Enterome SA presented encouraging interim data from its Phase 1/2 AUDREY trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrating that its OncoMimics™ immunotherapy EO4010 combined with nivolumab achieved meaningful survival outcomes in patients with microsatellite stable (MSS)/mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC), a notoriously difficult-to-treat cancer subtype.
The clinical-stage biopharmaceutical company reported that among 20 patients with MSS/pMMR mCRC treated with EO4010 plus nivolumab, survival reached 40% at 12 months with a median follow-up of 15.4 months. The median survival currently stands at 11.3 months, with survival appearing to plateau at 34%, as 7 of 20 patients remain alive.
Novel Immunotherapy Mechanism Shows Promise
EO4010 represents a first-in-class OncoMimics™ immunotherapy that combines five microbial-derived peptides designed to mimic HLA-A2 restricted CD8+ T cell epitopes from five human tumor-associated antigens (TAAs) commonly observed in colorectal cancer patients: BIRC5, FOXM1, UBE2C, CDC20, and KIF2C. The treatment also includes a CD4 helper peptide, Universal Cancer Peptide 2 (UCP2), to enhance immune activation.
"These exciting interim clinical data exemplify the strong therapeutic potential of our OncoMimics™ immunotherapy for cancer," said Pierre Bélichard, Chief Executive Officer of Enterome. "Current treatment options are limited for cancers like MSS/pMMR mCRC, and, so far, EO4010 has already delivered promising survival outcomes and objective responses including in liver metastases without complex side effects."
The OncoMimics™ platform works by activating pre-existing effector memory T cells against bacterial peptides that strongly cross-react with corresponding tumor-associated antigens. This approach circumvents thymic deletion, a process whereby the immune system learns not to attack "self" proteins, by tricking the immune system with peptides different enough from TAAs to raise an immune response against both the OncoMimics™ and the TAAs.
Strong Immune Response and Safety Profile
The AUDREY trial data showed that EO4010 plus nivolumab, with or without bevacizumab, was well tolerated across the patient population. Notably, 80% of patients treated with the combination showed specific immune responses against the tumor-associated antigens targeted by the OncoMimics™ immunotherapy.
"Objective response is a very rare event in immunotherapy in patients with MSS/pMMR mCRC; yet we observed direct tumor impact by EO4010 as measured by CT scan tumor shrinkages and CEA/CA19-9 tumor marker declines, including RECIST partial response in liver and lung metastases," said Jan Fagerberg, MD, PhD, Chief Medical Officer of Enterome.
The treatment generated fast, robust, and durable expansions of CD8+ T cells against the targeted TAAs, resulting in clinically meaningful responses in this challenging patient population. EO4010 continues to demonstrate excellent safety and tolerability throughout the trial.
Addressing Critical Unmet Need
Dr. Arvind Dasari, Professor at the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at MD Anderson Cancer Center and principal investigator presenting the AUDREY data at ASCO, emphasized the clinical significance of these findings. "Treatment options for metastatic colorectal cancer remain limited, and the interim data generated on EO4010 so far indicate that it might add to the treatment possibilities for CRC. EO4010 has shown it can induce targeted immune responses and shrinkage of metastases."
Colorectal cancer represents a significant global health burden as the third most common cancer in men and second in women, contributing to 10% of all cancers worldwide. It ranks as the fourth most common cause of cancer-related death, with more than 600,000 deaths annually. Despite advances in surgery and adjuvant therapy, 25% of patients with localized CRC later develop metastases, and approximately 20% of cases are metastatic at diagnosis. Fewer than 20% of those diagnosed with recurring/metastatic disease survive beyond 5 years from diagnosis.
Trial Design and Future Development
AUDREY (EOCRC2-22/NCT05589597) is a multicenter, open-label Phase 1/2 trial investigating EO4010 as monotherapy and in combination with nivolumab with or without bevacizumab for treatment of patients with unresectable, previously treated, MSS/pMMR mCRC. The trial is assessing safety, tolerability, immunogenicity, and preliminary efficacy in patients enrolled at sites in Europe and the USA.
The positive interim data support further development of EO4010 to treat colorectal cancer, with Enterome positioning the therapy as a potential welcome addition to the therapeutic armamentarium for CRC. The company's pioneering approach to drug discovery is based on its bacterial Mimicry drug discovery platform, which leverages big-data insights from millions of gut bacterial proteins to discover OncoMimics™ with high similarity to tumor-associated antigens.
