-- Small-Molecule Inhibitors Enhance Immune System and May Offer
Advantages over Existing Cancer Therapies --
SEATTLE--(BUSINESS WIRE)--Dec. 5, 2016--
Omeros Corporation (NASDAQ: OMER) today announced that its
small-molecule inhibitors against GPR174, an orphan G protein-coupled
receptor (GPCR) narrowly expressed in immune cells and linked to
cancers, substantially and statistically significantly boost levels of
cytokines and reduce the population of a subset of T cells known as
regulatory T cells (Tregs), both activities known to be important in
cancer immunotherapy. Based on these findings, the compounds being
advanced by Omeros hold potential advantages over both chimeric antigen
receptor (CAR) T-cell therapy and checkpoint inhibitors, each highly
touted immunotherapies in development for the treatment of multiple
cancers. Part of its orphan GPCR program, Omeros believes that the
company alone has identified compounds that inhibit GPR174, and Omeros
is establishing a broad patent position directed to any GPR174 inhibitor
for the treatment of cancer.
In assays with human peripheral blood mononuclear cells (PBMCs)
evaluating T-cell proliferation and survival following T-cell
stimulation, Omeros discovered that small-molecule GPR174 inhibitors
increase, with statistical significance, the levels of cytokines
interleukin 2 (IL-2) and interferon gamma (IFN-γ) multiple-fold and
nearly doubled interleukin 10 (IL-10). Moreover, GPR174 inhibition
statistically significantly reduced by approximately 40 percent the
population of Tregs, a subset of T-cells elevated in a large number of
cancers. Data from GPR174 inhibition in mouse PBMCs are consistent with
the human PBMC findings. Importantly, the compound effects were not
observed in PBMCs derived from mice genetically lacking GPR174,
indicating that the robust Omeros compound effects are the result of
“on-target” interaction with the orphan receptor.
These results demonstrate that GPR174 inhibition potentiates the
activity of effector T cells, which produce cytokines and are known to
be integral to combatting cancer. Also, reducing the level of Tregs is a
key objective in cancer immunotherapy, and high levels of Tregs in solid
tumors frequently correlates with poor patient outcomes. In addition,
signaling and mechanistic studies support that GPR174 suppresses
anti-tumor activity, and inhibitors of GPR174 are expected to counteract
that detrimental suppression.
“The data from Omeros’ GPR174 program are exciting, as they may lead to
a new approach to increase immune function through simultaneous
modulation of multiple immune cell subsets,” stated Marc Gavin, Ph.D.,
Research Associate Member, Benaroya Research Institute. “GPR174
inhibition represents a wholly new mechanism in cancer immunotherapy,
one that may offer the combined effects of cytokine stimulation and Treg
reduction across a wide variety of cancers. This unique mechanism
together with Omeros’ development of small-molecule inhibitors targeting
GPR174 could provide meaningful benefits over other cancer
immunotherapies and a significant advance for patients.”
Based on the collective data, small-molecule inhibitors of GPR174 could
provide a significant advance in cancer immunotherapy with meaningful
potential advantages over current cancer immunotherapies in development,
including CAR-T cell therapy and checkpoint inhibitors. Small molecules,
unlike antibodies, can be formulated for oral, intravenous,
intralesional and topical delivery, addressing some of the
administration and procedural limitations of other immunotherapies.
Small-molecule compounds, because of their shorter half-life than
antibodies, should not have the same safety concerns (e.g., acute,
life-threatening immune reactions due to extended duration of drug
activity) associated with CAR-T cell and checkpoint therapies. GPR174
inhibitors act on both CD4 (helper) and CD8 (cytotoxic) T-cells and
should not rely on the presence of specific tumor cell-surface receptors
to be effective as do checkpoint inhibitors. GPR174 inhibitors represent
a class of agents that could treat a broad range of cancers – the
primary mechanistic limitation of a GPR174 inhibitor is expected to be a
cancer cell that is recognized by the body’s immune system as fully
“self,” i.e., a cancer cell without mutation, which is quite rare.
“Omeros’ proprietary orphan GPCR program continues to generate new drug
targets, and GPR174 is one of our current areas of focus,” stated
Gregory A. Demopulos, M.D., chairman and chief executive officer of
Omeros Corporation. “The company’s development of GPR174 inhibitors and
related target-based intellectual property position expands our
therapeutic assets to oncology and, specifically, to the rapidly
progressing and high-interest field of cancer immunotherapy.”
