Patient Enrollment in the United States Ongoing

SAN DIEGO – March 8, 2016 — Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced that its randomized, controlled Phase 2/3 clinical trial, called Toca 5, has expanded internationally and is now enrolling patients in Canada. The company previously announced in December 2015 that the first patient had been enrolled in the Toca 5 trial in the United States. The study compares the combination of Toca 511 (vocimagene amiretrorepvec) and Toca FC (extended-release 5-fluorocytosine) to standard of care in patients with first or second recurrence of glioblastoma or anaplastic astrocytoma who are undergoing resection.

“Brain tumors are extremely challenging to treat, and with 27 Canadians diagnosed each day there is an urgent need for new therapies,” said Kevin Petrecca, M.D., Ph.D., associate professor and William Feindel Chair in NeuroOncology at the Brain Tumour Research Centre at McGill University’s Montreal Neurological Institute and Hospital, which enrolled the first patient in Canada. “Tocagen’s innovative approach to fighting recurrent brain cancer using cancer-selective gene therapy is the kind of cutting-edge investigational treatment that we want to offer patients at our site – the largest specialized neuroscience research and clinical center in Canada. Our team is thrilled to be the first site to open the Toca 5 study in Canada.”

Added Gelareh Zadeh, M.D., Ph.D., associate professor at the Department of Surgery University of Toronto, Wilkins Family Chair in Brain Tumor Research, and principal investigator for the Toca 5 clinical trial in Canada, “I wish to congratulate Dr. Petrecca and his team for being the first to open this new trial at their institute and I am very encouraged by the promising results for Toca 511 & Toca FC in patients with recurrent glioblastoma and anaplastic astrocytoma we have seen to date. We are working to open additional clinical trial sites across Canada as soon as we can to enable access to this trial for as many Canadians as possible.”

The primary endpoint for the Toca 5 clinical trial is overall survival. Investigators may choose chemotherapy (lomustine or temozolomide) or antiangiogenic therapy (bevacizumab) for the control arm. More information about the clinical trial can be found at www.tocagen.com/toca5.

“With enrollment ongoing in the United States, expanding the study to include patients in Canada is an important milestone for the Canadian brain tumor community as well as for Tocagen,” said Jamey Skillings, M.D., chief medical officer of Tocagen. “We are grateful to the various individuals and groups who contributed to this achievement, and we look forward to opening additional sites internationally as we continue to advance this potential new treatment option for patients with high grade glioma.”

The Canadian Brain Tumour Consortium (CBTC), a national not-for-profit investigator network, is facilitating the Toca 5 trial in Canada under the direction of James Perry, M.D., head of division of neurology at Sunnybrook Health Sciences Centre, University of Toronto and chair of the CBTC.

High grade gliomas (HGGs) are among the most common and aggressive primary brain cancers. In 2016 approximately 160,000 patients worldwide are expected to be diagnosed with HGG. The two most common forms of HGGs are glioblastoma (GBM) and anaplastic astrocytoma. Patients with newly diagnosed GBM who receive maximal therapy have a median survival of approximately 14 to 16 months. Median survival after recurrence is approximately seven to nine months.

As of March 1, 2016, Tocagen has enrolled and treated 128 patients in Phase 1 studies. In these studies, potential benefits were found, including extended overall survival and a favorable safety profile. In particular, patients with recurrent HGG who received Toca 511 at the time of surgical resection of tumor, using the delivery method in the Toca 5 trial, had a median survival of 13.6 months (N=43) and a 12- and 24-month survival rate of 52.5 percent and 31.6 percent, respectively. Patients with first or second recurrence of HGG and no prior bevacizumab, the patient population to be studied in the Toca 5 trial, had a median survival of 14.6 months (N=30). A summary of clinical data from Tocagen’s ongoing Phase 1 clinical trials can be found on Tocagen’s website.

Tocagen’s cancer-selective gene therapy platform is built on retroviral replicating vectors (RRVs) which are designed to selectively integrate into the DNA of cancer cells which then serve as factories for these RRVs to replicate and infect neighboring cancer cells, providing long-term presence of the therapeutic gene(s). Tocagen’s lead product candidate is a combination of an investigational biologic, Toca 511, and an investigational small molecule drug, Toca FC, designed to be used together. Toca 511 is a proprietary injectable RRV that encodes a prodrug activator enzyme, cytosine deaminase (CD). Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD protein. Toca FC is an orally administered, proprietary extended-release version of 5-fluorocytosine, a prodrug that is inactive as an anti-cancer drug. Toca FC is converted into the active anti-cancer drug, 5-fluorouracil, at high concentrations in Toca-511-infected cancer cells that are producing CD protein. 5-FU is a well-established anti-cancer agent used effectively in many conventional chemotherapy settings. In addition to the direct killing of Toca 511-infected cancer cells, treatment is designed for 5-FU to kill neighboring uninfected cancer cells and myeloid derived suppressor cells (MDSCs) in the tumor microenvironment, activating the immune system against the patient’s cancer antigens.

About Tocagen
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 & Toca FC, 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. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the 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.