On May 14, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported preclinical data on Toca 521, a retroviral replicating vector (RRV) expressing a single-chain variable fragment targeting PD-L1, will be presented at the 2018 Annual Meeting of The American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), held May 16-19 in Chicago (Press release, Tocagen, MAY 14, 2018, View Source;p=RssLanding&cat=news&id=2348847 [SID1234526566]).
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In a preclinical study, Toca 521 reversed PD-1/PD-L1 mediated immune suppression, resulting in robust, durable and highly selective anti-tumor activity that was superior to systemically administered anti-PD-1 or anti-PD-L1 monoclonal antibodies. Tocagen expects to advance Toca 521 into investigational new drug application (IND) enabling studies this year.
In addition, previously disclosed clinical data and new preclinical results from an ovarian cancer model will be presented.
Summaries are provided below for new data sets, for which full posters will be placed on Tocagen’s website following the presentation.
Presentation Type: Poster (Abstract: 111)
Title: PD-L1 Checkpoint Blockade Using a Single-Chain Variable Fragment Targeting PD-L1 Delivered by Retroviral Replicating Vector Enhances Anti-Tumor Effect in Cancer Models
Presenter: Amy Lin, Ph.D., associate director of experimental virology at Tocagen
Date and Time: Wednesday, May 16, 5:30 p.m. CT
Summary:
A RRV expressing a single-chain variable fragment targeting PD-L1, called Toca 521, 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.
These results indicate further development of Toca 521 is warranted 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.
Presentation Type: Oral presentation (Abstract: 344)
Title: Treatment of Recurrent HGG Patients with the Retroviral Replicating Vector Toca 511 and Toca FC Resulted in Durable Responses and Survival Lasting 3 Years or Longer: Immune Mechanisms and Molecular Analyses of Tumors
Presenter: Douglas Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen
Date and Time: Thursday, May 17, 9:20-9:40 a.m. CT
Presentation Type: Poster (Abstract: 428)
Title: Toca 511-Mediated Prodrug Activator Gene Therapy: A Promising Therapeutic Strategy for Ovarian Cancer
Presenter: Sara Collins, Ph.D., assistant scientist in the department of cell biology at the University of Miami Miller School of Medicine. These studies were performed in the laboratory of Noriyuki Kasahara, M.D., Ph.D., professor of cell biology and pathology at the University of Miami.
Date and Time: Thursday, May 17, 5:15 p.m. CT
Summary:
Preclinical studies evaluating Toca 511 and 5-FC in a mouse model of ovarian cancer were conducted.
Increased survival and reduced tumor burden was observed in mice with pre-existing tumors receiving Toca 511 followed by 5-FC, as compared to untreated controls.
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 (vocimagene amiretrorepvec) 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, extended-release formulation of the 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 in the tumor microenvironment resulting in anti-cancer immune activation and subsequent tumor killing.