Impacting obesity: an enormous health concern impacting over 650 million people worldwide with serious health consequences
Cyta Therapeutics, Inc. (Cyta) is a pre-clinical stage therapeutics company based on a novel chemistry platform developed in the laboratory of Professor S. Thayumanavan at the University of Massachusetts, Amherst. Cyta is building a pipeline of products based on a novel class of polymer-based nanogels, called IntelliGels. The company’s lead development program is a therapeutic (Cyta-001) to treat obesity and other metabolic conditions such as NASH, type 2 diabetes and high cholesterol. Cyta-001 is a liver-targeted IntelliGel in which a potent thyromimetic drug has been non-covalently encapsulated inside the polymer. Recent data by Cyta and Professor Thayumanavan’s laboratory shows dosing of Cyta-001 in diet-induced obese (DIO) mice leads to complete reversal of body weight gain in treated animals; reductions were also observed in a number of altered metabolic parameters, including fatty liver, elevated cholesterol and triglycerides, insulin resistance and high liver enzyme levels (ALT, AST).
Disruption of metabolism regulation leads to several debilitating diseases such as obesity, inflammatory liver steatosis such as NASH, type 2 diabetes, and hyperlipidemia. In particular, the rise in obesity in the US population is at epidemic proportions with over 42% of adults considered obese (BMI between 30 - 35). The increase in obesity is directly related to the increase in a variety of chronic medical conditions, such as cardiovascular disease, stroke, type 2 diabetes and increased cancer risk. The estimated annual medical cost of obesity in the United States was nearly $173 billion in 20191.
Cyta is interested in collaborating with potential partners to further develop its lead program and also leverage its delivery platform as a solution to improve therapeutic index for particular drug assets.
Cyta’s lead product candidate, Cyta-001, is a thyroid hormone receptor β (TRβ) agonist that is encapsulated inside a liver-targeted, polymeric nanoparticle. Our technology platform, called IntelliGel, consists of polymeric subunits that self-assemble and non-covalently encapsulate our highly potent and hydrophobic TRβ agonist. In order to target liver hepatocytes, an anionic functionality is attached to the external surface of the IntelliGel nanoparticle which binds to the organic anion-transporting polypeptide (OATP) receptor. The OATP receptor is highly expressed in hepatocytes and mediates uptake of organic ions into the liver.
Once inside the hepatocyte, due to high levels of glutathione, the polymer disassembles, and the TRβ agonist drug is released intracellularly and is able to activate the TRβ receptor. LEARN MORE >
Cyta-001 was tested in the diet-induced obesity mouse model since thyromimetics are known to positively impact fat metabolism and cholesterol levels. Mice were fed a high fat diet for 24 weeks and subsequently dosed for 5 weeks with Cyta-001 (as well as controls) to evaluate physiological, biochemical and histopathological endpoints. The results show that Cyta-001 led to a complete reversal of body weight vs control animals. There was no change in the body weight of mice dosed with the blank IntelliGel and mice dosed with drug alone were not able to achieve the same level of body weight loss as Cyta-001. LEARN MORE >
Our recent poster at the 6th Obesity and NASH Drug Development Summit in Boston, MA shows additional results observed upon treatment of DIO mice with Cyta-001; this includes marked reduction of liver fat, cholesterol, triglycerides and reversal of ALT/AST elevation. Serum T4 is not changed with treatment with Cyta-001, showing that the thyromimetic is not systemically available and is acting through the liver. T4 level is however significantly decreased in the TRβ alone dose, showing some systemic exposure.
Our pipeline will be generated from our IntelliGel drug delivery platform.
Team & Advisors
Bernadette (Bonnie) C. Fendrock, MS, MBA
Chief Executive Officer, founder
Ms. Fendrock was CEO and Co-founder of Hepregen Corporation, a venture backed, commercial stage, MIT spin-out based on the bioengineered in vitro micro-liver platform developed by Professor Sangeeta Bhatia. In her more than 25 years of life science industry experience, Ms. Fendrock has held leadership roles in general management, corporate and business development, marketing and program management working at foundational biotechnology companies including Genzyme, Somatix (one of the first gene therapy companies), Genetics Institute and Acusphere. Prior to receiving her MBA, she worked in research and product development at Integrated Genetics and Centocor. Her technology experience includes biotherapeutics, gene therapy, biological medical devices, bioengineered tools and chemistry-based delivery platforms. In 2012, Ms. Fendrock was honored along with other innovation leaders as one of the Mass High Tech ‘Women to Watch’. Ms. Fendrock is on the Board of Wellspring House and also is a member of the Commercial Advisory Board of the Gloucester Marine Genomics Institute (GMGI). She received a B.A. in Molecular Biology from Wellesley College, a MS in Interdisciplinary Science from MIT and a MBA from The Wharton School, University of Pennsylvania with a Fellowship in Management of Technology.
W. Stephen (Steve) Faraci, Ph.D.
Chief Scientific Officer, founder
Prior to Cyta Therapeutics, Dr. Faraci was Executive Director and Site Head at Capsugel’s Product Development Center with a focus on formulation development and clinical manufacturing. Previously, Dr. Faraci worked for over 23 years at Pfizer Global Research & Development in a variety of leadership roles throughout the organization. He was a founding member of the leadership team that helped build a new R&D site in Cambridge, MA in 1999, growing from 10 employees to over 150. He had various leadership roles at the site, including Head of Biology, Interim Site Head and Chief Operating Officer. His responsibilities included internal research and development as well as external academic/industry collaborations. Steve was a member of the Mass Biotech Council Board of Directors. He received his Ph.D. in Chemistry from Wesleyan University and continued his training as a National Institute of Health Postdoctoral Fellow at the Massachusetts Institute of Technology and Harvard Medical School in the laboratory of Professor Christopher Walsh.
