Tocagen to Accelerate Toca 511 & Toca FC Development into Pivotal Phase 3 Trial

SAN DIEGO, Oct. 26, 2017 /PRNewswire/ -- Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, today announced the company has updated the protocol of the ongoing Toca 5 clinical trial of Toca 511 & Toca FC for the treatment of patients with recurrent high-grade glioma (HGG), a type of brain tumor.

Based on Tocagen's communications with the U.S. Food and Drug Administration (FDA) under Breakthrough Therapy Designation, Tocagen will immediately accelerate Toca 511 & Toca FC clinical development by modifying the original two-step trial design (Phase 2 followed by a Phase 3) into a seamless, pivotal trial, known as the Toca 5 trial.

"We are pleased with the outcome of our discussions with FDA under Breakthrough Therapy Designation, resulting in a pivotal Phase 3 trial," said Marty Duvall, chief executive officer of Tocagen. "This advance allows us to expedite development of Toca 511 & Toca FC in support of our mission to bring clinicians and patients a new treatment option for this aggressive form of brain cancer." 

Highlights of the revised trial design are as follows:

• An additional 193 patients with recurrent HGG will be enrolled and pooled with 187 already enrolled patients, for a total target enrollment of 380 patients.
• 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.
• Secondary endpoints of the trial include durable response rate, defined as complete or partial responses lasting at least 24 weeks, which is being assessed as a novel endpoint in the post-surgical setting of recurrent HGG.
• The updated protocol includes planned interim analyses at 50% and 75% of events, estimated to occur in the second half of 2018 and first half of 2019, respectively. Due to this transition to a seamless trial design, a previously planned data analysis of the Phase 2 portion of the original Phase 2/3 trial will no longer occur.
• Additionally, the FDA awarded Tocagen a $2 million orphan drug grant, payable over four years, to support the Toca 5 trial. More details on the grant are available at FDA.gov.

"The maturing data from our Phase 1 resection trial in patients with recurrent brain cancer gives us confidence to move forward with a seamless pivotal trial rather than waiting to initiate a separate Phase 3 study," said Asha Das, M.D., senior vice president and chief medical officer of Tocagen. "We will be sharing these updated data in an oral presentation at the AACR-NCI-EORTC meeting tomorrow."

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 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 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 high grade 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 of our clinical trials, including the timing of enrollment, interim analyses and results from our 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.

SOURCE Tocagen Inc.

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