Full Press Release Details
Discovery of Bispecific
Antibodies and Immune Checkpoint Inhibitors Which Kill Glioblastoma and Block the Metastasis of Malignant Melanoma Cells to the Lung
By Over 90% Announced by Ocean Biomedical and Aesther Healthcare (NASDAQ: AEHA)
Biomedical will be a wholly owned subsidiary of Aesther Healthcare Acquisition Corp. and will change its name to Ocean Biomedical,
Inc., expected to be listed on NASDAQ under the symbol, "OCEA".
RI and New York, NY, Sept. 6, 2022. Ocean Biomedical and Aesther Healthcare Acquisition Corp.("Aesther") (NASDAQ: AEHA)
announced today 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
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.
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
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
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.
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.
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 or 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.
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.
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 thousand of lives of people effected from NSCLC and GSM," said Dr.
Chirinjeev Kathuria, co-founder and Executive Chairman.
Ajjarapu, Chairman and CEO of Aesther, commented, "Aesther is honored to be part of the exciting discovery announced by Ocean Biomedical
today. We look forward to working with Ocean to bring these therapies to patients. This discovery and others will lead to long term shareholder
value growth and appreciation."
Aesther Healthcare Acquisitions Corp.
is a special purpose acquisition company (SPAC) formed for the purpose of effecting a merger, capital stock exchange, asset acquisition,
stock purchase, reorganization or similar business combination with one or more businesses. Its principals possess public and private
market investing experience and operational knowledge to bring value added benefits to Ocean Biomedical. The Aesther team has substantial
experience investing in and operating businesses in multiple sectors, as well as a significant long-term track record in creatively structuring
transactions to unlock and maximize value.
learn more, visit www.aestherhealthcarespac.com.
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.
learn more, visit www.oceanbiomedical.com
press release contains certain statements that are not historical facts and are forward-looking statements within the meaning of the
federal securities laws with respect to the proposed merger agreement between Aesther and Ocean Biomedical (the "Transaction"),
including without limitation statements regarding the anticipated benefits of the proposed Transaction, the anticipated timing of
the proposed Transaction, the implied enterprise value, future financial condition and performance of Ocean Biomedical and the combined
company after the closing and expected financial impacts of the proposed Transaction, the satisfaction of closing conditions to the proposed
Transaction, the level of redemptions of Aesther's public stockholders and the products and markets and expected future performance
and market opportunities of Ocean Biomedical. These forward-looking statements generally are identified by the words "believe,"
"project," "expect," "anticipate," "estimate," "intend," "think,"
"strategy," "future," "opportunity," "potential," "plan," "seeks,"
"may," "should," "will," "would," "will be," "will continue,"
"will likely result," and similar expressions, but the absence of these words does not mean that a statement is not forward-looking.
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.
announcement today is 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 provided for illustrative purposes only and are not intended to serve as, and must not be relied on 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. Many factors could cause actual future events to differ materially from the
forward-looking statements in this communication, including but not limited to: (i) the risk that the proposed Transaction may not be
completed in a timely manner or at all, which may adversely affect the price of Aesther's securities; (ii) the risk that the proposed
Transaction may not be completed by Aesther's business combination deadline; (iii) the failure to satisfy the conditions to the
consummation of the proposed Transaction, including the approval of the Merger Agreement by the stockholders of Aesther, the satisfaction
of the minimum net tangible assets and minimum cash at closing requirements and the receipt of certain governmental, regulatory and third
party approvals; (iv) the occurrence of any event, change or other circumstance that could give rise to the termination of the Merger