Intra-Cellular Therapies Presents Data on Antitumor Effects of Phosphodiesterase I Inhibition in a Preclinical Colorectal Can...
April 12 2021 - 7:30AM
Intra-Cellular Therapies, Inc. (Nasdaq: ITCI) today announced a
poster presentation on its PDE1 inhibitor program at the ongoing
2021 American Association for Cancer Research (AACR) Virtual Annual
Meeting, which is being held from April 10 - 15, 2021. Details of
the poster presentation are as follows:
Title: Effects of ITI-214, a Potent and
Selective Phosphodiesterase Type 1 Inhibitor, on Tumor Myeloid
Cellular Composition, Tumor Volume and Survival in Mouse Models of
Colorectal Cancer When Combined with an Anti-PD-1 Checkpoint
Inhibitor (Poster 1243).Session Category:
Experimental and Molecular TherapeuticsSession
Title: Novel Antitumor Agents
The poster describes results from preclinical studies
demonstrating that the Company’s selective PDE1 inhibitor,
lenrispodun (ITI-214), alters the tumor microenvironment and
exhibits compelling anti-tumor activity when combined with a
programmed cell death-1 (PD-1) immune checkpoint inhibitor in an
animal model of colorectal cancer.
In previous studies we have shown the ability of our PDE1
inhibitors to reduce neuroinflammation. In these studies we
discovered a novel intracellular pathway by which the PDE1 enzyme
controls the functions of certain immune cells called microglia
(brain resident macrophage-like cells). We have shown that
inhibition of the activity of these cells by PDE1 inhibitors
reduces inflammation in the brain (O’Brien et al., 2018).
Based on our understanding of the role of PDE1 in regulating the
function of microglia and macrophages, we hypothesized that PDE1
inhibitors would block the recruitment of immunosuppressive cells
(macrophages, monocytes) into the tumor microenvironment (TME) of
certain cancers. By inhibiting PDE1, host immune responses may be
potentiated leading to inhibition of tumor growth.
At AACR we are reporting on pre-clinical studies demonstrating
that lenrispodun alone decreased the numbers of infiltrating
macrophages and increased the numbers of natural killer cells in
the TME. These effects serve to prevent tumors from evading the
host immune system and thereby potentiate the tumor killing
activity of checkpoint inhibitors. When lenrispodun and an
anti-PD-1 antibody were combined, tumor volumes were significantly
reduced and tumor-free survival was significantly increased in a
mouse model of colon carcinoma. Importantly, the effect of
combining an anti-PD-1 immune checkpoint inhibitor and lenrispodun
treatment produced a complete response in about 50% (7/15) of
treated mice as compared to 10% (1/10) in anti-PD-1 alone treated
mice, 20% (1/5) in the lenrispodun alone group and 0% (0/9) in the
control group. This translated into a statistically significant
effect on survival for the combination treatment group as compared
to control (p=0.001).
Tumor associated macrophages can promote tumor growth in certain
cancers. Our experiments indicate PDE1 inhibition prevents the
migration and accumulation of monocytes and macrophages in the
tumor microenvironment and could represent a novel and broadly
applicable approach to the treatment of immune responsive cancers.
We are currently evaluating our PDE1 inhibitors in other cancer
models and are developing potential biomarkers that may assist in
the translation of these data to the treatment of human
cancers.
Phosphodiesterase type 1 (PDE1) inhibitor
Portfolio
Our PDE1 inhibitor program is focused on diseases in which the
PDE1 enzyme is over-expressed and/or abnormal immune cell function
contributes to disease pathology providing opportunities to pursue
innovative treatments for multiple diseases including Parkinson’s
disease, heart failure and other diseases.
Lenrispodun is a potent and selective PDE1 Inhibitor and is the
lead compound in the Company’s PDE1 portfolio. Lenrispodun is in
development for the treatment of symptoms associated with
Parkinson's disease and for the treatment of heart failure.
Lenrispodun has been generally well tolerated with a favorable
safety profile in six Phase 1 clinical trials. Lenrispodun works by
blocking the breakdown of cyclic nucleotides (cAMP, cGMP), thus
allowing these molecules to build up in the cells and to exert
important functions.
Previous studies have described the mechanism of action of
lenrispodun in the brain. The mechanism of action of ITI-214 and
our other PDE1 inhibitors suggests therapeutic potential across a
variety of diseases including neurological and, cardiovascular
diseases and cancer.
About Intra-Cellular Therapies
Intra-Cellular Therapies is a biopharmaceutical company
founded on Nobel prize-winning research that allows us to
understand how therapies affect the inner-workings of cells in the
body. The company leverages this intracellular approach to develop
innovative treatments for people living with complex psychiatric
and neurologic diseases.
Forward-Looking Statements
This news release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of 1995
that involve risks and uncertainties that could cause actual
results to be materially different from historical results or from
any future results expressed or implied by such forward-looking
statements. Such forward-looking statements include statements
regarding, among other things, the therapeutic value, clinical and
non-clinical development plans and commercial potential of our drug
product candidates; the progress, timing and results of our
clinical trials and preclinical studies; our beliefs about the
extent to which the results of our clinical trials and preclinical
studies to date support new drug application filings for product
candidates; the safety and efficacy of our product development
candidates; our beliefs about the potential uses and benefits of
our drug product candidates; and development efforts and plans
under the caption "About Intra-Cellular Therapies." All such
forward-looking statements are based on management's present
expectations and are subject to certain factors, risks and
uncertainties that may cause actual results, outcome of events,
timing and performance to differ materially from those expressed or
implied by such statements. These risks and uncertainties include
but are not limited to the following: our current and planned
clinical trials or other studies for our product candidates may not
be successful or may take longer and be more costly than
anticipated; product candidates that appeared promising in earlier
research and clinical trials may not demonstrate safety and/or
efficacy in larger-scale or later clinical trials; our proposals
with respect to the regulatory path for our product candidates may
not be acceptable to the FDA; our reliance on collaborative
partners and other third parties for development of our product
candidates; the COVID-19 pandemic may negatively impact the conduct
of, and the timing of enrollment, completion and reporting with
respect to, our clinical trials; any other impacts on our business
as a result of or related to the COVID-19 pandemic; and the other
risk factors detailed in our public filings with
the Securities and Exchange Commission. All statements
contained in this press release are made only as of the date of
this press release, and we do not intend to update this information
unless required by law.
Contact:
Intra-Cellular Therapies, Inc.Juan Sanchez, M.D. Vice President,
Corporate Communications and Investor Relations646-440-9333
Burns McClellan, Inc.Lisa
Burnsjgrimaldi@burnsmc.com212-213-0006
Intra Cellular Therapies (NASDAQ:ITCI)
Historical Stock Chart
From Mar 2024 to Apr 2024
Intra Cellular Therapies (NASDAQ:ITCI)
Historical Stock Chart
From Apr 2023 to Apr 2024