The clinical data includes details of immunologic trends in patients with recurrent high-grade glioma (rHGG) from a Phase 1 study of Toca 511 (vocimagene amiretrorepvec) and Toca FC (flucytosine, extended-release). Additionally, new preclinical data will be presented demonstrating increased survival from the combination of Toca 511 and flucytosine with either temozolomide or cyclophosphamide. 

Summaries are provided below; full posters or presentations will be placed on Tocagen’s website following the presentation.

Details of the AACR presentation are as follows:

Presentation Type: Poster (Abstract: 4771)
Title: The addition of Toca 511 and 5-FC to temozolomide improves response in a temozolomide-resistant murine glioblastoma model and correlates with Toca 511 dose
Presenter: Maria E. Rodriguez-Aguirre
Date and Time: Wednesday, April 3, 8:00 a.m.-12:00 p.m. ET 
Summary:

• This study aimed to assess the interaction of temozolomide with escalating doses of Toca 511 in an orthotopic temozolomide-resistant murine glioma model.
• Even with lympho-depleting temozolomide treatment, survival was prolonged with moderate levels (30-50 percent) of tumor transduction of Toca 511 with 5-FC but not with lower transduction rates (10 percent).
• Data from this study may inform the evaluation of Toca 511 & Toca FC in combination with temozolomide in patients with newly diagnosed glioblastoma (GBM).

Details of the AANS presentations are as follows:

Presentation Type: E-Poster displayed online (Abstract: 2120)
Title: Immune Monitoring of High-Grade Glioma Patients in a Phase 1 Clinical Trial of Toca 511 and Toca FC
Presenter: Steven Kalkanis, M.D.
Summary:

• Human immune monitoring results from a Phase 1 clinical trial of Toca 511 & Toca FC support an immune-related mechanism of action for the regimen.
• Univariate comparisons and multivariate models revealed pre-treatment tumor infiltrating cell subsets quantified via deconvolution of RNA sequencing data were associated with both objective responses and survival.
• Post-treatment serum cytokine time-course results suggest that differences in temporal modulations are associated with both objective response and survival.
• These results indicate the value of evaluating potential biomarkers of patient outcomes in the ongoing randomized Toca 5 Phase 3 trial in patients with recurrent HGG.

Presentation Type: Oral (Abstract: 481)
Title: Toca 511 and 5-FC in Combination with Metronomic Cyclophosphamide Reduces Treg Cells and Enhances Therapy Efficacy in a Preclinical Murine Model
Presenter: David Piccioni, M.D., Ph.D.
Date and Time: Wednesday, April 17, 4:49-4:52 p.m. PT 
Summary:

• This study aimed to determine if the addition of metronomic cyclophosphamide would provide therapeutic benefit when combined with Toca 511 and 5-FC (5-fluorocytosine) in a preclinical, subcutaneous glioma model.
• The addition of metronomic cyclophosphamide improved tumor control and survival, and led to a superior CD8+/Treg ratio in the peripheral blood.
• Results support the further evaluation of Toca 511 & Toca FC with metronomic dosing of cyclophosphamide and potentially other chemotherapeutics.

About Toca 511 & Toca FC
Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). 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, 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 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’s lead investigational product candidate, Toca 511 & Toca FC, is under evaluation in a pivotal Phase 3 trial (Toca 5) for recurrent high grade glioma (HGG), a disease with significant unmet medical need. The U.S. Food and Drug Administration awarded Tocagen an orphan drug grant for the Toca 5 trial and has granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG. The European Medicines Agency has granted Toca 511 PRIME (PRIority MEdicines) designation for the treatment of glioma.

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 results of our and our collaborator’s clinical trials and planned clinical trials, expectations regarding the timing of regulatory submissions and reviews, expectations regarding our preclinical research and development activities, expectations regarding our use of cash in 2019, and plans related to development of our current and future product candidates in additional indications.  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.

Media Contact:
Pam Lord
Canale Communications
(619) 849-6003
[email protected]  

Investor Contact:
Pete Rahmer
Endurance Advisors
(415) 515-9763
[email protected]