On October 19, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that the first patient has been treated in a Phase 2 clinical trial evaluating the mRNA-based individualized neoantigen-specific immunotherapy (iNeST) candidate autogene cevumeran (also known as BNT122, RO7198457) in resected pancreatic ductal adenocarcinoma (PDAC) (Press release, BioNTech, OCT 19, 2023, View Source [SID1234636138]). PDACs are solid tumors with a poor prognosis reflected in a 5-year overall survival rate of only 8-10%1,2, high recurrence rates3 and limited treatment options.

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Autogene cevumeran, which is being jointly developed by BioNTech and Genentech, a member of the Roche Group, is a therapeutic, individualized cancer vaccine candidate encoding up to 20 patient-specific cancer mutations selected for their proficiency to serve as neoantigens. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells. The investigational treatment aims to induce a neoantigen-directed immune response against the patient’s individual tumor.

The open-label, multicenter, randomized Phase 2 trial (NCT05968326), sponsored by Genentech, will evaluate the efficacy and safety of autogene cevumeran in combination with anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared to the current standard-of-care chemotherapy (mFOLFIRINOX). The Phase 2 study is expected to enroll 260 patients with resected PDAC, who have not received prior systemic anti-cancer treatment and showed no evidence of disease after surgery. The trial will be conducted at various sites in the United States, followed by Europe and Asia Pacific region. The primary endpoint is disease-free survival. Secondary endpoints include disease-free survival rates, overall survival, overall survival rate and safety profile.

The Phase 2 initiation is based on data from an investigator-initiated, single-center Phase 1 trial (NCT04161755) evaluating the combination of autogene cevumeran (BNT122, RO7198457), atezolizumab, and chemotherapy (mFOLFIRINOX) in patients with resected PDAC. Preliminary data of the Phase 1 trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting in June 2022 and complete study results were recently published in Nature, demonstrating a favorable safety profile and substantial vaccine-induced T cell responses that may correlate with delayed PDAC recurrence.

"PDAC is a tumor type for which the relapse rate after surgery is extremely high at nearly 80%. The recent Phase 1 study has shown that individualized neoantigen vaccination is feasible for this tumor type with low mutational burden and an immunosuppressive microenvironment3. We have been evaluating cancer mutations since the start of the first clinical trial based on our mRNA technology in 2014 with the hypothesis that they could be suitable targets for individualized cancer vaccines," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The Phase 2 study will provide additional data whether our approach with autogene cevumeran has the potential to provide a benefit for patients in this high unmet medical need setting. Our aim is to prevent relapses and thus ensure that the disease is managed at the earliest possible stage."

Autogene cevumeran (BNT122, RO7198457) is part of BioNTech’s and Genentech’s worldwide strategic collaboration to develop, manufacture and commercialize novel mRNA-based, individualized cancer vaccines, which was initiated in 2016. Autogene cevumeran is currently being evaluated in various solid tumor indications, including a Phase 2 trial (NCT04486378) in the adjuvant treatment of surgically resected colorectal cancer, a Phase 2 proof-of-concept study (NCT03815058) of autogene cevumeran in combination with pembrolizumab in the first-line treatment of advanced melanoma and a Phase 1a/b trial in locally advanced or metastatic tumors (NCT03289962). The Phase 2 trial of autogene cevumeran in patients with PDAC is the third later-stage trial based on BioNTech’s individualized cancer vaccine platform iNeST.

About resected pancreatic ductal adenocarcinoma (PDAC)
PDAC is amongst the leading causes of cancer-related deaths in the United States4 with approximately 90% of patients dying within two years of their diagnosis5. A combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes, however, even with surgical resection, the relapse rate remains high, and the 5-year overall survival is only approximately 20%6 in patients who undergo surgery followed by adjuvant chemotherapy ("ACT") and only 8-10%1,2 in those who do not receive ACT. Thus, there is a high unmet medical need for novel therapies for patients with resected PDAC. The individualized neoantigen specific immunotherapy ("iNeST") candidate autogene cevumeran (BNT122, RO7198457) provides a novel treatment strategy aimed to induce de-novo immune responses against cancer-specific neoantigens, recognize residual cancer cells and to prevent relapse.

About iNeST (individualized Neoantigen Specific immunoTherapy)
iNeST immunotherapies are individualized cancer therapies tailored to a specific patient’s tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsulated in BioNTech’s proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient’s tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood to help the immune system to recognize the cancer. For this purpose, BioNTech has developed an on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions.

An iNeST Fact Sheet and images from the iNeST manufacturing process are available in the newsroom section on BioNTech’s website at this link.