Nouscom’s lead molecule enters Phase 2 clinical trials

NOUS-209 is an off-the-shelf immunotherapy targeting 209 specific neoantigens for the treatment of Mismatch Repair/Microsatellite Instable High (dMMR/MSI-H) unresectable or metastatic gastric, colorectal and gastro-esophageal junction tumors. It is being investigated in multi-center EU and US Phase 2 randomized clinical trials in patients with dMMR/MSI-H unresectable and metastatic colorectal cancer (CRC) (NCT04041310) in combination with checkpoint inhibitors (CPI) versus CPI alone and in patients who have stopped responding to previous anti-PD1 and other approved CPI therapies.

Nouscom is assessing the efficacy and safety of NOUS-209 in combination with pembrolizumab at multiple sites across Europe and the US (NCT04041310). The Phase 2 study will include two cohorts in dMMR/MSI-H unresectable and metastatic colorectal cancer (CRC):

• A randomized cohort enrolling patients who are eligible for first line treatment of NOUS-209 plus pembrolizumab versus pembrolizumab alone;
• A single arm cohort enrolling patients who have stopped responding to previous anti-PD1 and other approved therapies

Marina Udier, Chief Executive Officer of Nouscom, added: "The initiation of the Phase 2 study is another significant milestone this year for our company. Building on our published safety, immunogenicity and mechanism of action clinical data, the trial, together with the Phase 1 'cancer interception' monotherapy study in Lynch Syndrome carriers, will allow us to demonstrate the efficacy of NOUS-209 and illustrate the power of our platform. We look forward to presenting interim results at key conferences during 2023."

Michael J. Overman, Principal Investigator of the trial and Professor in the Department of GastroIntestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, said: "The continued clinical development of NOUS-209 is critical as there remains a significant unmet need in the treatment of CRC, including overcoming tumor resistance to anti-PD1 immunotherapies. Data from the Phase 1 study presented at ASCO 20221 and published in Science Translational Medicine2 demonstrated how NOUS-209 induces neoantigen specific CD8+ T cells which infiltrate metastatic tumors and exert anti-tumor efficacy, providing hope for better treatment options for this patient population with difficult to treat cancers."

Encouraging Phase 1b data for NOUS-PEV

Nouscom’s second candidate in clinical trials is NOUS-PEV. NOUS-PEV is a personalized cancer immunotherapy designed for each patient based on selection and prioritization of mutations unique to that patient’s tumor. Nouscom recently announced data from the Phase 1b clinical trial.

NOUS-PEV is being evaluated in a multicenter Phase 1b open-label, dose confirmation and cohort expansion study (NCT04990479). The Phase 1b trial is assessing the safety, feasibility and preliminary efficacy as per RECIST 1.1 criteria in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with either locally advanced 1L melanoma or 1L non-small cell lung cancer (NSCLC) expressing more than 50% PD-L1.

The key findings are as follows:

• Manufacturing Feasibility: >90% of vaccines successfully manufactured, released and delivered to patients on time
• Safety: Well tolerated with a favorable safety profile - Immunogenicity: Potent neoantigen specific immune responses were detected in all evaluable subjects with clinical responses
• Biomarkers/Immune correlates of clinical efficacy: Deepening of clinical responses coincided with the increase of NOUS-PEV-induced T cells in blood; Increased T cell infiltration in the tumors; NOUS-PEV-induced neoantigen specific T cells identified in tumor biopsies in subjects with clinical responses
• Clinical Efficacy: Clinical responses correlated with biomarker analyses/predictions