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Date: 05-Oct-2021

BioNTech Begins Patient Dosing In Phase 2 Trial Of MRNA-based Individualized Immunotherapy BNT122 In Colorectal Cancer Patients

BioNTech SE announced that the first colorectal cancer patient has been treated with its individualized mRNA cancer vaccine BNT122 (autogene cevumeran, RO7198457) in a phase 2 clinical trial. The trial has been initiated in the United States, Germany, Spain and Belgium. It is planned to enroll about 200 patients to evaluate the efficacy of RO7198457 (BNT122) compared to watchful waiting after surgery and chemotherapy, the current standard of care for these high-risk patients. As the second deadliest cancer worldwide, the medical need for novel therapies to treat colorectal cancer remains high.

The open-label phase 2 trial (NCT04486378) is investigating autogene cevumeran in stage II/III colorectal cancer patients after surgical resection of their tumor and completion of adjuvant chemotherapy. The current standard of care in this indication is watchful waiting to see if tumors recur after removal of the primary tumor and adjuvant chemotherapy. A proportion of these patients are expected to have a recurrence of their tumor within 2-3 years after their surgery: in the clinical trial, patients at high risk for recurrence will be identified early on with a highly sensitive blood test detecting circulating tumor DNA (ctDNA). The phase 2 trial will investigate the efficacy of autogene cevumeran as a single agent compared to standard of care watchful waiting in this high-risk patient population. The primary endpoint for the study is disease-free survival (DFS). Secondary objectives include relapse-free survival (RFS), overall survival (OS) and safety. The first patient in the trial has been treated at a clinical site in Europe.

“This trial is an important milestone in our efforts to bringing individualized immunotherapies to patients.” said Özlem Türeci, M.D., co-founder and chief medical officer of BioNTech. “Many cancers progress in such a way that the patient initially appears tumor-free after surgery, but after some time tumor foci that were initially invisible grow and form metastases. In this clinical trial in patients with colorectal cancer, we aim to identify high-risk patients with a blood test and investigate whether an individualized mRNA vaccine can prevent such relapses.”

The phase 2 trial is based on previous results from the phase 1a/1b basket trial evaluating autogene cevumeran as a single agent and in combination with atezolizumab, an anti-PD-L1 antibody, in patients with solid tumors (NCT03289962). The data show the induction of neoantigen-specific T cell responses, a manageable safety profile and objective responses as indication of clinical activity. In parallel to the ongoing phase 2 study, BioNTech has initiated an epidemiological study (NCT04813627) to investigate ctDNA status in patients with stage II/III colorectal cancer following resection or prior to adjuvant chemotherapy to identify patients who might be potential candidates for the Pphase 2 trial. In Germany, trial screening is supported by the molecular registry Colopredict Plus 2.0 (AIO-KRK-0413/ass) of the Association for Internal Oncology (AIO), a working group of the German Cancer Society, and the Ruhr University Bochum.

Autogene cevumeran is an individualized neoantigen specific immunotherapy (iNeST) and the lead candidate from BioNTech’s mRNA-based cancer vaccine platform. Since 2016, BioNTech has advanced mRNA-based cancer vaccines targeting neoantigens in collaboration with its partner Genentech, a member of the Roche Group, including the joint clinical development of autogene cevumeran in a phase 1a/1b basket trial in solid tumors and a randomized phase 2 study in first-line melanoma patients, which was initiated in 2019. BioNTech will sponsor and operationalize the colorectal cancer phase 2 trial. Joint development with Genentech of autogene cevumeran in other trials with Genentech will continue. The companies are equally sharing development costs and potential profits from their joint development of mRNA-based cancer vaccines targeting neoantigens for the potential treatment of multiple cancers.

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. 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 encapsuled 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 a first of its kind, on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions.

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