Enterome Announces First Patient Dosed in Phase 1/2 Trial With Third OncoMimics Immunotherapy in Metastatic Colorectal Cancer

Enterome recently announced the first patient was dosed in the Phase 1/2 AUDREY trial evaluating EO4010, the company’s third OncoMimics candidate, for the treatment of patients with unresectable, previously treated, metastatic colorectal cancer (CRC).

EO4010 is an innovative, off-the-shelf immunotherapy that combines five synthetic OncoMimics peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the tumor-associated antigens (TAAs) BIRC5/survivin, FOXM1, UBE2C, CDC20 and KIF2C. EO4010 also includes universal cancer peptide 2 (UCP2), a helper peptide representing the CD4+ epitope.

The five selected TAAs are associated with critical cell-cycle functions and are highly expressed in CRC tumors but not significantly in healthy tissues. The selection of OncoMimics peptides corresponding to these TAAs ensures broad tumor coverage designed to overcome tumor heterogeneity and reduce tumor escape.

The AUDREY study (EOCRC2-22/NCT05589597) is a multicenter, open-label Phase 1/2 trial assessing safety, tolerability, immunogenicity and preliminary efficacy of EO4010 in monotherapy and in combination with the immune checkpoint inhibitor nivolumab for treatment of metastatic colorectal cancer. A total of 42 patients are expected to be enrolled in Europe and the US.

AUDREY represents the fourth trial investigating Enterome OncoMimics immunotherapy candidates in solid and liquid malignancies. The company is also initiating a Phase 2 clinical study in patients with ctDNA-defined, Minimal Residual Disease of colorectal cancer, with its fourth candidate EO2040.

Dr. Romain Cohen, medical oncologist (MCU-PH) Department of medical oncology, Saint-Antoine hospital, AP-HP, and Assistant Professor of Oncology at Sorbonne University (Paris, France), is Coordinating Investigator for the AUDREY study in France. Dr. Cohen main clinical and research interests include the study of cancers harboring microsatellite instability, particularly their treatment with immune-oncology. He is principal investigator of several clinical trials dedicated to colorectal cancers.

Dr. Cohen commented “After they have received the main standard of care treatments, patients with metastatic colorectal cancer have limited options for more efficacious treatment and as a result have poor clinical outcomes. We look forward to assessing the potential benefits of the novel immunotherapy approach of EO4010 in this frequent and underserved indication and providing updates on the progress of the AUDREY study.”

Pierre Bélichard, Chief Executive Officer of Enterome, added “This new trial evaluating EO4010 in patients with advanced disease of colorectal cancer is another significant milestone for Enterome. Building on the promising data from our ongoing trials investigating EO2401 in recurrent glioblastoma and adrenal tumors, and EO2463 in non-Hodgkin lymphoma, we believe that our upcoming studies with EO4010 and EO2040 in colorectal cancer will reinforce Enterome’s position as a leader in next-generation cancer immunotherapies. Through our OncoMimics immunotherapies, we are able to break the immune tolerance to self-antigens with a technology that is off-the-shelf and enables multi-targeting of tumor antigens. This groundbreaking approach so far demonstrates both efficacy and safety for the patients, instilling real hope in the fight against cancer.”

OncoMimics immunotherapies are designed to activate pre-existing effector memory T cells that target bacterial (non-self) peptides, which are strongly cross-reactive against selected Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid, targeted cytotoxic response against cancer.

EO4010 is Enterome’s third clinical-stage off-the-shelf OncoMimics peptide-based immunotherapy. It combines five microbial-derived OncoMimics peptides that closely mimic cytotoxic T cell (CD8+ T cell), HLA-A2 restricted epitopes, from five different tumor associated antigens (TAAs): BIRC5/survivin, FOXM1, UBE2C (also called UBCH10), CDC20 and KIF2C; (also called MCAK), as well as a helper CD4 peptide, Universal Cancer Peptide 2 (UCP2).

The EO4010 OncoMimics peptides are non-self, high affinity and stable MHC class I binders designed to trigger the immune system into recognizing these epitopes as non-self and eliciting a targeted memory T cell-driven response. The two OncoMimic peptides mimicking BIRC5 and FOXM1, as well as UCP2, have already been validated via Enterome’s EO2401 candidate in more than 150 patients with glioblastoma and adrenal tumors, showing, in combination with nivolumab +/- bevacizumab, the ability to generate strong systemic immune responses against the targeted TAAs correlating with clinical outcome (progression-free survival and objective response), and being well tolerated. Furthermore, in preclinical assays, all healthy donors showed an antigen specific CD8 T cell response against the three new peptides mimicking UBE2C, CDC20 and KIF2C. Expertise gained with previous candidates has allowed Enterome to optimize the composition of EO4010 in only two years.

AUDREY (EOCRC2-22/NCT05589597) is a multicenter, open-label Phase 1/2 trial investigating EO4010 in monotherapy and in combination with nivolumab for treatment of patients with unresectable, previously treated, metastatic colorectal cancer. The trial is assessing safety, tolerability, immunogenicity and preliminary efficacy in 42 patients at centers in Europe and the US. Patient enrollment is ongoing.

Colorectal cancer (CRC) is the third most common tumor in men and the second in women, accounting for 10% of all tumor types worldwide. With more than 600,000 deaths estimated each year, CRC is the fourth most common cancer-related cause of death globally. Despite all efforts regarding surgery and adjuvant therapy, approximately 25% of patients with localized disease will later develop metastases. In addition, 20% of newly diagnosed patients have metastatic disease already at presentation. Thus, CRC continues to be a major therapeutic challenge with a considerable number of patients experiencing premature death, fewer than 20% of those diagnosed with recurring/metastatic disease surviving beyond 5 years from diagnosis.

Enterome is a clinical-stage biopharmaceutical company developing breakthrough immunomodulatory drugs for the treatment of cancer and immune diseases. Enterome’s pioneering approach to drug discovery is based on its unique and powerful bacterial Mimicry drug discovery platform, allowing it to analyze and uncover new biological insights from the millions of gut bacterial proteins in constant cross-talk with the human body. Its first-in-class, small protein and peptide drug candidates modulate the immune system by closely mimicking the structure, effect or actions of specific antigens, hormones, or cytokines. The company’s two pipelines of drug candidates include:

OncoMimics peptides, a pipeline of peptide-based immunotherapies. Lead candidate, EO2401, is in Phase 2 clinical trials in patients with glioblastoma and adrenal tumors and has demonstrated clinical proof of concept. EO2463 is in a Phase 1/2 clinical trial for indolent non-Hodgkin lymphomas, and has demonstrated a good safety profile with first signs of efficacy. EO4010 is in clinical development for third-line colorectal cancer and EO2040 is expected to start a Phase 2 trial in 2023 in patients suffering from colorectal cancer with ctDNA-defined, minimal residual disease.

EndoMimics peptides, a pipeline of next generation bioactive molecules acting like human hormones or cytokines, are being developed in collaboration with Nestlé Health Science, for food allergies and inflammatory bowel disease (IBD). Lead candidate, EB1010, expected to enter clinical development in 2024, is a potent local inducer of IL-10, designed to improve therapeutic outcomes for patients with IBD.

Enterome employs 70 people and is headquartered in Paris, France. Since its inception, the Company has raised a total of €116 million from Europe- and US-based life science investors and more than €100 million from pharmaceutical partnerships. For more information, visit  www.enterome.com.