Inhibigen (MMP9FS) / Genocea - LARVOL DELTA

Long term results from a phase 1 trial of GEN-009, a personalized neoantigen vaccine, combined with PD-1 inhibition in advanced solid tumors (SITC 2021) - P1/2 | "Background GEN-009 adjuvanted personalized cancer vaccine contains up to 20 neoantigens selected by ATLAS™, an ex vivo bioassay screening autologous T-cells for immune responses against both neoantigens and Inhibigens™. Preliminary data demonstrate induction of robust, durable neoantigen-specific immune responses and epitope spreading in the presence of PD-1 CPI. Broad immunity against tumor specific targets and encouraging patient outcomes support further study.Trial Registration clinicaltrials.gov identifier: NCT03633110"

P1 data • Tumor-specific neoantigens • Oncology • Solid Tumor • CD4 • CD8

The PLANET manufacturing process reproducibly generates high-quality neoantigen-targeted peripheral T cells (NPTs) for adoptive T cell therapy in the TiTAN clinical trial (AACR 2022) - P1 | "Patient-specific neoAgs against which their T cells were responsive were identified with ATLAS, and up to 30 neoAgs were prioritized for manufacture; pro-tumor Inhibigens™ were excluded. NPTs can routinely be manufactured in a GMP setting to treat patients with solid tumors. By expanding fresh, non-exhausted NeoAg-specific T cells with known tumor specificity from the periphery, GEN-011 has the potential to provide clinical benefits of TIL with greater accessibility and minimal irrelevant T cells. The TiTAN trial is ongoing."

Clinical • IO biomarker • Tumor-specific neoantigens • Head and Neck Cancer • Lung Cancer • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

ATLAS-identified Inhibigen-specific responses accelerate tumor growth in mouse melanoma and pancreatic cancer (AACR 2022) - P1 | "Genocea’s GEN-011 neoantigen-targeted peripheral T cell (NPT) therapy candidate, designed using ATLAS-identified neoantigens and omitting Inhibigens, is being evaluated in an ongoing clinical trial (NCT04596033). Continued exploration of mechanisms of action of Inhibigen-specific responses may reveal new paradigms of cancer immune evasion. 1H Lam et al, Cancer Discov 2021;11:1-18"

Preclinical • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8

TiTAN: a phase 1 study of GEN-011, a neoantigen-targeted peripheral blood-derived T cell therapy with broad neoantigen targeting. (AACR 2022) - "Maximum grade 2 CRS and one grade 2 ICANS peaked around day 8 in parallel to cell expansion and no patients required tocilizumab or corticosteroids. Taken together, these early data support the biological activity of GEN-011. Using a personalized immune assay to identify neoantigens, and to exclude Inhibigens, to generate tumor specific T cells may offer a more accessible and promising ACT for treating solid tumors."

P1 data • Tumor-specific neoantigens • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

GEN-009, a personalized neoantigen vaccine candidate, elicits diverse and durable immune responses associated with clinical efficacy outcomes (SITC 2021) - P1/2 | "Background GEN-009, a personalized vaccine candidate comprised of ATLAS™-prioritized neoantigens combined with Hiltonol®, is currently being evaluated in a Phase 1/2a clinical trial (NCT03633110). ATLAS™ is a cell-based recall assay that, without predictions, screens each patient‘s mutanome to identify neoantigens for vaccine inclusion and deleterious Inhibigens™ for exclusion...These data support that GEN-009, in combination with checkpoint blockade, represents a unique approach to treat solid tumors. ETHICS STATEMENT This study was approved by Western Institutional Review Board, approval number 1-1078861-1"

Clinical • IO biomarker • Tumor-specific neoantigens • Oncology • Solid Tumor • CD4 • CD8

GEN-011-101 (the TiTAN-1 trial): Phase 1 study to evaluate the safety, proliferation and persistence of GEN-011, an autologous neoantigen-targeted peripheral T cell therapy in solid tumors (SITC 2021) - P1 | "ATLAS will also identify Inhibigens™, antigen targets of T cells that promote tumor growth.1 Autologous peripheral T cells will be specifically stimulated by up to 30 ATLAS-identified neoantigens, avoiding Inhibigens, to generate an adoptive T cell product. Patients will be followed for safety, immunogenicity, and anti-tumor activity over approximately a 5-month treatment period. A long-term follow-up will continue through 2 years after the initial dose of GEN-011.Trial Registration clinicaltrials.gov identifier: NCT04596033"

Clinical • P1 data • Tumor-specific neoantigens • Anal Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Urothelial Cancer • CD4 • CD8 • IL2

Empiric profiling of peripheral T cell recall responses to tumor mutanomes versus in silico predictions in NSCLC patients undergoing pembrolizumab treatment ± chemotherapy (SITC 2021) - "Background Effective immune checkpoint blockade (ICB) treatment is dependent on T-cell recognition of patient-specific mutations (neoantigens). Conclusions Monotherapy and combination therapy had differential effects on CD4:CD8 T cell ratios and their non-specific expansion. A greater proportion of neoantigens was identified than previously reported in studies employing in silico predictions prior to empirical verification.2 Overlap between confirmed antigens and in silico prediction was observed, but in silico prediction continued to have a large false negative rate and could not characterize Inhibigens."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

InhibigenTM administration promotes aberrant T cell responses in cancer but may be beneficial for amelioration of autoimmune disease (SITC 2021) - "Mechanistic studies show altered T cell signaling pathways in the context of therapeutic Inhibigen vaccination. These data suggest that Inhibigen-specific responses, while detrimental for the treatment of cancer, may have a therapeutic benefit in other disease contexts."

IO biomarker • Melanoma • Oncology • Solid Tumor