Ocean Biomedical, Inc. (OCEA). Ocean Biomedical’s Scientific Co-founder, Dr. Jack A. Elias, MD, presented details of his previously published discoveries that have potential application for tumor suppression across multiple cancer pathways at the Legorreta Cancer Center’s recent meeting in Providence. In his talk, Dr. Elias focused on his lab’s groundbreaking work on understanding the development and progression of lung cancer, especially the role of Chitinase 3-like-1 (CHI3L1). He also shared details of his novel therapeutic discoveries that show the efficacy of monospecific and bispecific antibodies against CHI3L1 and PD-1 as therapies for non-small cell lung cancer, and glioblastoma multiforme. Ocean Biomedical is currently working to move these antibody therapeutic discoveries towards Phase 1 clinical trials.
In his recent talk, Dr. Elias shared details of his team’s discoveries of the role CHI3L1 in regulating primary and metastatic lung cancer, glioblastoma multiforme, and broader oncogenic pathways. He discussed the inverse correlation of circulating CHI3L1 with prognosis for disease progression and survival, and the step-by-step experimentation done to create effective monospecific antibodies, and then a powerful bispecific antibody that has a multiplicative effect on reducing tumor by triggering tumor apoptosis in metastatic melanoma, glioblastoma, and non-small cell lung cancer.
In his talk, Dr. Elias additionally shared the potential for extending the regulation of this “master anti-tumor pathway” to other cancers, and promising research that reveals an additional anti-tumor pathway targeting T-cell co-stimulation using the inducible co-stimulator (ICOS) and its ligand ICOSL, and Cluster of Differentiation 28 (CD28) and its ligands B7-1 and B7-2. The Methods and Compositions patents that have been granted to Dr. Elias for these mono-specific and bi-specific antibody approaches have been granted for use in multiple cancer types, including Prostate Cancer, Colon Cancer, Rectal Cancer, Ovarian Cancer, Kidney Cancer, Breast Cancer, Glioblastoma, Melanoma, Malignant Melanoma, and Lung Cancer.
Dr. Elias, who is the former Chair of Yale’s Department of Medicine, and the Dean Emeritus of Medicine and Biological Sciences at Brown University summed up his team’s work saying, “It was great to share the details of our work with colleagues at the Legorreta Cancer Center. In narrowing in on major pathways that are applicable across cancer types, we believe we are making discoveries that will drive treatment and patient outcomes forward. Realizing that if you control CHI3L1, you don’t just control one anti-cancer pathway, you simultaneously control many anti-cancer pathways is an unprecedented leap forward and we are very pleased to be accelerating this research with Ocean Biomedical.”
“We are excited to see the reactions to Dr. Elias's discoveries that CHI3L1 is a critical regulator of T-cell activity. These therapies have the potential to save lives of people affected not just by lung metastasis, and melanoma, but also non-small cell lung cancer, glioblastoma and other forms of cancer,” said Dr. Chirinjeev Kathuria, co-founder and Executive Chairman.
Malignant melanoma, a very serious skin cancer with a 22.5% five-year survival for patients with Stage IV disease, can metastasize to other organs. Once it has spread to other organs, it is difficult to treat – in some cases, it can spread to the lungs and result in non-small cell lung cancer (NSCLC), a major unmet medical need that accounts for 85% of pulmonary malignancies and affects approximately 450,000 individuals. In over 50% of affected NSCLC patients, tumors are not diagnosed until the advanced stages, with metastatic spread that precludes curative surgical resection.
Recent studies of NSCLC have highlighted the effectiveness of immune checkpoint inhibitor (ICPI), therapies that block cancer-proliferating proteins like CHI3L1 and help the patient’s body recognize and attack cancer cells. Unfortunately, only a minority of patients respond to these therapies and the responses are often not durable.
Recent studies from Ocean Biomedical have demonstrated that CHI3L1 is a critical regulator of a number of key cancer-causing pathways, highlighting 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 Dr. Elias’s research team has 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, Ocean has also generated antibodies: 1.) a monoclonal antibody against CHI3L1, 2.) bispecific antibodies that simultaneously target CHI3L1 and PD-1, and 3.) a new bispecific antibody that simultaneously targets CHI3L1 and CTLA4. The impressive ability of these bispecific antibodies to control primary and metastatic lung cancer in murine experimental modeling systems have been discussed in detail in an earlier article in the Journal of Clinical Investigation, and this expanded approach in Frontiers in Immunology.
Suren Ajjarapu, a Director of Ocean Biomedical commented, “Immunotherapy is the future of cancer care, and we are proud to be partnering with Dr. Elias in advancing the development of his cancer treatments, along with his fibrosis treatments, and our global malaria program. We look forward to bringing all of these therapies to patients as Ocean Biomedical moves forward, for the long-term shareholder value and the continued advancement of medical science.”