Genocea Biosciences, Inc. presents updated immunogenicity and clinical response data from the GEN-009 Phase 1 trial that continue to validate the company’s unique and differentiated approach to identifying clinically meaningful immunotherapy targets through the proprietary ATLAS selection process. Long-term results demonstrate that GEN-009 continues to generate broad immune responses against neoantigens that can lead to sustained clinical responses. In Part A of the study, designed to measure safety and immunogenicity only, eight patients with no measurable disease were vaccinated with GEN-009 as a monotherapy. Six of the eight patients continue without recurrence with a median follow up of 25 months post start of the vaccination. Notably, as previously reported, GEN-009 elicited T cell immune responses to 99% of the ATLAS-selected neoantigens, the seen across neoantigen vaccine programs. In Part B, patients were enrolled at the initiation of a PD-1 checkpoint inhibitor (CPI)-based standard of care (SOC) regimen for advanced or metastatic disease; patients who were controlled on SOC and did not require alternate therapy are labeled CPI-sensitive, patients who required alternate therapy before vaccination are labeled CPI-refractory. Of the nine CPI-sensitive patients, the latest data show four patients experienced novel reduction in tumor volume post-GEN-009 dosing and achieved independent RECIST responses after vaccination, including three partial responses (PRs) and one complete response (CR). This is an increase from the two PRs and one CR previously reported at SITC 2020. The remaining five CPI-sensitive patients all achieved disease stabilization. Across the CPI-sensitive cohort, the median duration without disease progression after initial GEN-009 vaccination was 15 months. Of the seven CPI-refractory patients, two achieved stable disease after initial GEN-009 vaccination for up to 10 months. GEN-009 has been well tolerated with only mild adverse events associated with the vaccine adjuvant. Expanded immunogenicity data from Part B of the study revealed that vaccine-specific T cell responses were detected ex vivo after the first dose of the vaccine and continued to rise with each subsequent dose. Vaccine-specific T cell responses remained significantly elevated over baseline and post-CPI, pre-vaccine timepoints for at least 6 months, showing persistence of the vaccine response. CPI-sensitive subjects had a greater number of neoantigens identified with ATLAS at baseline compared with patients in the CPI-refractory cohort, and also had evidence of epitope spread for CD8+ T cells post-dosing. Additionally, the magnitude of CD4+ T cell responses were greater for the CPI-refractory than CPI-sensitive subjects, despite a reduced proportion of peptides to which CD4+ T cell responses were measured, suggesting that the breadth and not the magnitude of response could be associated with favorable outcomes.