About Omeros’ GPCR Program
Omeros uses its proprietary high-throughput CRA to identify
small-molecule agonists and antagonists for orphan GPCRs, or GPCRs
without known functionally active compounds (i.e., ligands),
unlocking them to drug development. Omeros believes that it is the first
to possess the capability to unlock orphan GPCRs in high-throughput, and
that currently there is no other comparable technology. Omeros has
screened a large number of orphan GPCRs against its small-molecule
chemical libraries using its proprietary, high-throughput CRA
technology. The CRA detects receptor antagonists, agonists and inverse
agonists. Omeros has identified and confirmed sets of compounds that
interact selectively with 54 of the 81 Class A orphan receptors linked
to metabolic, cardiovascular and immunologic disorders, oncology, and
disorders of the central nervous system. Omeros has also demonstrated
that the CRA is effective in identifying ligands for Class B GPCRs.
GPCRs, which mediate key physiological processes in the body, are one of
the most valuable families of drug targets. According to Insight Pharma
Reports, GPCR-targeting drugs represent 30 to 40 percent of marketed
pharmaceuticals. Examples include Claritin® (allergy), Zantac® (ulcers
and reflux), OxyContin® (pain), Lopressor® (high blood pressure),
Imitrex® (migraine headache), Reglan® (nausea) and Abilify®
(schizophrenia, bipolar disease and depression) as well as all other
antihistamines, opioids, alpha and beta blockers, and compounds acting
through serotonin and dopamine receptors.
The industry focuses its GPCR drug discovery efforts mostly on
non-sensory GPCRs. Of the 363 total non-sensory GPCRs, approximately 240
have known ligands with nearly half of those targeted either by marketed
drugs (46 GPCRs) or by drugs in development (about 82 GPCRs). There are
approximately 120 orphan GPCRs, which have no known ligands. Without a
known ligand, drug development for a given receptor is extremely
difficult.
About Omeros Corporation
Omeros is a biopharmaceutical company committed to discovering,
developing and commercializing both small-molecule and protein
therapeutics for large-market as well as orphan indications targeting
inflammation, coagulopathies and disorders of the central nervous
system. Part of its proprietary PharmacoSurgery® platform,
the company’s first drug product, OMIDRIA® (phenylephrine and
ketorolac injection) 1% / 0.3%, was broadly launched in the U.S. in
April 2015. OMIDRIA is the first and only FDA-approved drug (1) for use
during cataract surgery or intraocular lens (IOL) replacement to
maintain pupil size by preventing intraoperative miosis (pupil
constriction) and to reduce postoperative ocular pain and (2) that
contains an NSAID for intraocular use. In the European Union, the
European Commission has approved OMIDRIA for use in cataract surgery and
lens replacement procedures to maintain mydriasis (pupil dilation),
prevent miosis (pupil constriction), and to reduce postoperative eye
pain. Omeros has clinical-stage development programs focused on:
complement-associated thrombotic microangiopathies; complement-mediated
glomerulonephropathies; Huntington’s disease and cognitive impairment;
and addictive and compulsive disorders. In addition, Omeros has a
proprietary G protein-coupled receptor (GPCR) platform, which is making
available an unprecedented number of new GPCR drug targets and
corresponding compounds to the pharmaceutical industry for drug
development, and a platform used to generate antibodies.
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933 and Section 21E of
the Securities Exchange Act of 1934, which are subject to the “safe
harbor” created by those sections for such statements. All statements
other than statements of historical fact are forward-looking statements,
which are often indicated by terms such as “anticipate,” “believe,”
“could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,”
“may,” “plan,” “potential,” “predict,” “project,” “should,” “will,”
“would” and similar expressions and variations thereof. Forward-looking
statements are based on management’s beliefs and assumptions and on
information available to management only as of the date of this press
release. Omeros’ actual results could differ materially from those
anticipated in these forward-looking statements for many reasons,
including, without limitation, risks associated with product
commercialization and commercial operations, unproven preclinical and
clinical development activities, regulatory oversight, intellectual
property claims, competitive developments, litigation, and the risks,
uncertainties and other factors described under the heading “Risk
Factors” in the company’s Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission on November 9, 2016. Given these
risks, uncertainties and other factors, you should not place undue
reliance on these forward-looking statements, and the company assumes no
obligation to update these forward-looking statements, even if new
information becomes available in the future.
View source version on businesswire.com: http://www.businesswire.com/news/home/20161205005499/en/
Source: Omeros Corporation
Cook Williams Communications, Inc.
Jennifer Cook Williams
Investor
and Media Relations
360-668-3701
jennifer@cwcomm.org