ➔ Jul 2026

IO biomarker • Trial completion date • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI

KEYNOTE-E58: Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors (clinicaltrials.gov) - P1/2 | N=115 | Active, not recruiting | Sponsor: Nouscom SRL | Trial primary completion date: Apr 2025 ➔ Oct 2026

Trial primary completion date • Colorectal Cancer • Gastric Cancer • Solid Tumor • MSI

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 Carriers (GlobeNewswire) - P1b/2 | N=44 | NCT05078866 | "The completed Phase Ib/II trial evaluated safety and immunogenicity in 45 LS carriers demonstrated; (i) Favorable Safety Profile: NOUS-209 was well tolerated, with no serious treatment-related adverse events across the entire study population; (ii) 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); (iii) 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..."

P1/2 data • Colorectal Cancer • Microsatellite Instability • Oncology

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=44 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI

Nouscom to Present Final Results from Successful Phase Ib/II Trial of NOUS-209 in People Living with Lynch Syndrome, Demonstrating Powerful Potential to Intercept Cancer in its Earliest Stages of Development (GlobeNewswire) - P1b/2 | N=60 | NCT05078866 | "NOUS-209 was safe and well tolerated, with no treatment-related serious adverse events reported; Immunogenicity analysis showed neoantigen-specific T cell responses in 100% of evaluable participants (N=37); NOUS-209 induced robust, polyfunctional and durable CD8 and CD4 T cell responses against multiple frameshift peptide (FSP) neoantigens; Data support the further clinical development of NOUS-209 monotherapy, highlighting its potential to efficiently stimulate the immune system to intercept cancer in LS carriers."

P1/2 data • Colorectal Cancer • Oncology

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Recruiting | Trial primary completion date: Jul 2025 ➔ Mar 2025

Enrollment open • Trial primary completion date • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI

Endometrial cancer, a therapeutic vaccine under study [Google translation] (ANSA) - "The research has identified, in a group of 35 women with advanced endometrial cancer treated at the Policlinico, a series of shared tumor neo-antigens (over 160) that could become targets for the experimental vaccine Nous-209...'The patients all have the molecular defect of mismatch repair (Mmrd), assessed with immunohistochemistry. These neo-antigens, anomalous proteins resulting from accumulated genetic defects, are not present in normal cells, but only in tumor cells and can act as a target for the specific vaccine.'....'Exploiting to our advantage a molecular defect that is common to several tumors, and having demonstrated that the defects present in colon or stomach cancer are also identifiable in patients with endometrial cancer, allows us to extend the use of this vaccine to women with endometrial cancer, which will be tested in an upcoming phase I trial.'"

New P1 trial • Endometrial Cancer