Microfabbed silicon as a (transformational) pharmaceutical material
Abstract:
Cancer remains the leading cause of death worldwide. The vast majority of cancer fatalities are owed to metastatic spread, dominantly to the lungs and liver. For these metastases, no cure is currently available, though multiple approaches can provide an extension of life expectancy typically of the order of weeks-to-months.
In preclinical animal models of cancer with involvement of lungs and liver, the use of microfabbed silicon components has yielded unprecedented results, which may provide an opportunity to develop a fully curative approach in human patients. In this presentation, I will review the key milestones of the path toward the currently approved clinical trial for ML-016, the lead multi-component therapeutic agent in the pipeline of BrYet US, Inc, specifically designed for primary and metastatic cancers of the lungs and liver, and the first-ever therapeutic agent with silicon microcomponents to reach the clinic. These milestones include preclinical data in different models of metastatic cancer, safety and toxicology data as required by regulatory agencies for the approval of clinical trials, drug design principles, and the manufacturing approaches, with emphasis on the silicon components of ML-016.
The unique advantage afforded by the silicon microparticle (“Si-Plateloid”) formulation in Bryet’s drugs is the ability for the therapeutic agent to target sequentially the key nodes of the cancer-associated molecular transport phenotype. This is largely invariant and indifferent to molecular subtypes of the cancer expressed in the target organ. By contrast, contemporary cancer therapeutics are based on the targeting of individual mutant or overexpressed molecules. Given that the mutational and molecular overexpression profile of cancer continues to evolve as the disease advances, the efficacy of molecule-level targeting approaches have invariably been limited by the emergence of therapeutic resistance – the fundamental reason why metastatic disease has been incurable to date.
In this scenario, the key role played by the Si-Plateloids is to mimic the behavior of blood platelets, concentrating on the vascular endothelium of microvessels associated with tumors, and facilitating the penetration into the tumor microenvironment of therapeutic agents (a peptide-drug conjugate, in the case of ML-016) with the selective capability to reach and eliminate otherwise therapy-resistant cancer cells.
Biography:
Mauro Ferrari currently serves as President and CEO of BrYet US, dedicated to creating novel therapies approaches against cancer, which comprise micro/nanofabbed silicon componentry. He has been a member of the Board of Directors of Arrowhead Pharmaceuticals (NASDAQ:ARWR) since 2010, and is an affiliate professor of pharmaceutics at the University of Washington in Seattle. He previously served as President and CEO of Houston Methodist Research Institute, Executive Vice President of the Houston Methodist Hospital, professor of materials science and engineering at the University of California Berkeley, professor of medicine and engineering at The Ohio State University, and professor/chairman at the University of Texas Medical School and MD Anderson Cancer in Houston Texas. His civil service included Special Advisor and Eminent Scholar at the National Cancer Institute, and President of the European Research Council of the European Union. He has published extensively and received numerous awards from the US and internationally.