On July 05, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that a recently published scientific article supports PharmaCyte’s ongoing research efforts that concern medical uses for constituents of Cannabis known as cannabinoids (Press release, PharmaCyte Biotech, JUL 5, 2016, View Source [SID:1234513713]). The article titled "Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids" was published in the journal, Aging and Mechanisms of Disease and appeared online on June 23, 2016. The article can be viewed in its entirety at View Source

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The Chief Executive Officer of PharmaCyte, Kenneth L. Waggoner, commented, "This research again demonstrates the potential benefit of cannabinoids in treating deadly and debilitating diseases such as cancer and neurodegenerative diseases. Our Cell-in-a-Box live-cell encapsulation technology provides a unique, versatile and natural platform for the delivery of potentially beneficial cannabinoids. It is PharmaCyte’s goal to use the combination of the Cell-in-a-Box technology and cannabinoids or cannabinoid-like compounds to develop effective and safe treatments for some of the deadliest forms of cancer for which such treatments do not presently exist, such as cancer of the pancreas, brain and breast, which affect hundreds of thousands of individuals worldwide every year."

The studies reported in the article, conducted by researchers at The Salk Institute for Biologic Studies and the University of California San Diego, showed that the inflammatory response initiated by "beta amyloid plaque" is blocked by cannabinoids. Beta amyloid plaque is an aggregating protein that has been linked to neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Accumulation of toxic beta amyloid plaque within nerve cells results in inflammation and nerve cell death. It is believed to be an early event in the development of many conditions associated with old age. The study showed that marijuana-derived cannabinoid molecules, such as tetrahydrocannabinol, stimulate the removal of beta amyloid plaque between neurons, block the inflammatory response and are thus protective against nerve cell death. This is the first study to show that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells. The implications are broad as there are currently no available drugs that significantly inhibit the cell death that is associated with these diseases.

On July 5, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported the publication of preclinical research in the journal Nature Medicine by the Company’s researchers and scientific collaborators (Press release, Verastem, JUL 5, 2016, View Source;p=RssLanding&cat=news&id=2181887 [SID:1234513711]). The research, which was led by David G. DeNardo, PhD, Assistant Professor of Medicine, Division of Oncology, Department of Immunology, Washington University School of Medicine in St. Louis, and co-author of the paper, demonstrated that focal adhesion kinase (FAK) inhibition decreases fibrosis and immunosuppressive cell populations in pancreatic ductal adenocarcinoma (PDAC), rendering previously unresponsive tumors sensitive to chemo- and immunotherapy.

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"The application of immunotherapy holds great promise to improve outcomes for patients with pancreatic cancer, as it has for melanoma and lung cancer patients," said Dr. DeNardo. "To date, however, attempts at immunotherapy in PDAC have achieved limited clinical benefit when deployed as single agents. This is likely due in part to the presence of a uniquely immunosuppressive tumor microenvironment which is dominant in most human cases of PDAC. Major drivers of this pro-tumorigenic microenvironment include a highly fibrotic stroma and extensive infiltration by immunosuppressive cell populations. Thus, agents that can potentially overcome excessive fibrosis while altering immune suppression would be particularly attractive targets for PDAC."

The paper, titled "Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy," (Jiang, et al., advanced online publication, July 4, 2016 (doi:10.1038/nm.4123) describes the therapeutic targeting of FAK in in vivo murine PDAC models. Prior research has demonstrated that hyperactivated FAK activity is a significant regulator of the fibrotic and immunosuppressive tumor microenvironment (TME) in PDAC tumor cells.

In this study, researchers show that FAK signaling is a key driver of fibrosis, immunosuppression and PDAC progression. It was then demonstrated that single-agent treatment with Verastem’s FAK inhibitor VS-4718 significantly limited tumor progression, resulting in a doubling of survival in an in vivo model of human PDAC. This slowing of tumor progression was associated with dramatically reduced tumor fibrosis, and a reduced number of tumor-infiltrating immunosuppressive cells. Given these findings, it was then hypothesized that the resulting effects of FAK inhibition on the TME may render PDAC tumors more sensitive to immunotherapy. Study results then demonstrated that FAK inhibition rendered previously unresponsive in vivo models responsive to T cell therapy and anti-PD1 antagonists. These data strongly support the ongoing clinical evaluation of FAK inhibitors in combination with checkpoint immunotherapy in patients with pancreatic cancer.

"FAK signaling has been shown to be important in several carcinomas, including pancreatic tumors, but its compelling role in creating an immunosuppressive tumor microenvironment is just emerging," said Jonathan Pachter, PhD, Chief Scientific Officer of Verastem, and co-author of the paper. "Another study, recently published in Cell, found that FAK inhibition can modulate certain immune cell populations, namely CD8+ T cells and Tregs, enabling an immune response that destroys tumors. Similarly, in the current study, we found that FAK inhibition alters tumor cell production of pro-inflammatory and immunosuppressive cytokines and reduces the tumor’s ability to avoid immune surveillance. Together these findings provide important support and rationale for the ongoing Phase 1 dose-escalation clinical study evaluating Verastem’s FAK inhibitor VS-6063 in combination with pembrolizumab and gemcitabine in patients with pancreatic cancer."

In early 2016, Verastem launched a new clinical development program focused on advancing its FAK inhibitors in combination with immuno-oncology agents and other current and emerging standard of care treatments. The Company’s lead FAK inhibitor, VS-6063 is currently being evaluated in a Phase 1 dose-escalation study at the Washington University in Saint Louis in combination with Merck & Co.’s PD-1 inhibitor pembrolizumab and gemcitabine in patients with pancreatic cancer. VS-6063 is also the subject of an additional clinical collaboration between Merck KGaA, Pfizer and Verastem where it will be evaluated in a Phase 1/1b study in combination with avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced ovarian cancer. This collaboration trial is expected to begin during the second half of 2016.

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. VS-6063 (defactinib) and VS-4718 are orally available compounds that are potent inhibitors of FAK. VS-6063 and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. VS-6063 and VS-4718 are currently being studied in multiple clinical trials for patients with cancer.

KB003 is a Humaneered, recombinant monoclonal antibody (mAb) that neutralizes soluble granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine for the growth of certain hematologic malignancies and solid tumors (Company Pipeline, KaloBios, JUL 4, 2016, View Source [SID:1234513679]).

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KB003 is a highly potent GM-CSF antagonist with a favorable safety profile that has previously been studied in more than 90 subjects in clinical studies in either healthy adults or adults with autoimmune diseases.

Data generated by a collaborator of the company confirm GM-CSF hypersensitivity plays an important role in inappropriate growth and survival of CMML cells, similar to juvenile myelomonocytic leukemia (JMML), in which such hypersensitivity is a hallmark of the disease.

This data also strongly suggests a role for KB003 in the treatment of CMML. Because KaloBios is now focused on oncology indications for KB003, and following discussions with clinical experts, the Food and Drug Administration, and the European Medicines Agency, the company intends to initiate study enrollment in a Phase 1 clinical trial in CMML patients to assess the safety, pharmacokinetics, and activity of KB003 in this patient population later this year.