SAN DIEGO – July 6, 2016 – RiboMed Biotechnologies, Inc. and Tocagen Inc., today announced a collaboration to analyze potential epigenetic prognostic and predictive markers, including the gene for the DNA repair enzyme O-6-Methylguanine-DNA Methyltransferase (MGMT), in Tocagen’s clinical trials evaluating the investigational treatment Toca 511 & Toca FC in patients with recurrent high grade gliomas (HGGs).
HGGs, including glioblastoma, are the most aggressive primary malignant brain tumors and are treated initially with surgery, radiation and chemotherapy, including temozolomide (TMZ, Temodar®). Response to TMZ treatment is variable and almost all tumors ultimately recur. Tumor sensitivity to TMZ correlates with the inactivation of MGMT and longer overall survival in patients with glioblastoma. Inactivation of MGMT is primarily caused by DNA methylation in the MGMT gene’s control region.
Given the prognostic and predictive value of MGMT methylation status, this test has become an informative tool in the management of glioblastoma. RiboMed has developed a new validated test, which improves the reliability and accuracy of MGMT testing. A full description and validation of this technology and comparison to other commonly used DNA methylation methods was recently published in Epigenomics (http://www.futuremedicine.com/doi/pdf/10.2217/epi-2016-0004).
“Accurate diagnostics information is critical to help inform treatment decisions and expectations for outcomes,” said David Piccioni, M.D., Ph.D., neuro-oncologist at UC San Diego’s Moores Cancer Center. “Having a test that can produce accurate and reliable MGMT promoter methylation data with minimal sample is an important advance for patients and their caregivers”.
Favorable safety and promising survival data from Tocagen’s Phase 1, open-label, ascending dose, multicenter trial, that included analysis of epigenetic markers of tumors by RiboMed were published in the cover article of the June 1, 2016 issue of Science Translational Medicine (http://stm.sciencemag.org/content/8/341/341ra75). Based on the positive results reported in this study, Tocagen is now conducting an international Phase 2/3 trial, Toca 5; more information can be found by searching www.clinicaltrials.gov using the clinical trial identifier NCT 02414165). In collaboration with RiboMed, the assay will be utilized to analyze MGMT status in tumors resected during the trial and evaluate association with potential treatment activity.
The collaborative research also includes evaluation of RiboMed’s GliomaSTRAT assay initially in tumor samples from earlier clinical trials. GliomaSTRAT is designed to stratify gliomas by both tumor aggressiveness and potential for drug activity. In addition to MGMT methylation, GliomaSTRAT includes a DNA methylation biomarker panel to determine the tumor’s CpG Island Methylator Phenotype (CIMP) and detection of the IDH1 R132H mutation known to cause CIMP. These prognostic biomarkers identify two distinct tumor subtypes that show significant differences in overall survival, independent of initial tumor grade classification.
The ability to reliably analyze HGGs for multiple DNA methylation biomarkers, particularly with minimal material from FFPE tumor samples, has only recently become possible through the development of RiboMed’s extremely sensitive detection method for measuring both DNA methylation and point mutations using its core technology, Abscription®.
RiboMed Biotechnologies, Inc. is a CLIA-certified molecular diagnostic clinical laboratory and Contract Research Organization offering ultra-sensitive DNA methylation based tests for cancer and drug response related biomarkers to physicians and for use in clinical trials. RiboMed’s test for stratifying glioma brain tumors, GliomaSTRAT™, uses a combination of DNA methylation profiling and mutation analysis to both determine glioma grade (LGG vs HGG) and has been reported to predict response to first line chemotherapy with temozolomide. Research Use Only (RUO) kits, reagents, and technology licensing are also available. For more information go to www.RiboMed.com or follow @RiboMed.
Tocagen is a clinical-stage, cancer-selective gene therapy company focused on developing first-in-class, broadly applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. More information about the clinical trial can be found at www.tocagen.com/toca5. Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in newly diagnosed HGG and metastatic cancer, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit www.tocagen.com or follow @Tocagen.