NOUS-209 / Nouscom - LARVOL DELTA

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

Frameshift neoantigen-based vaccine testing in an intra-cecal implantation mouse model of Lynch syndrome [WITHDRAWN] (AACR 2025) - "Indeed, frameshift neoantigen-based vaccines have been developed and are being tested in LS or MSI-H patients in clinical trials (e.g.,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

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

NOUSCOM APPOINTS SEASONED EXECUTIVE ECKHARD NIEMEIER AS CHIEF BUSINESS OFFICER (Nouscom Press Release) - "'The next 12 months will be an exciting time for Nouscom as we anticipate key data readouts from clinical trials with our lead asset, NOUS-209, in dMMR/MSI metastatic CRC a in Lynch Syndrome carriers.'....NOUS-PEV, a personalized cancer immunotherapy, is expected to enter randomized Phase 2 trials in indications with high unmet medical need during 2025."

Clinical data • Colorectal Cancer • Microsatellite Instability

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer. (PubMed, NPJ Precis Oncol) - "A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored."

Journal • Mismatch repair • Endometrial Cancer • Oncology • Solid Tumor • MLH1

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 | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2026 ➔ Nov 2026

Enrollment closed • Trial completion date • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • MSI

Nouscom Completes Patient Enrollment of Randomized Phase 2 Study Evaluating NOUS-209, an Off-the-Shelf Neoantigen Immunotherapy, in dMMR/MSI Metastatic Colorectal Cancer (GlobeNewswire) - "Nouscom...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."

Enrollment closed • P2 data • Colorectal Cancer • Microsatellite Instability

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

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

Nous-209 vaccine induces shared neoantigen immunogenicity for cancer interception in healthy lynch syndrome carriers: results from phase Ib/II trial (SITC 2024) - P1/2 | "Consent The data in this abstract is from a clinical trial where written informed consent was obtained from the patient for publication of this abstract. A copy of the written consent is available for review by the Editor of this journal."

Clinical • P1/2 data • Tumor-specific neoantigens • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • IFNG • MSH2 • MSI

Nouscom’s Off-the-Shelf Neoantigen Immunotherapy, NOUS-209, Continues to Elicit Potent and Durable Immune Responses in Lynch Syndrome Carriers Highlighting its Potential to ‘Intercept’ Cancer (GlobeNewswire) - "Nouscom...announces further promising data from the fully enrolled Phase 1b/2 study evaluating NOUS-209 for its potential to ‘intercept’ cancer in Lynch Syndrome (LS) carriers...The new data will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, TX, USA on Saturday 9th November 2024...NOUS-209 monotherapy continued to be safe, well tolerated and to generate potent immunogenic CD4 and CD8 T cell responses in all 23 participants. T cell responses were shown to be potent, broad and durable against multiple neoantigens encoded within NOUS-209...'Primary data read-outs from both the randomized Phase 2 trial in MSI mCRC and the Phase 1b/2 trial in LS are expected by mid-2025. We are excited to plan the future clinical development for NOUS-209 including a path towards registration.'"

P1/2 data • P2 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Nouscom to Present Updated Positive Data on NOUS-209’s Potential to ‘Intercept’ Cancer in Lynch Syndrome Carriers at SITC 2024 (GlobeNewswire) - "Nouscom...announces that updated safety data, as well as compelling immunogenicity and durability of T cell response from its Phase 1b/2 study evaluating NOUS-209 in Lynch Syndrome carriers will be presented at the 39th Society for Immunotherapy of Cancer (SITC) 2024 annual meeting (6th - 10th November 2024, Houston, TX, USA)."

P1 data • Genetic Disorders

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Genetic Disorders • Oncology • BRAF • MLH1 • MSH2 • MSH6 • MSI

Development of a Potency Assay for Nous-209, a Multivalent Neoantigens-Based Genetic Cancer Vaccine. (PubMed, Vaccines (Basel)) - "Results showcase the assay's robustness and biological relevance, as it effectively detects potency loss in one component of the mixture comparably to in vivo immunogenicity testing. This report details the assay's setup and validation, offering valuable insights for the clinical development of similar genetic vaccines, particularly those encoding synthetic polypeptides."

Journal • Tumor-specific neoantigens • Oncology

Angelini Ventures invests into extended €75.8 million ($82 million) Series C financing round for Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized cancer vaccines (GlobeNewswire) - "Angelini Ventures...is pleased to announce its participation in an extension of the Series C financing round for Nouscom...Angelini Ventures’ investment of €7 million brings the total raised by Nouscom, in its oversubscribed Series C round – first announced in November 2023 – to €75.8 million (approx. $82 million)....Readout from its ongoing randomized Phase 2 clinical trial for NOUS-209, an off-the-shelf cancer vaccine for the treatment of Mismatch Repair/Microsatellite Instable (dMMR/MSI) Metastatic Colorectal Cancer (mCRC)....Phase 1b study completion for NOUS-PEV...in combination with a checkpoint inhibitor in patients with advanced melanoma and entry into randomized Phase 2 trials in indications with high unmet medical needs."

