Tocagen to Present Updated Clinical and Preclinical Data at Three Scientific Conferences

SAN DIEGO, Nov. 9, 2017 /PRNewswire/ -- Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, today announced seven presentations of updated clinical and preclinical data at the Society for Immunotherapy of Cancer (SITC) 32^nd Annual Meeting & Pre-Conference Programs, held Nov. 8-12 in National Harbor, Maryland, the 2017 Society for Neuro-Oncology (SNO) and the Society for CNS Interstitial Delivery of Therapeutics (SCIDOT) Joint Conference on Therapeutic Delivery to the CNS, held Nov. 15-16 in San Francisco, and the 22nd Annual Scientific Meeting and Education Day of the SNO, held Nov. 16-19 in San Francisco.

The clinical data includes quantitation of the expression of cytosine deaminase (CD) protein in brain tumor samples following intravenous administration of Toca 511, as well as details of immune system activation seen in responding patients from a Phase 1 study. Previously disclosed clinical data will also be reviewed. New preclinical data will also be presented demonstrating the enhanced efficacy of a checkpoint inhibitor when combined with Toca 511 & Toca FC.

Summaries are provided below for new data sets; full posters or presentations will be placed on Tocagen's website following the presentation.

Details of the SITC presentation are as follows:

Presentation Type: Poster (Abstract: P284)
Title: T cell priming by Toca 511 and 5-FC coupled with T regulatory cell depletion by ?CTLA-4 synergistically enhances anti-tumor immune memory in a mouse model of glioma
Presenter: Leah Mitchell, Ph.D., associate director, translational research at Tocagen
Date and Time: Saturday, Nov. 11, 12:30-2:00 p.m. ET and 6:30-8:00 p.m. ET
Summary:

• This study aimed to determine if the addition of a checkpoint inhibitor, ?CTLA-4, would provide therapeutic benefit when combined with Toca 511 and 5-FC in a mouse model of glioma.
• Adoptive transfer of immune cells from animals that cleared their primary tumor through Toca 511, 5-FC, and ?CTLA-4 showed 100% survival benefit to animals bearing orthotopic gliomas, significantly greater than the approximate 50% survival seen with transfer from animals that cleared primary tumor through Toca 511 and 5-FC alone, although at a lower Toca 511 dose.
• Regulatory T cells were significantly reduced with ?CTLA-4 treatment and long-term memory was significantly improved with the combination as shown in adoptive transfer studies.
• These results support the further evaluation of Toca 511 & Toca FC with ?CTLA-4.

Details of the SNO-SCIDOT presentations are as follows:

Presentation Type: Oral
Title: Durable response rate in high grade glioma: An emerging endpoint for immunotherapeutics
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program
Date and Time: Wednesday, Nov. 15, 11:25 a.m. PT

Presentation Type: Poster (Abstract: SCDT-06)
Title: Intravenous delivery of Toca 511 in patients with high grade glioma results in quantifiable expression of cytosine deaminase in tumor tissue
Presenter: Tiffany Montellano, Ph.D., medical science liaison at Tocagen
Date and Time: Wednesday, Nov. 15, 5:00-7:00 p.m. PT
Summary:

• In a Phase 1 study, Toca 511 was administered intravenously to patients with recurrent high-grade glioma. At the time of subsequent tumor resection, tissue from various regions of the tumor was collected and processed for quantitative PCR analysis of CD RNA and DNA.
• CD protein expression quantitation measured by immunohistochemistry and its expression frequency in tumors will be presented.
• Updated clinical response data and additional immunohistochemical assessment to determine spatial correlates between CD protein and T cells including T regulatory cells will also be presented.
• These data show that intravenous delivery of Toca 511 results in appreciable deposition of the virus in the tumor and uptake does not appear to be affected by the extent or nature of the pre-existing T cell infiltrate. 

Details of the SNO presentations are as follows:

Presentation Type: Oral (Abstract: ATIM-21)
Title: Intravenous delivery of Toca 511 in patients with high grade glioma results in quantifiable expression of cytosine deaminase in tumor tissue
Presenter: Tobias Walbert, M.D., Ph.D., co-director of the Hermelin Brain Tumor Center at Henry Ford Hospital
Date and Time: Friday, Nov. 17, 2:10 p.m. PT

Presentation Type: Oral (Abstract: ATIM-02)
Title: Durable responses observed in IDH1 wildtype and mutant recurrent rHGG with Toca 511 & Toca FC treatment
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program
Date and Time: Friday, Nov. 17, 3:40 p.m. PT

Presentation Type: Poster (Abstract: TMIC-42)
Title: Toca 511 and 5-FC induces T cell-mediated antitumor immunity in a mouse glioma model which is enhanced by the addition of a therapeutic antibody against CTLA-4 and correlated with a reduction in memory T regulatory cells
Presenter: Douglas Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen
Date and Time: Saturday, Nov. 17, 5:00 p.m.-7:00 p.m. PT

Presentation Type: E-talk (Abstract: ATIM-25)
Title: Immunological activation in responding patients with recurrent HGG after treatment with Toca 511 & Toca FC: Results from a phase 1 trial
Presenter: Derek Ostertag, Ph.D., director, R&D diagnostics at Tocagen
Date and Time: Saturday, Nov. 18, 5:40 p.m. PT
Summary:

• In a Phase 1 study, patients received Toca 511 via injection into resection cavity walls at the time of surgery followed by oral Toca FC. These data report immunological activation seen in responding patients following treatment.
• Sustained markers of proliferation and immune activation were observed in circulating T cells from patients with response or stable disease and not in those who progressed.
• Responding patients did not have a higher tumor mutational burden compared to non-responding patients.
• Increased tumor infiltrating T cells, as measured by productive TCR sequences, were observed in responding patients at time of surgery.
• Analyses of patient blood samples following treatment showed differences in inflammatory cytokines associated with response to therapy.

About Toca 511 & Toca FC

Tocagen's lead product candidate is a two-part cancer-selective immunotherapy comprised of an investigational biologic, Toca 511, and an investigational small molecule, Toca FC. Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, only infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into high concentrations of an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

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) granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG and the European Medicines Agency (EMA) 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, timing and success of our clinical trials and planned clinical trials, timing of results from our clinical trials and our plans regarding selection of additional product candidates. 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.