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) 32nd 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 αCTLA-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, αCTLA-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 αCTLA-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 αCTLA-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 αCTLA-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.
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SOURCE Tocagen Inc.