On November 6, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported three presentations of updated clinical and preclinical data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting & Pre-Conference Programs, to be held Nov. 7-11 in Washington, D.C., the 3rd CNS Anticancer Drug Discovery and Development Conference (CADDDC), to be held Nov. 14-15 in New Orleans and the 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO), to be held Nov. 15-18 in New Orleans (Press release, Tocagen, NOV 6, 2018, View Source;p=RssLanding&cat=news&id=2375540 [SID1234530869]).

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The clinical data includes details of immunologic trends seen in responding patients with recurrent high grade glioma (HGG) from a Phase 1 study of Toca 511 (vocimagene amiretrorepvec) & Toca FC (5-fluorocytosine, extended-release). Additionally, new preclinical data will be presented demonstrating the enhanced efficacy of Toca 511 & Toca FC regimen when combined with metronomic cyclophosphamide.

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

Details of the SITC (Free SITC Whitepaper) presentation are as follows:

Presentation Type: Poster (Abstract: P620)
Title: Enhanced Efficacy and Combinability of Low Dose Toca 511 and 5-FC with Metronomic Chemotherapy in Preclinical Models
Presenter: Sophie Viaud, Ph.D.
Date and Time: Saturday, Nov. 10, 7:00-8:30 p.m. ET
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.
Regulatory T cells were significantly reduced in the peripheral blood with the combination with metronomic cyclophosphamide and CD8+ T cells were significantly increased.
Results support the further evaluation of Toca 511 & Toca FC with metronomic dosing of cyclophosphamide and potentially other chemotherapeutics.
Details of the CADDDC presentation are as follows:

Presentation Type: Oral Presentation (Abstract: 0023)
Title: PD-L1 Checkpoint Blockade Using a Single-Chain Variable Fragment Targeting PD-L1 Delivered by Retroviral Replicating Vector (Toca 521) Enhances Anti-Tumor Effect in Cancer Models
Presenter: Amy Lin, Ph.D.
Date and Time: Wednesday, Nov. 14, 1:35-1:45 p.m. CST
Summary:

Toca 521, a retroviral replicating vector (RRV) expressing a single-chain variable fragment (scFv) targeting PD-L1, was developed using Tocagen’s proprietary cancer-selective gene therapy platform technology.
Preclinical results demonstrated Toca 521 reversed PD-1/PD-L1 mediated immune suppression in a human in vitro cell culture system, and conferred robust, durable and highly selective anti-tumor activity compared to systemically administered anti-PD-1 or anti-PD-L1 monoclonal antibodies.
Plasma levels of scFv PD-L1 were equivalent to negative control levels and hence very low compared to reported levels in humans given systemic anti-PD1/PD-L1 therapy.
These results warrant further development of Toca 521 to investigate the potential for improved safety and efficacy profiles compared to systemic monoclonal antibodies against the same checkpoint target. Toca 521 could also be useful in combination with other agents, including immuno-oncology therapies.
Details of the SNO presentation are as follows:

Presentation Type: Poster (Abstract: ATIM-26)
Title: Immunologic trends associated with recurrent high grade glioma patient outcomes in a Phase 1 clinical trial of Toca 511 and Toca FC
Presenter: William Accomando, Ph.D.
Date and Time: Saturday, Nov. 17, 5:00-7:00 p.m. CST
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.
Preliminary analyses identified immunologic biomarkers that can potentially predict, with high sensitivity and selectivity, patient outcomes following treatment with Toca 511 & Toca FC.
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.
About Toca 511 & Toca FC
Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising 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 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.