Tocagen Presents Updated Durable Complete Response Data from Phase 1 Trial of Toca 511 & Toca FC in Recurrent High-Grade Glioma

SAN DIEGO, Oct. 27, 2017 /PRNewswire/ -- Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, today reported updated data demonstrating long-term durable responses, and the conversion of initial partial responses (PRs) into complete responses (CRs), from a Phase 1 study of Tocagen's investigational product, Toca 511 & Toca FC, for the treatment of patients with recurrent high-grade glioma (HGG), a type of brain tumor. These updated Phase 1 data were selected for inclusion in the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics official press program (abstract A085) and will be presented in a scientific session at 10:50 a.m. ET today by Clark Chen, M.D., Ph.D., Lyle French Chair in Neurosurgery and head of the University of Minnesota Medical School Department of Neurosurgery.

HGGs are among the most common and aggressive primary brain cancers. Approximately 160,000 patients worldwide are expected to be diagnosed with HGG in 2017. The two most common forms of HGGs are glioblastoma and anaplastic astrocytoma. With current standard of care, recurrent HGG patients have a median survival of approximately seven to nine months.

Tocagen's Phase 1 ascending-dose trial involved 56 patients across seven clinical sites, who, at the time of surgical resection, received Toca 511, followed by multiple courses of Toca FC. Some of the cohorts within the study combined the investigational therapy with antiangiogenic therapy (bevacizumab) or chemotherapy (lomustine). Data highlights are below.¹ The full presentation can be found on Tocagen's website.

Overall Phase 1 Trial Data Summary:

• Toca 511 & Toca FC continued to demonstrate a favorable safety profile and were well tolerated by patients.
• Tocagen has previously presented CR and PR data for the six patients who responded to treatment. The data presented today is updated to show that two previously announced PRs have converted into CRs, bringing the total number of CRs to six.
• Five CRs followed treatment with Toca 511 & Toca FC, and one CR followed combination treatment with Toca 511 & Toca FC and bevacizumab.
• Three of the CRs were glioblastoma IDH1 wildtype, one CR was anaplastic astrocytoma IDH1 wildtype and two CRs were anaplastic astrocytoma IDH1 mutant
• Responses were observed across six different clinical sites.
• All responders are complete responders and remain in response. Median duration of response had not been reached after a median follow-up of 35.1 months (range: 9.2 to 44.9 months).
• An association between durable response and overall survival is suggested as all responders remain alive following study entry (range: 21.4 to 52.2 months).

Toca 5 Qualifying Patient Subgroup:

• In a subgroup analysis of 23 patients in the Phase 1 trial who were in the high-dose cohorts and would qualify for Tocagen's ongoing, Phase 3 Toca 5 trial:
• Five of 23 patients had a durable complete response, bringing the durable response rate (objective responses lasting at least 24 weeks) to 21.7%.²
• Median duration of response had not been reached after a median follow up of 35.7 months (range: 14.1 to 44.9 months).
• Stable disease (lasting at least 8 weeks) was observed in 5 additional patients, bringing the clinical benefit rate to 43.5% (10/23 patients).
• Median survival was 14.4 months.
• Landmark overall survival rates at two and three years (OS24, OS36) was 34.8% and 26.1% respectively.

"Once high-grade glioma recurs, the expected survival is typically measured in months. At recurrence, physicians and caregivers are left with limited treatment options," said Dr. Chen. "Today's results show some high-grade glioma patients are experiencing complete responses and living multiple years after receiving Toca 511 & Toca FC. The duration of response and the number of patients with durable response or stable disease are impressive in this Phase 1 study, supporting further evaluation of Toca 511 & Toca FC as a potential treatment for recurrent high-grade glioma."

Added Asha Das, M.D., senior vice president and chief medical officer of Tocagen, "Patients and physicians urgently await new treatments for high-grade glioma, one of the deadliest cancers. We are encouraged by the maturing durable response results of our earlier trial, and remain committed to advancing Toca 511 & Toca FC through the ongoing Phase 3 Toca 5 trial to bring a potentially transformative product to patients as quickly as possible."

About the Toca 5 Trial

Toca 5 is a Phase 3, pivotal, randomized, double-blind study of Toca 511 & Toca FC in patients with recurrent high-grade glioma, a type of brain tumor. The study is being conducted at 167 sites globally and is expected to enroll 380 patients. Patients will be randomized following surgical resection 1:1 to receive either the Toca 511 & Toca FC regimen or chemotherapy. The primary endpoint of the trial is overall survival (OS). The primary endpoint assumes a median OS of 9.8 months for the control arm versus 14.3 months for the Toca 511 & Toca FC arm. A total of 257 events will provide the study with 85% power to detect a hazard ratio of 0.685. Interim analyses are planned at 50% and 75% of events. More information can be found at www.tocagen.com/toca5 or by searching clinicaltrials.gov using the clinical trial identifier NCT02414165.

About Toca 511 & Toca FC

Tocagen's lead product candidate is a cancer-selective immunotherapy comprised of an investigational biologic, Toca 511, and an investigational small molecule, Toca FC, that are designed to be used together. Toca 511 is an injectable retroviral replicating vector (RRV) that encodes a prodrug activator enzyme, cytosine deaminase (CD). CD is derived from yeast, and humans do not naturally have this gene. Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD. Toca FC is an investigational orally administered prodrug, 5-fluorocytosine (5-FC) that is inactive as an anti-cancer drug. In animal models, Tocagen has shown that 5-FC is converted into the anticancer drug, 5-FU, at high concentrations in Toca 511-infected cancer cells that are producing CD. Together, the Toca 511 & Toca FC combination directly kills cancer cells and immune-suppressive myeloid cells resulting in activation of the immune system against the cancer.

About Tocagen

Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient's immune system against their own cancer. Tocagen is developing its lead investigational product candidate, Toca 511 & Toca FC, initially for the treatment of recurrent highgrade glioma (HGG), a disease with significant unmet medical need. The U.S. Food and Drug Administration (FDA) has granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG and the European Medicines Agency (EMA) has granted Toca 511 PRIME (PRIority MEdicines) designation for the treatment of HGG.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding our business plans and objectives, expectations regarding the timing and success of our clinical trials and planned clinical trials. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost and timing of our product candidate development activities and planned clinical trials; our ability to execute on our strategy; regulatory developments in the United States and foreign countries; and our estimates regarding expenses, future revenue and capital requirements. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Tocagen's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Tocagen undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

¹Data cutoff date was Aug. 15, 2017.

²Responses were assessed using Macdonald Criteria including MRI assessment by independent radiology review and clinical data.

SOURCE Tocagen Inc.

Related Links

http://www.tocagen.com