NEW YORK – Denovo Biopharma said Tuesday that California's Institute for Regenerative Medicine (CIRM) has awarded an $11.8 million grant to Denovo and its partners to develop the investigational biomarker-guided gene therapy DB107 as treatment for certain glioma patients.
Denovo is partnering with the contract research organization Anova Enterprises as well as the California academic institutions UCSF, UCSD, and USC to advance the treatment in a Phase I/IIa clinical trial in up to 70 patients with newly diagnosed high-grade gliomas, including glioblastoma.
Denovo's gene therapy includes two components. The first component, DB107-RRV, involves a recombinant retroviral vector (RRV) bearing cytosine deaminase, which patients receive intratumorally and intravenously. This is combined with the second component, DB107-FC, which is an oral prodrug. The mechanism is meant to selectively infect and kill cancer cells while stimulating the immune system to attack the cancer. The DB107-RRV part of the treatment converts the oral DB107-FC part into the chemotherapy 5-FU but only once it gets to the tumor sites. According to Denovo, this allows the cytotoxic chemo drugs to more powerfully and selectively attack tumor cells with far less systemic exposure to chemo toxicities.
As a primary endpoint in the Phase I/IIa trial, investigators are assessing whether DB107 plus radiation improves patients' progression-free survival versus standard-of-care temozolomide and radiation. In an earlier clinical trial of DB107, the gene therapy did not improve overall survival versus standard of care in an all-comers glioma population. However, retrospective data suggested a benefit among a subgroup of patients enriched for a genetic biomarker dubbed Denovo Genomic Marker 7 (DGM7). For this new clinical trial, patients will be screened for DGM7 status when they enroll in the trial then tracked to determine the biomarker's effect on clinical outcomes.
"We are excited to test the DGM7 biomarker to see if we can identify patients who may benefit the most from this unique gene therapy approach," UCSF researcher and DB107 study investigator Noriyuki Kasahara said in a statement.
For its part of the collaboration, the contract research organization Anova will manage the delivery of DB107 in the trial, which will take place at the three partnered California institutions. Anova, which helped develop the product, also applied for and secured the CIRM award.
"The CIRM grant provides continued validation of Denovo's approach to discovering new genetic biomarkers and developing biomarker-guided therapies," Denovo Chief Medical Officer and Chief Development Officer Matthew Spear said in a statement.