On May 19, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported that it will present for the first time proof-of-concept data from clinical trials with EO2401, its first-in-class off-the-shelf OncoMimics cancer immunotherapy at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 3-7, 2022 in Chicago and virtually (Press release, Enterome, MAY 19, 2022, View Source [SID1234614902]).
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OncoMimics peptides – generating strong CD8+ T-cell responses derived from pre-existing memory cells
OncoMimics peptides are gut microbiome-derived peptides that closely mimic antigens expressed by tumor cells. In contrast to tumor antigens, however, OncoMimics peptides are recognized by the immune system as "non-self" and can generate a strong human cytotoxic CD8+ response steming from memory T cells, offering enormous potential to create a new class of cancer vaccines targeting solid and liquid tumors.
Enterome’s pioneering work on its OncoMimics pipeline leverages the fundamental understanding that the gut is the largest lymphoid organ in the body and is home to most of its memory T-cells. As a result, there is constant interaction and presentation of peptides and proteins secreted by gut bacteria to the body’s immune system, resulting in the formation of a pool of effector memory T cells protecting the human body against bacterial invasion. In the event that the bacterial antigens are mimics of tumor antigens, this process leads to the generation of circulating effector memory T cells with a preserved ability to recognize tumor antigens.
To-date, Enterome has generated a repertoire of OncoMimics peptides correlating to tumor antigens across a wide range of solid and liquid tumor types. From this, the Company is creating a pipeline of off-the-shelf cancer immunotherapies designed to act via the same novel mode of action. The first candidates include EO2401 (in clinical trials for glioblastoma and adrenal malignancies), EO2463 (in clinical development for liquid tumors) and EO4010 (in development for colorectal cancer, and targeted to enter clinical trials in 2023).
Enterome’s lead candidate EO2401 combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1, all of which are known driver antigens present on aggressive solid tumors and generate strong human CD8+ responses. In addition, EO2401 contains a CD4 helper peptide UCP4.
At ASCO (Free ASCO Whitepaper), in the first two abstracts, Enterome will present, for the first time, clinical proof-of-concept data from Phase 1/2 clinical trials of EO2401 in combination with an immune checkpoint inhibitor (nivolumab, Opdivo), for the treatment of patients with first progression/recurrence of glioblastoma (the ROSALIE trial, EOGBM1-18) and for the treatment of patients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma (the SPENCER trial, EOADR1-19).
In a third abstract, the Company will present the use of its second therapeutic vaccine program, EO2463 as monotherapy and in combination with lenalidomide and rituximab, for treatment of patients with indolent non-Hodgkin lymphoma (the SIDNEY trial, EONHL1-20). EO2463 combines four OncoMimics peptides that exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), respectively.
Jan Fagerberg, Chief Medical Officer of Enterome said, "As a proof-of-concept for the entire Mimicry platform, we have put in action a clinical development strategy for EO2401 that is designed to identify a clinical efficacy signal in various tumor types that have in common the same tumor antigens (IL13Ra2, BIRC5 and FOXM1). In both the ROSALIE and SPENCER trials, EO2401 in combination with checkpoint blockade generated strong systemic immune responses directed against human tumor antigens. We look forward to sharing these very promising clinical data at ASCO (Free ASCO Whitepaper) while continuing to progress these trials, with the aim of providing a more mature set of data at ESMO (Free ESMO Whitepaper), Europe’s leading medical oncology conference, later in the year."
Enterome’s Mimicry Platform
Enterome’s Mimicry drug discovery platform is based on its unique ability to decode the interaction between the gut microbiome and the immune system. The Mimicry platform uses best-in-class biocomputational tools and bioassays to identify novel therapeutics from its proprietary database of 21 million full-length gut microbiome peptides and proteins.
The Mimicry platform is highly productive and has already generated first-in-class small protein and peptide drug candidates targeting multiple therapeutic areas that modulate the immune system by closely mimicking the structure, effect or actions of specific human antigens, hormones or cytokines.
"We are thrilled to be able to present the first clinical data demonstrating the potential of our unique OncoMimics pipeline at ASCO (Free ASCO Whitepaper) this year. We are using our Mimicry platform to generate multiple pipelines of transformative drug candidates, targeting a broad range of therapeutic areas. Presently we are advancing two pipelines of distinct drug candidates – OncoMimics and EndoMimics – which have the potential to address cancer, inflammatory and autoimmune diseases," said Pierre Belichard, CEO of Enterome. "We believe that our unique platform has the potential to create effective new medicines that make a real difference to patients. Our corporate strategy is designed to advance the development of these new therapies as quickly and robustly as possible while generating significant value for our shareholders. Enterome’s future has never looked so exciting."