As previously announced, Ocean Biomedical, Inc. (NASDAQ: OCEA)
celebrates the discovery of
bispecific antibodies
that target Chitinase 3-like-1 and immune checkpoint inhibitors,
killing glioblastoma cells and melanoma cells,
and blocking the metastasis of malignant melanoma
cells to the lung by over 90%. Glioblastoma multiforme
(GBM) is a deadly type of brain tumor and 5-year survival is just
8% for those aged 45-54. About 25% of GBM patients are not actively
treated due to rapid disease progression. Malignant melanoma, the
most serious skin cancer, can metastasize to other organs. Once it
has spread to other organs it is difficult to treat. Metastatic
melanoma (Stage IV) has 22.5% five year survival. Non-small cell
lung cancer (NSCLC) is a major unmet medical need that accounts for
85% of pulmonary malignancies and effects approximately 450,000
individuals. In greater than 50% of affected patients the tumors
are diagnosed at advanced stages with metastatic spread that
precludes curative surgical resection.
Background
Recent studies of NSCLC have highlighted genetic
abnormalities that underlie these tumors. These genetic
abnormalities generate abnormal proteins that have not been
previously seen by the patient’s immune system which, in turn,
activates antitumor immune responses that control tumor initiation
and progression. Studies over recent years have demonstrated that
tumor initiation and progression are often mediated by the ability
of the tumors to produce immunosuppressive proteins and activate
immunosuppressive pathways, called immune checkpoint inhibitors
(ICPI), that allow tumor growth and progression by shutting off
these critical anti-tumor immune responses. This includes the
programed death (PD) pathway including PD-1, PD ligand 1 (PD-L1)
and PD-L2 and the cytotoxic T-lymphocyte-associated protein 4
(CTLA4) pathway that includes CTLA4 and its binding partners
B7.1/B7.2. Antibodies that target ICPI such as PD-1, PD-L1 and
CTLA4 have been generated which have therapeutic efficacy in NSCLC
and other tumors. Unfortunately, only a minority of patients
respond to these therapies and the responses are often not
durable.
Chitinase 3-like-1 (CHI3L1) is a member of the
18 glycosyl hydrolase gene family that is readily detected in the
circulation of normal individuals and expressed at exaggerated
levels in the circulation of individuals with diseases
characterized by inflammation, tissue remodeling and or
cancers.
Discoveries
Recent studies from our laboratory have
demonstrated that CHI3L1 is a critical regulator of a number of key
cancer-causing pathways. We have highlighted its ability to inhibit
tumor cell death (apoptosis), its inhibition of the expression of
the tumor suppressors P53 and PTEN and its stimulation of the B-RAF
protooncogene. Most recently we have discovered that CHI3L1 is a
“master regulator” of ICPI including key elements of the PD-1 and
CTLA4 pathways. In accord with the importance of these pathways we
have also generated antibodies: 1.) a monoclonal antibody
against CHI3L1, and 2.) bispecific antibodies that
simultaneously target CHI3L1 and PD-1 or CTLA4. The
impressive ability of our bispecific antibodies to control primary
and metastatic lung cancer in murine experimental modeling systems
is discussed below.
We generated bispecific antibodies
that simultaneously target CHI3L1 and PD-1 or
CTLA4. We then compared their effects in experimental
models in which T cells and tumor cells are cultured together (a
co-culture system) and in a murine model of lung metastasis. In all
cases we compared the effects of the bispecific antibody to control
antibodies, and to individual monospecific antibodies against
CHI3L1, PD-1 or CTLA4, alone or in combination and the results are
shown in the figures below.
In the coculture system, critical immune
regulating cells called T cells were placed in culture with cancer
cells. The ability of the antibodies to induce T cell
differentiation and kill (induce apoptosis) of the tumor cells were
then evaluated. As can be seen in Figure 1 below, tumor cell death
was not induced by isotype control antibodies, and modest degrees
of tumor cell apoptosis were seen in cultures with monospecific
antiCHI3L1, antiPD-1 or antiCTLA4 individually. Additive tumor cell
death was seen when antiCHI3L1 was administered in combination with
antiPD-1 or and CTLA4 alone. Most importantly, highly impressive
synergistic tumor cell death was seen when the cocultures were
treated with the bispecific antibodies (FRGxCTLA4 or FRGxPD-1). In
all cases the cell death that was induced was due to T cell
differentiation into CD8+ cytotoxic T cells.
In the murine metastasis model we administered
malignant melanoma cells into the murine circulation and evaluated
their spread to the lungs and pleural surface by counting the
number of black staining pleural metastasis. Tumor metastasis were
readily appreciated in lungs from mice treated with isotype control
antibodies, and modest decreases in metastasis were seen in lungs
from mice treated with monospecific antiCHI3L1, antiPD-1 or
antiCTLA4 individually. Additive inhibition of tumor spread was
seen when antiCHI3L1 was administered in combination with antiPD-1
and CTLA4. Most importantly, highly impressive synergistic
inhibition of tumor metastasis was seen in lungs from mice treated
with the bispecific antibodies (FRGxCTLA4 or FRGxPD-1). Figure 2
below shows the results with the FRGxCTLA4 antibody.
Quoted
“Bispecific antibodies that simultaneously
target CHI3L1 and ICPI like PD-1 and or CTLA4 have an impressive
and synergic ability to induce tumor cell death and prevent tumor
metastasis compared to individual antibody moieties,” commented Dr.
Jack A. Elias, Dean Emeritus of Medicine and Biological Sciences
and Professor of Translational Science, Medicine and Molecular
Microbiology and Immunology at the Warren Alpert Medical School
Brown University; Scientific co-founder.
