Tocagen Announces Updates from FDA Meeting and Clinical Data Presentations at AANS/CNS

Tocagen Presents Updated Interim Survival Data from Ongoing Clinical Studies at American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Section on Tumors

Following Meeting with FDA, Company Advances Towards Pivotal Phase 2/3 Trial in Patients with Recurrent High Grade Glioma

WASHINGTON, D.C. – May 4, 2015 – Tocagen Inc. a clinical-stage immuno-oncology company, today announced updated interim data from Tocagen’s ongoing investigational studies were presented at the 11th Biennial Satellite Symposium of the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Section on Tumors, held May 1-2, 2015, in Washington, D.C. In addition, Tocagen announced the company held a meeting with FDA and continues to advance towards initiation of a pivotal, randomized, controlled Phase 2/3 trial of Toca 511 & Toca FC in patients with recurrent glioblastoma and recurrent anaplastic astrocytoma this year.

“Based on the strength of our interim clinical data involving Toca 511 & Toca FC and a positive meeting with FDA, we continue to move forward with our plans to initiate a pivotal Phase 2/3 trial in 2015,” said Harry Gruber, M.D., chief executive officer of Tocagen. “Initiating this trial is an important advance towards a potential new treatment for patients with primary brain cancer.”

The podium presentations were delivered by Manish K. Aghi, M.D., associate professor of neurological surgery at the University of California, San Francisco, and Michael A. Vogelbaum, M.D., Ph.D., professor of neurosurgery at the Cleveland Clinic, on behalf of the clinical investigators participating in the trials.
“High grade glioma is an extremely deadly disease and there is a great need for new treatments that prolong patient survival,” said Dr. Vogelbaum. “With encouraging safety data and preliminary evidence of clinical activity in two independent studies we look forward to helping advance Toca 511 & Toca FC into a randomized, controlled trial.”

Interim results from an ongoing study, which forms the basis of the planned Phase 2/3 trial design, included 38 patients with recurrent high grade glioma. In this study, Toca 511 was administered into the resection cavity wall at the time of surgery, followed by cycles of orally administered Toca FC. Results are summarized as follows:

  • Median overall survival was 13.7 months across the efficacy evaluable high grade glioma study population, compared to historical benchmarks of around 7 to 8 months.
  • Patients with high grade glioma at first or second recurrence, the subgroup that mirrors the anticipated patient population in the Phase 2/3 trial, had a median overall survival of 14.6 months.
  • Four partial responses identified by independent radiology review support antitumor activity.
  • There was a trend towards increased survival for higher dose cohorts versus lower dose cohorts.
  • Safety was excellent with only one grade 3/4 related event and one subject with Toca FC discontinued for toxicity. The most common related adverse event was fatigue.

In addition, preliminary results from a second ongoing study involving 38 patients with recurrent high grade glioma that had Toca 511 administered transcranially into the tumor, followed by cycles of orally administered Toca FC, were presented. Results are summarized as follows:

  • 17 of 38 patients survived for more than one year, including two patients who were alive beyond three years as of April 4, 2015.
  • Independent radiology review revealed a clinical benefit rate of 46 percent, with 15 of 35 patients showing stable disease at week eight. One patient had a partial response.
  • Delivery of Toca 511 via two different methods showed median overall survival of 13.8 months and 10.6 months compared to historical benchmarks of approximately 7 to 8 months.

Interim results from Tocagen’s ongoing study administering intravenous (IV) Toca 511 in 11 patients with recurrent glioblastoma scheduled for tumor resection and subsequent Toca 511 injections into the resection cavity wall were also presented. Results are summarized as follows:

  • Preliminary data show all subjects remain alive to date, with two patients alive at fourteen and eleven months respectively.
  • Viral DNA encoding cytosine deaminase (CD) and the CD protein were detected in resected tumor samples, indicating that IV delivery results in integration and expression of the vector in the tumor and demonstrating potential for treating other tumor types with systemic infusions. Tocagen is planning to initiate a study of Toca 511 & Toca FC delivered intravenously to patients with metastatic solid tumors.

About Toca 511 & Toca FC

Toca 511 & Toca FC is a combination treatment being investigated in four clinical trials in patients with recurrent high grade glioma, including glioblastoma. A pivotal Phase 2/3 study in patients with recurrent glioblastoma or anaplastic astrocytoma (the “Toca 5” study) is anticipated to initiate in 2015. The combination of Toca 511 & Toca FC is designed to break immune tolerance to the tumor using a combination of mechanisms. Toca 511, a retroviral replicating vector (RRV), delivers a prodrug-activating gene selectively to cancer cells. Then the prodrug-activating enzyme produced in the cancer cell converts orally administered Toca FC, an investigational extended-release formulation of 5-fluorocytosine (5-FC), into a powerful antimetabolite, 5-fluorouracil (5 FU), which kills the infected cancer cell and neighboring 5-FU sensitive tumor cells. Glioma cells and myeloid derived suppressor cells in the tumor are known to be sensitive to 5-FU. In animal models, the production of 5-FU locally kills dividing tumor cells during 5-FC cycles, which leads to durable and selective anticancer immune responses. Data from ongoing clinical trials show encouraging evidence for increased survival compared to historical benchmarks, excellent safety, and evidence to support the proposed mechanism of action.

About Tocagen Inc.

Tocagen is a clinical-stage biopharmaceutical company pursuing the discovery, development and commercialization of gene therapy products using a broadly applicable, cancer-selective immuno-oncology platform. These products leverage retroviral replicating vectors (RRVs) that selectively infect cancer cells creating a factory of RRV in the tumor, which can then infect other cancer cells. These therapies are designed to help patients fight their cancer by locally activating their immune system selectively and broadly against multiple tumor associated antigens through a combination of mechanisms resulting in a durable, systemic benefit. Tocagen’s lead program is entering late-stage clinical development for patients with recurrent high grade glioma (glioblastoma or anaplastic astrocytoma).

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 please visit www.tocagen.com or www.clinicaltrials.gov using the identifier NCT01470794, NCT01156584, NCT01985256, or NCT02414165.