Everest Medicines has initiated clinical evaluation of its personalized messenger RNA (mRNA) cancer vaccine, EVM16, with the first patient dosed at Peking University Cancer Hospital in China. The first-in-human (FIH) trial, designated EVM16CX01, marks a significant milestone in the company's oncology pipeline development.
The investigator-initiated trial is being conducted at both Peking University Cancer Hospital and Fudan University Shanghai Cancer Center. It aims to assess the vaccine's safety, tolerability, immunogenicity, and preliminary efficacy as both a standalone treatment and in combination with programmed cell death protein 1 (PD-1) antibody therapy in patients with advanced or recurrent solid tumors.
Trial Design and Objectives
The primary objectives of the EVM16CX01 study include evaluating the safety and tolerability of EVM16 as monotherapy and in combination with PD-1 antibody, as well as determining the recommended Phase II dose (RP2D). Secondary objectives focus on assessing the vaccine's immunogenicity and initial efficacy when used in combination with PD-1 inhibitors.
"EVM16 is a customized vaccine based on each patient's tumor-specific mutations, and using the cutting-edge mRNA technology, to activate the patient's tumor-specific immune response to recognize and attack tumor cells," explained Professor Shen Lin, Director of the Gastrointestinal Oncology Department at Beijing Cancer Hospital and Chair of the Gastric Cancer Expert Committee of the Chinese Society of Clinical Oncology.
Technology Platform and Mechanism
EVM16 is designed to encode multiple tumor neoantigens identified through Everest's proprietary tumor neoantigen AI-based algorithm system, EVER-NEO-1. The vaccine utilizes lipid nanoparticle (LNP) delivery systems to efficiently deliver neoantigen-expressing mRNAs into the human body.
Once administered, these mRNAs produce neoantigen peptides that activate neoantigen-specific T cell immune responses targeted at killing tumor cells. This approach represents a personalized strategy to harness the patient's own immune system against their specific cancer.
Preclinical data has shown promising results, with the combination of EVM16 and PD-1 antibody demonstrating synergistic anti-tumor effects. Toxicity studies indicated that repeated dosing with EVM16 was well-tolerated and safe, supporting its advancement to human trials.
Addressing Unmet Needs in Cancer Treatment
According to Globocan's 2022 data, there were nearly 20 million new cancer cases globally, with 9.74 million cancer-related deaths. While immunotherapies including checkpoint inhibitors have revolutionized treatment for some cancers, they remain effective in only a subset of patients.
"Immunotherapy including checkpoint inhibitors has become an important part of treating some cancer types. However, they are only effective for some patients, and there is an urgent need to develop new generations of immunotherapies, such as personalized mRNA cancer vaccines, that have demonstrated early promise in clinical setting," noted the company in its announcement.
Expanding mRNA Oncology Pipeline
Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines, highlighted the significance of this milestone: "The first patient dosing marks a significant milestone in its clinical development of EVM16, indicating our proprietary tumor neoantigen AI-based algorithm system and mRNA technology platform have advanced to human trials."
Everest Medicines is developing a comprehensive suite of mRNA cancer therapeutics beyond EVM16, including additional personalized cancer vaccines (PCVs), tumor-associated antigen (TAA) vaccines, and immunomodulatory cancer vaccines. The company plans to file investigational new drug applications for its TAA vaccines in both the United States and China in 2025.
Luo emphasized the company's strategic focus on AI-driven drug development: "In recent years, AI has become a major force in drug development, especially in the area of mRNA vaccines. AI is increasingly seen as a crucial tool for boosting research efficiency and accuracy, attracting substantial attention from both the biopharmaceutical industry and governments worldwide."
The company has been optimizing its algorithms since 2021 to enhance the precision of neoantigen recognition and validation, providing what Luo describes as "a strong foundation and a competitive edge in developing mRNA-based cancer vaccines."
Future Outlook
As the trial progresses, Everest Medicines aims to demonstrate EVM16's therapeutic potential and eventually offer innovative treatment options to cancer patients globally. The company's focus on personalized medicine approaches reflects the broader industry trend toward tailored immunotherapies that may overcome the limitations of current treatment options.
Professor Shen Lin expressed optimism about the trial's prospects: "We are confident in achieving positive outcomes in the upcoming clinical trials, bringing hope to cancer patients."