Financing • Trial status • Colorectal Cancer • Melanoma • Microsatellite Instability

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | N=45 ➔ 60 | Trial completion date: Jul 2025 ➔ Mar 2025 | Trial primary completion date: Jul 2025 ➔ Mar 2025

Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Oncology • BRAF • MLH1 • MSH2 • MSH6 • MSI

Nouscom Raises €67.5 million ($72 million) in Oversubscribed Series C Financing Round (GlobeNewswire) - "Nouscom...announced the completion of its oversubscribed Series C equity financing raising €67.5 million ($72 million) from a syndicate of renowned international healthcare investors....The proceeds will be used to continue advancing and expanding Nouscom’s wholly owned clinical pipeline...Readout from Nouscom’s ongoing randomized Phase 2 clinical trial for NOUS-209, an off-the-shelf vaccine targeting 209 shared neoantigens, in combination with pembrolizumab for the treatment of Mismatch Repair/Microsatellite Instable (dMMR/MSI) Metastatic Colorectal Cancer (mCRC). Final readout from the ongoing Phase 1b study and advancement of NOUS-209 monotherapy in Lynch Syndrome (LS) carriers investigating the potential to intercept, prevent or delay cancer before it occurs....Completion of a Phase 1b study evaluating NOUS-PEV, a personalized cancer immunotherapy, in combination with a checkpoint inhibitor in patients with advanced melanoma..."

Financing • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

Nous-209 genetic vaccine encoding shared cancer neoantigens is safe and elicits robust immune response in healthy Lynch syndrome carriers: interim results from Phase 1 cancer interception trial (SITC 2023) - P1/2 | "1 A phase I trial (NCT04041310) combining the Nous-209 vaccine with pembrolizumab anti-PD-1 antibody has been recently completed in metastatic colorectal, gastric and gastro-esophageal cancer patients showing excellent safety, immunogenicity, and promising signs of clinical efficacy. Deconvolution of T cell responses against predicted CD8 epitopes included in the FSPs pools showed multiple positive responses, confirming the optimal breadth of immune responses. Conclusions Nous-209 is safe, well tolerated, and elicits potent and broad immune response in both LS carriers previvors and survivors, supporting Nous-209 development as a compelling approach for LS cancer interception."

Clinical • IO biomarker • Late-breaking abstract • P1 data • Tumor-specific neoantigens • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CD4 • CD8 • IFNG • MSI

Results of phase I-II bridging study for Nous-209, a neoantigen cancer immunotherapy, in combination with pembrolizumab as first line treatment in patients with advanced dMMR/MSI-h colorectal cancer. (ASCO 2023) - P1/2 | "The combination of Nous-209 and pembrolizumab is safe, well tolerated and shows encouraging clinical efficacy in patients with treatment-naive dMMR/MSI-H mCRC eligible for anti-PD-1 therapy. The study is ongoing and expanding to Phase II randomization with a new accelerated Nous-209 vaccination schedule. Clinical trial information: NCT04041310."

Clinical • Combination therapy • Metastases • P1/2 data • Tumor-specific neoantigens • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Microsatellite Instability • Oncology • Solid Tumor • MSI

Neoantigen Based Therapeutic Cancer Vaccines: Rationale, Practice and Perspectives in Endometrial Cancer (EACR 2023) - P1/2 | "FSPs were compared to the the previously validated pool of nAgs included in the Nous-209 vaccine at present under evaluation in metastatic MSI solid tumours by Nouscom® (NCT04041310).Results and DiscussionsOf the 35 patients with dMMR, 4 showed an absence of protein expression for hMLH1, 20 for hMLH1/PMS2, 1 for hMSH2/hMSH6, 2 for hMSH6, 7 for PMS2, and 1 for hMSH2 alone...Moreover, samples of our series that showed loss of expression of hMLH1 or hMLH1/PMS2 showed a higher number of FSPs (21 FSPs). Several potential indels leading to FSPs have been reported as well as the identification of a molecular-defect-based behaviour in nAgs enrichment and demonstration of the feasibility of the proteogenomic approach in nAgs prediction and targeting for immunotherapy.ConclusionnAgs have a special value combined as biomarker-driven therapy to novel drug combinations resulting in a novel therapeutic approach that could remodel the management of malignant gynecological..."

IO biomarker • Tumor-specific neoantigens • Endometrial Cancer • Gynecologic Cancers • Microsatellite Instability • Oncology • Solid Tumor • MLH1 • MSH2 • MSH6 • MSI • PMS2 • TP53

Nouscom Announces Clinical Trial Collaboration and Supply Agreement with MSD to Evaluate NOUS-209 in combination with KEYTRUDA (pembrolizumab) in a Phase 2 Randomized Trials in dMMR/MSI-High Metastatic Colorectal Cancer (PRNewswire) - "Nouscom...announced that it has entered into a clinical trial collaboration and supply agreement with MSD...to evaluate Nouscom's wholly-owned lead candidate, NOUS-209, in combination with MSD's anti-PD-1 therapy KEYTRUDA^® (pembrolizumab) versus KEYTRUDA alone in randomized Phase 2 trials in patients with Mismatch Repair/Microsatellite Instable High (dMMR/MSI-H) Metastatic Colorectal Cancer (CRC)....'We look forward to presenting preliminary data in 2023.' Under the terms of the agreement, MSD will supply KEYTRUDA. Nouscom retains all worldwide commercial rights to NOUS-209."

Licensing / partnership • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: National Cancer Institute (NCI) | Phase classification: P2 ➔ P1/2

IO biomarker • Phase classification • Genetic Disorders • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI