Interim Data Show Increased Median Overall Survival of Recurrent Brain Cancer Patients Treated with Tocagen's Toca 511 & Toca FC, Compared to Published Benchmarks

MIAMI, Nov. 18, 2014 /PRNewswire/ -- Tocagen Inc. today announced that interim data showed increased median overall survival and progression free survival at six months for recurrent high grade glioma (HGG) patients treated with Toca 511 & Toca FC, compared to published benchmarks. HGG includes glioblastoma, the most common and aggressive form of primary brain cancer. The data were delivered in an oral presentation at the 19^th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO) by Tim Cloughesy, M.D., director of the University of California, Los Angeles (UCLA) Neuro-Oncology Program on behalf of the trial investigators participating in the study. Additional clinical and preclinical studies were also presented at the conference. To date, 78 patients have been dosed with Toca 511 & Toca FC across Tocagen's three ongoing investigational studies.

In the study presented by Dr. Cloughesy, 34 patients with recurrent HGG had Toca 511 administered into the resection cavity wall at the time of surgery followed by cycles of orally administered Toca FC. Median overall survival was 52.0 weeks. Patients with recurrent glioblastoma that had two or fewer prior recurrences had a median overall survival of 59.0 weeks. The presented data with the most relevant historical benchmarks are summarized in the table below:

E. Antonio Chiocca, M.D., Ph.D., professor of neurosurgery, Harvard Medical School, Brigham and Women's Hospital and surgical director at the Center for Neuro-oncology, Dana-Farber Cancer Institute said, "There is an urgent need for effective treatment options for patients with recurrent glioblastoma, and I look forward to seeing this promising gene therapy advance into a randomized controlled trial to determine its effectiveness."

Added Harry Gruber, M.D., chief executive officer of Tocagen, "Based on the safety profile, evidence to support the mechanism of action and survival data from these three ongoing studies, we are now planning to advance Toca 511 & Toca FC into late-stage trials."

In addition, six month progression free survival for patients with glioblastoma was 26.9 percent compared to 6.8 percent for historical published data. Independent radiology review in evaluable patients using bidimensional measurement excluding FLAIR showed four partial responses and seven cases of stable disease for a clinical benefit rate of 36.7 percent (11/30). The partial responses were seen in the higher dose cohorts. Analysis of RNA expression levels in the resected tumors revealed increased survival with Toca 511 & Toca FC treatment with reduced gene expression of a known viral resistance gene in patient tumors. There was one Grade 3 adverse event of transient asthenia that was classified as related to Toca 511.

The following additional interim results from other clinical trials of Toca 511 were also presented in a poster session:

• Interim results showed no drug-related Grade 3 or Grade 4 adverse events for the initial five patients enrolled in a study evaluating ascending doses of intravenous administration of Toca 511 in patients with recurrent glioblastoma scheduled for tumor resection. The treatment has been safe and well tolerated to date. In addition, two of the three patients in the highest dose cohort had quantifiable Toca 511 genes found in resected tumor samples and in the blood. The investigators in this study were represented by lead author Steven Kalkanis, M.D., chair of the department of neurosurgery and co-director of the Neuroscience Institute, Henry Ford Hospital.
• Interim results showed a median overall survival of 53 weeks and survival rate of 93.8 percent at 6 months in a study evaluating direct intratumoral delivery of Toca 511 in patients with recurrent HGG. Historical published data report median overall survival of 33.2 weeks and a six month survival rate of 59 percent. In this study of 37 patients, a favorable safety profile was also demonstrated. The investigators in this study were represented by lead author Manish Aghi, M.D., associate professor of neurological surgery, University of California, San Francisco.

In addition, three preclinical studies related to Toca 511 were presented, as follows: 

• Radiation therapy combined with Toca 511 and multiple cycles of 5-FC treatment significantly prolonged survival in pre-established intracranial U87/EGFRvIII radio-resistant glioma models with a median survival of longer than 89 days (median not reached) for the treated group versus 15 days for the control group, supporting the clinical investigation of Toca 511 and 5-FC in combination with radiation in the first-line or recurrent setting for patients with HGG. The results were presented orally by Masamichi Takahashi, M.D., Ph.D., from the department of neurosurgery and neuro-oncology, National Cancer Center in Tokyo, and the David Geffen School of Medicine at UCLA.
• Toca 511 and 5-FC treatment significantly prolonged survival in an intracranial 231-BR model of CNS-metastatic breast cancer with a median survival of 97.5 days for the treated group versus 45 days for control group, supporting continued investigation in future clinical studies in patients with brain metastases from breast cancer. The poster was presented by Akihito Inagaki, Ph.D., from the department of cell biology, University of Miami, and the David Geffen School of Medicine at UCLA.
• A retroviral replicating vector carrying a gene encoding a codon optimized bacterial nitroreductase A (RRV-NAO), which converts the prodrug CB1954 into an anticancer drug, was evaluated in an intracerebral U87-fLuc2 orthotopic tumor model. Results demonstrated significantly prolonged survival, with 100 percent of mice treated with RRV-NAO followed by multiple prodrug cycles surviving at 80 days, compared to a median survival of 36 days for the prodrug-only control. The poster was presented by Sara Collins, Ph.D., from the department of cell biology, University of Miami, and the David Geffen School of Medicine at UCLA.

About Toca 511 & Toca FC
Toca 511 & Toca FC, the company's lead investigational combination product, is being evaluated in three clinical trials in patients with recurrent high grade glioma, including glioblastoma. Toca 511 & Toca FC, an extended-release formulation of 5-fluorocytosine (5-FC), is designed to have a dual mechanism of action. Toca 511 delivers a prodrug-activating gene selectively to cancer cells. Then the prodrug-activating enzyme produced in the cancer cell activates orally administered Toca FC given in cycles, into a powerful antimetabolite, 5-FU, selectively in the cancer. In animal models, the production of 5-FU locally kills dividing tumor cells during each 5-FC cycle, which leads to durable and selective anticancer immune responses. Data from ongoing clinical trials show encouraging evidence for increased survival compared to historical controls, safety and tolerability, antitumor activity and evidence to support the proposed mechanism of action. Based on these data the company is now planning to commence late-stage clinical trials in patients with high grade glioma.

About Tocagen Inc.
Tocagen is a clinical-stage selective cancer immunotherapy company pursuing discovery, development and commercialization of gene therapy drugs using a novel retroviral replicating vector platform, which selectively infects cancer cells. These therapies are designed to help patients fight their cancer by locally activating their immune system selectively against their cancer, with subsequent systemic benefit. 

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 about Tocagen or Toca 511 & Toca FC please visit www.tocagen.com or www.clinicaltrials.gov using the identifier NCT01470794, NCT01156584 or NCT01985256.

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