We believe that to truly advance precision medicine, it is critical to understand the dominant biology, or the underlying biological drivers of a cancer. Unlike DNA mutations that reflect historical events in the cancer’s evolution that may no longer be driving the cancer, messenger RNA (mRNA) expression reflects the biological processes that are in action at the time of biopsy. We believe that using RNA expression signatures to describe tumor biology offers scientists and clinicians a more real-time synopsis of the patient’s cancer than DNA mutational analysis.
OncXerna Therapeutics has developed its Xernaᵀᴹ platform using proprietary RNA-based gene expression data and machine learning-based algorithms to classify patients based on the dominant biologies of their cancer. The first panel from this platform focuses on the tumor microenviroment (TME Panel) and is based on the interplay between angiogenic and immunogenic dominant biologies of the TME, and has been developed as a clinical assay. OncXerna’s pipeline of clinical-stage programs with known mechanisms of action directly address the subtypes identified by the Xernaᵀᴹ TME Panel. OncXerna plans to identify new areas of cancer biology to identify new subtypes and expand its pipeline with clinical-stage programs that match these subtypes. With this approach, OncXerna aims to dramatically improve the success rate of clinical trials by enriching the intent-to-treat patient population with those patients whose dominant biology is the best fit for the mechanism of action of our compounds. This offers the potential to radically alter the clinical development process, improve patient outcomes, speed the delivery of novel drugs to patients, and demonstrate new ways to deliver on the promise of precision medicine.
The Xernaᵀᴹ TME Panel is an investigational assay that has not been licensed or approved and has not been demonstrated to be safe or effective for any use.
Dominant biology focus
Categorizing the dominant biology of a patient’s tumor opens up multiple new opportunities to expand precision medicine to relatively large groups of patients, and potentially, in a tumor agnostic way. For example, we estimate that subgroups of patients in our leading biomarker panel represent 15-40% of the addressable patients in the solid tumor indications studied thus far.
In the future, this approach may be amenable for patients who may benefit from novel targeted therapies that currently are not enabled by the current state of precision medicine. Many well-studied mechanisms of cancer biology are not linked to DNA mutational profiles, therefore, posing a challenge for the field to identify indications for such novel mechanisms as well as which patients to treat.
Xernaᵀᴹ TME Panel and bioinformatics-driven patient algorithms
OncXerna’s Xernaᵀᴹ TME panel is specific to the tumor microenvironment. It separates patients based on their unique biological features such as immune responses limited by checkpoint molecules, by immune-suppressive cells and cytokines, or by aggressive cancer angiogenesis, all of which can impact a patient’s response to treatment.
The Xernaᵀᴹ Platform categorizes patients into one of the following four subtypes that are distinct regardless of cancer stage: angiogenic (A), immune suppressed (IS), immune active (IA) and immune desert (ID).
See our founder’s RNA-based Biomarker panel publication which served as inspiration for OncXerna’s efforts to build clinical assays from RNA signatures.
Xernaᵀᴹ Platform Posters/Presentations
Xernaᵀᴹ Platform Posters/Presentations
ASCO 2023 – Abstract 228: Biomarker Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab
SITC 2022 – Xerna tumor microenvironment subtypes as a biomarker in lung cancer patients
ESMO 2022 – Predicting benefit from maintenance durvalumab after first-line chemotherapy (1L CTx) in oesophagogastric adenocarcinoma (OGA) using a novel tumour microenvironment (TME) RNA assay
Working Towards Precision Medicine for the Tumor Microenvironment
Development of an RNA-based Diagnostic Platform Based on the Tumor Microenvironment Dominant Biology
RNA-Based Diagnostic Panel Matches TME Phenotype to Therapeutic Mechanism of Action in Colorectal Cancer
Xerna™TME Panel: A pan-cancer RNA-based investigational assay designed to predict patient response to angiogenic- and immune-targeted therapies
OncXerna Therapeutics Announces Journal of Clinical Oncology Publication Featuring Phase 1b Data of Navicixizumab Plus Paclitaxel in Ovarian Cancer
Matching the right patient with the right treatment
A cancerous tumor and its surrounding environment are complex, and there is no one-size-fits-all treatment solution for the majority of patients without targetable genetic drivers of their disease. Our knowledge of a patient’s dominant biology has enabled us to generate proposed treatment algorithms to advance our pipeline of clinical-stage programs. Our two lead compounds target molecules with known mechanisms of action relevant to the tumor microenvironment. By enriching our trials with the patients most likely to benefit from these mechanisms of action and excluding those patients who are not likely to benefit, we hope to improve clinical development with speed, increased accuracy, and enhanced clinical benefit to those treated.
OncXerna plans to focus its next generation of panels on cancer biologies outside the tumor microenvironment and by doing so, could enable the growth of our pipeline and expand the dominant biology vision. Our ultimate goal is to develop tissue agnostic biomarkers, based on RNA, that have the potential to work across any tumor-type, enabling the use of meaningful precision therapies to treat the majority of people with cancer.
Learn more about how the Xernaᵀᴹ Platform supports OncXerna’s clinical pipeline.