“Non-small cell lung cancer (NSCLC) is the
leading cause of cancer death and second most diagnosed cancer in
the US. Glioblastoma multiforme (GBM) is a lethal type of brain
tumor that affects approximately 28,000 people in the U.S. The
median survival time is about 15 months. With our discovery that
CHI3L1 is a critical regulator of a number of key cancer-causing
pathways by highlighting its ability to inhibit tumor cell death
(apoptosis) this therapy has the potential to save thousands of
lives of people effected from NSCLC and GBM,” said Dr. Chirinjeev
Kathuria, co-founder and Executive Chairman.
Suren Ajjarapu, one of Ocean’s Directors
commented, “Ocean is proud to be advancing this exciting discovery
and we look forward to bringing these therapies to patients. This
discovery and others will lead to long term shareholder value
growth and appreciation.”
About Ocean Biomedical
Ocean Biomedical, Inc. is a Providence, Rhode
Island-based biopharma company with an innovative business model
that accelerates the development and commercialization of
scientifically compelling assets from research universities and
medical centers. Ocean Biomedical deploys the funding and expertise
to move new therapeutic candidates efficiently from the laboratory
to the clinic, to the world. Ocean Biomedical is currently
developing five promising discoveries that have the potential to
achieve life-changing outcomes in lung cancer, brain cancer,
pulmonary fibrosis, and the prevention and treatment of malaria.
The Ocean Biomedical team is working on solving some of the world’s
toughest problems, for the people who need it most.
To learn more, visit www.oceanbiomedical.com
Forward-Looking Statements
The information included herein and in any oral
statements made in connection herewith include “forward-looking
statements” within the meaning of the “safe harbor” provisions of
the United States Private Securities Litigation Reform Act of 1995.
Forward-looking statements may be identified by the use of words
such as “estimate,” “plan,” “project,” “forecast,” “intend,”
“will,” “expect,” “anticipate,” “believe,” “seek,” “target” or
other similar expressions that predict or indicate future events or
trends or that are not statements of historical matters, although
not all forward-looking statements contain such identifying words.
These forward-looking statements include, but are not limited to,
statements regarding estimates and forecasts of financial and
performance metrics and expectations. These statements are based on
various assumptions, whether or not identified herein, and on the
current expectations of the Company’s management and are not
predictions of actual performance. These forward-looking statements
are provided for illustrative purposes only and are not intended to
serve as, and must not be relied on by any investor as, a
guarantee, an assurance, a prediction or a definitive statement of
fact or probability. Actual events and circumstances are difficult
or impossible to predict and will differ from assumptions.
The announced discoveries were based solely on
laboratory and animal studies. Ocean Biomedical has not conducted
any studies that show similar efficacy or safety in humans. There
can be no assurances that this treatment will prove safe or
effective in humans, and that any clinical benefits of this
treatment is subject to clinical trials and ultimate approval of
its use in patients by the FDA. Such approval, if granted, could be
years away.
Forward-looking statements are predictions,
projections and other statements about future events that are based
on current expectations and assumptions and, as a result, are
subject to risks and uncertainties. These forward-looking
statements are not guarantees of future performance, conditions or
results, and involve a number of known and unknown risks,
uncertainties, assumptions and other important factors, many of
which are outside the control of the Company that could cause
actual results or outcomes to differ materially from those
discussed in the forward-looking statements. Important factors,
among others, that may affect actual results or outcomes include
(i) the outcome of any legal proceedings that may be instituted
against the Company; (ii) changes in the markets in which the
Company competes, including with respect to its competitive
landscape, technology evolution, or regulatory changes; (iii)
changes in domestic and global general economic conditions; (iv)
risk that the Company may not be able to execute its growth
strategies; (v) risks related to the ongoing COVID-19 pandemic and
response, including supply chain disruptions; (vi) risk that the
Company may not be able to develop and maintain effective internal
controls; (vii) the risk that the Company may fail to keep pace
with rapid technological developments to provide new and innovative
products and services or make substantial investments in
unsuccessful new products and services; (viii) the ability to
develop, license or acquire new therapeutics; (ix) the risk that
the Company will need to raise additional capital to execute its
business plan, which may not be available on acceptable terms or at
all; (x) the risk that the Company experiences difficulties in
managing its growth and expanding operations; (xi) the risk of
product liability or regulatory lawsuits or proceedings relating to
the Company’s business; (xii) the risk of cyber security or foreign
exchange losses; (xiii) the risk that the Company is unable to
secure or protect its intellectual property.
The foregoing list of factors is not exhaustive.
You should carefully consider the foregoing factors and the other
risks and uncertainties that are described in the Company’s Annual
Report on Form 10-K for the year ended December 31, 2021 and its
Quarterly Report on Form 10-Q for the quarter ended September 30,
2022, and which are described in the “Risk Factors” section of the
Company’s definitive proxy statement filed by the Company on
January 12, 2023, and other documents to be filed by the Company
from time to time with the SEC and which are and will be available
at www.sec.gov. These filings identify and address other important
risks and uncertainties that could cause actual events and results
to differ materially from those contained in the forward-looking
statements. Forward-looking statements speak only as of the date
they are made. Readers are cautioned not to put undue reliance on
forward-looking statements, These forward-looking statements should
not be relied upon as representing the Company’s assessments as of
any date subsequent to the date of this filing. Accordingly, undue
reliance should not be placed upon the forward-looking
statements.
Ocean Biomedical Media RelationsSean
LeousSean.Leous@westwicke.com
Kevin KertscherCommunications Director
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