ASGCT Annual Meeting 2024

Bio: Alex Goraltchouk is the Chief Operating Officer at Remedium Bio with broad functional responsibilities overseeing development, technical operations, manufacturing, and supply chain for viral and non-viral vector gene therapies. Prior to Remedium, Alex held roles of increasing responsibilities with a focus on Operations and R&D at companies ranging from start-ups to Fortune 500, including Allergan, Biogen, and Regeneron. Alex holds a Bachelor's in Materials and Master's in Chemical Engineering from the University of Toronto, an MBA and Master of Science in Finance from Indiana University, and a Master of Science in Microbiology and Cell Sciences from the University of Florida. He is a Cornell certified Six-Sigma/Lean black belt, holds a MicroMasters in Supply Chain Management from MIT, and a MicroMasters in Bioinformatics from the University of Maryland Global Campus. Alex is an author of close to 200 patents, patent applications, peer-reviewed scientific publications, and abstracts with a focus on biotechnology and advanced therapeutic modalities.

Abstract: Gene therapies have revolutionized medicine by enabling durable, curative treatments for a number of genetic diseases. Unfortunately, they remain largely relegated to the treatment of rare, monogenic conditions due to their high cost, immunogenicity, and inability to adjust the dose following initial administration. Recombinant protein treatments enable dose adjustment, but require repeat, often lifelong treatment regimens, and are challenged by pharmacokinetic sawtoothing, which limits safety at the peaks and efficacy at the troughs. To overcome these challenges, Remedium developed the first adjustable-dose gene therapy system, Prometheus™ - for subcutaneous administration of adipocyte-targeted, non-integrating genetic cassettes, in a low-cost, non-antigenic manner. The system enables durable transgene expression with zero-order pharmacokinetics, remaining local to the subcutis while secreting therapeutic protein in the same locale where it would otherwise be delivered by a series or repeat injections. Using IVIS bioluminescent reporter transgene imaging, we confirmed that expression was durable over the full study duration (6 months), predictably up-titratable via redosing, and down-titratable by a number of physical (cryolipolysis) and pharmacological (iCasp9 suicide gene) techniques. We confirmed the system to be highly localized to the subcutaneous injection area (>99.6% based on assayed tissues), with predominant targeting of adipocytes and no detectable involvement of the liver, spleen, heart, or kidneys. The Prometheus™ system was used to administer GLP-1 and Exenatide (EX4) to mice with diet-induced diabetes and obesity. Prometheus™-delivered GLP-1-DNA and EX4-DNA treatments produced 20% and 14% weight loss at 4 weeks relative to vehicle control. Fasting glucose levels were reduced by 37% and 38% for GLP-1- and EX4-treated animals, relative to high-fat diet, diabetic mice. Insulin sensitivity was enhanced as evidenced by a 25% and 22% area under curve (AUC) reduction on the insulin tolerance test (ITT). Similarly, the glycemic response was improved as evidenced by 29% and 26% AUC reductions on the glucose tolerance test (GTT) for GLP-1- and EX4-treated animals, respectively. The treatments were well tolerated locally and systemically as confirmed by the absence of injection site reactions and systemic biomarkers of inflammation, liver function, and muscle injury. In summary, we report the development of the first, adjustable-dose gene therapy platform technology and its potential application for the treatment of type 2 diabetes and obesity.