Neo Vax (NEO-PV-01) / BioNTech - LARVOL DELTA

SELECTION OF TARGETED NEOANTIGENS FOR ONGOING PERSONALIZED CANCER VACCINE TRIALS AT DANA FARBER CANCER INSTITUTE (IMMUNOLOGY 2025) - P1 | "For the PCV platform (NeoVax), we design up to 24 synthetic long peptides, eighteen to thirty-two amino acids in length...For future iterations, we aim to enhance pipeline by including novel classes of neoantigens, such as those derived from endogenous human retroviruses, fusion epitopes, novel or unannotated open reading frames (nuORFs), and neoantigens identified through immunopeptidome analysis. The neoantigen selection pipeline is currently supporting seven cancer vaccine trials at DFCI.Keywords: Animals Human; Cells T Cells; Molecules Antigens/Peptides/Epitopes MHC; Processes Antigen Presentation/Processing"

Tumor-specific neoantigens • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Personalized Neoantigen Cancer Vaccine + Pembrolizumab After Rituximab for Follicular Lymphoma (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Feb 2024 ➔ Dec 2026

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jan 2027 ➔ Sep 2030 | Trial primary completion date: Jan 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

NeoVax Plus Ipilimumab in Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Patrick Ott, MD, PhD | Trial primary completion date: Dec 2024 ➔ Jan 2026

Trial primary completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | N=20 ➔ 11

Combination therapy • Enrollment change • Metastases • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

NeoVax Plus Ipilimumab in Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Patrick Ott, MD, PhD | Trial completion date: Sep 2026 ➔ May 2030

Trial completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Personalized NeoAntigen Cancer Vaccine w RT Plus Pembrolizumab for Patients With Newly Diagnosed GBM (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

NeoVax With Nivolumab in Patients With Ovarian Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2024 ➔ Apr 2025

Enrollment closed • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma. (PubMed, Clin Cancer Res) - "Collectively, our findings suggest NeoVax did stimulate expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in GBM patients."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IFNG

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dana-Farber Cancer Institute | N=20 ➔ 30

Combination therapy • Enrollment change • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Personalized Neoantigen Cancer Vaccine + Pembrolizumab After Rituximab for Follicular Lymphoma (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Mar 2026 ➔ Dec 2033

Combination therapy • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Melanoma • Oncology • Solid Tumor

Personalized Neoantigen Cancer Vaccine + Pembrolizumab After Rituximab for Follicular Lymphoma (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

NeoVax Plus Ipilimumab in Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Patrick Ott, MD, PhD | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Personalized Neoantigen Cancer Vaccine in Treatment Naïve, Asymptomatic Patients With IGHV Unmutated CLL. (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Mar 2025 ➔ Mar 2028 | Trial primary completion date: Mar 2023 ➔ Mar 2026

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • IGH

NeoVax + CDX-301 and Nivolumab in Melanoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jan 2023 ➔ Jan 2025

Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

[VIRTUAL] A personal neoantigen vaccine NEO-PV-01 in combination with chemotherapy and pembrolizumab induces broad de novo immune responses in first line, non-squamous NSCLC (SITC 2020) - P1b | "Conclusions NEO-PV-01 in combination with pembrolizumab and carboplatin/pemetrexed is feasible, has a good safety profile, and induces de novo immune responses in first line non-squamous NSCLC. The association of baseline disease characteristics to prolonged PFS suggests future patient enrichment strategies for evaluation of this novel regimen in a phase 2 trial."

Clinical • Combination therapy • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • TMB

Comprehensive gene expression analysis of the tumor microenvironment in patients with advanced cancer treated with a personalized neoantigen vaccine, NEO-PV-01, in combination with anti-PD1 (AACR 2019) - P1; "Treatment with nivolumab and NEO-PV-01 leads to changes in the tumor microenvironment that are consistent with cell types and phenotypes that could contribute to an anti-tumor response."

Biomarker • Clinical • Combination therapy • IO Biomarker • PD(L)-1 Biomarker • Tumor microenvironment • Tumor-specific neoantigens

NeoVax Plus Ipilimumab in Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=19 | Recruiting | Sponsor: Patrick Ott, MD, PhD | Trial completion date: Sep 2024 ➔ Sep 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

The personalized vaccine, NEO-PV-01 with anti-PD1, induces neoantigen-specific de novo immune responses in patients with advanced metastatic melanoma: Association with clinical outcomes (AACR 2019) - P1; "Treatment with NEO-PV-01 + adjuvant in combination with nivolumab induced broad de novo neoantigen-specific immune responses in metastatic melanoma. Immune responses were specific and correlations with clinical outcomes will be discussed."

Clinical • Clinical data • IO biomarker • PD(L)-1 Biomarker • Tumor-specific neoantigens • Bladder Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer. (PubMed, Cancer Cell) - "Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). Neoantigen-specific CD4 T cells generated post-vaccination revealed effector and cytotoxic phenotypes with increased CD4 T cell infiltration in the post-vaccine tumor biopsy. Collectively, these data support the safety and immunogenicity of this regimen in advanced non-squamous NSCLC."

IO biomarker • Journal • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • KRAS

Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. (PubMed, Cancer Cell) - "report a phase 1b clinical trial combining a personalized vaccine NEO-PV-01 with chemotherapy and anti-PD-1 pembrolizumab in first-line metastatic non-squamous NSCLC. They demonstrate that this treatment regimen was well tolerated and induced neoantigen-specific CD4 T cell responses with effector phenotype."

Journal • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4

NeoVax With Nivolumab in Patients With Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Apr 2028 ➔ Apr 2029 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

NeoVax + CDX-301 and Nivolumab in Advanced Melanoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Personalized Neoantigen Cancer Vaccine + Pembrolizumab After Rituximab for Follicular Lymphoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • IFNG