Roman Herrera, Ph.D.
Head of Preclinical Development
Dr. Herrera obtained his Ph.D. in Molecular Pharmacology at Albert Einstein Medical College studying the structure-function relationship of the insulin receptor. After Post-doctoral training at the Dana Farber Cancer Institute, studying genes linked to cell differentiation, he joined (1992-2011) Parke-Davis/Warner Lambert-Pfizer (Ann Arbor, MI/Cambridge/MA) where he worked in drug discovery programs across several disease areas such as inflammation, diabetes and cancer. He assumed increased leadership roles in target identification/validation, in vivo disease models and biomarkers strategies to support both pre-clinical and clinical (Phase I/II) programs. Prior to joining Cyta, he was a consultant to biopharmaceutical and biotech startup companies.
Scientific & Clinical Advisors
S. (Thai) Thayumanavan
Distinguished Professor, Departments of Chemistry and Biomedical Engineering, University of Massachusetts Amherst, Director of the Center for Bioactive Delivery, Institute for Applied Life Sciences
Chair of SAB, Inventor of Cyta Technology, co-founder
Dr. S. “Thai” Thayumanavan is a leader in the design and syntheses of new macromolecules, especially polymers, to obtain responsive supramolecular nanoassemblies. These responsive nanoassemblies are being pursued for applications in the delivery of small molecules and biologics, in addition to imaging and diagnostics applications. His work has resulted in more than 180 peer-reviewed publications in high-impact journals. The innovation in his work has also produced numerous patents. Dr. Thayumanavan has received a multitude of national and international recognitions for his creative contributions, including election as a fellow of the American Association for the Advancement of Science (AAAS), the CRSI Medal by the Chemical Research of India, and the Chancellor’s Medal by UMass. Dr. Thayumanavan received his early education from The American College in Madurai, India. He received his Ph.D. from the University of Illinois at Urbana-Champaign. Following a postdoctoral stint at Caltech, he started his independent career at Tulane University in 1999 and joined the faculty at UMass Amherst in 2003.
Benjamin Cravatt, Ph.D.
Professor, Skaggs Institute for Chemical Biology and Chair, Department of Chemical Physiology at The Scripps Research Institute
Dr. Cravatt’s research group is interested in understanding the roles that enzymes play in physiological and pathological processes. To address this challenge, they develop and apply an array of genetic, pharmacological, and proteomic/metabolomic technologies. The Cravatt group has obtained fundamental insights into the chemical, biochemical, and physiological workings of several important mammalian serine hydrolases. Dr. Cravatt obtained his undergraduate education at Stanford University, receiving a B.S. in the Biological Sciences and a B.A. in History. He then trained with Drs. Dale Boger and Richard Lerner and received a Ph.D. in Macromolecular and Cellular Structure and Chemistry from The Scripps Research Institute (TSRI) in 1996. Professor Cravatt joined the faculty at TSRI in 1997 as a member of the Skaggs Institute for Chemical Biology and the departments of Cell Biology and Chemistry. Dr. Cravatt is a co-founder and scientific advisor of Activx Biosciences, Abide Therapeutics and Vividion Therapeutics. His honors include a Searle Scholar Award (1998-2001), the Eli Lilly Award in Biological Chemistry (2004), a Cope Scholar Award (2005), the Irving Sigal Young Investigator Award (2007), the Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry (2008), a MERIT award from the National Cancer Institute (2009) and inducted member of the National Academy of Sciences (2014) as well as being elected as a member of the American Academy of Arts and Sciences (2016).
Thomas S. Scanlan, Ph.D.
Professor of Chemical Physiology and Biochemistry, School of Medicine
Director, Program in Chemical Biology
Graduate Program in Biomedical Sciences, School of Medicine
Dr. Scanlan is a professor of physiology and pharmacology, and director of the Program in Chemical Biology at the OHSU School of Medicine in Portland, Oregon. Prior to joining OHSU, he served as professor of chemistry, pharmaceutical chemistry and cellular and molecular pharmacology at the University of California, San Francisco from 1991 to 2006. Dr. Scanlan’s research focuses on the chemistry, physiology and medicine of thyroid hormone action. He is an internationally recognized leader in the field of thyroid endocrinology and the creation of novel thyroid hormone analogs and testing them in disease models is a central component of his research. Dr. Scanlan’s laboratory discovered and characterized thyromimetic agonists such as sobetirome, thyroid hormone antagonists, and a novel class of biogenic amine thyroid hormone metabolites. Dr. Scanlan’s laboratory recently devised a prodrug strategy for targeting thyromimetics to the central nervous system for the treatment of neurodegenerative diseases. He was a founder of Serra Pharmaceuticals, a nuclear receptor therapeutics company acquired by Karo Bio, AB. He was also a founder of the thyromimetic therapeutics companies EndoChem and NeuroVia, focused on developing thyromimetic treatments for metabolic disease and an inborn error of metabolism called X-linked adrenoleukodystrophy. Dr. Scanlan has authored more than 180 scientific publications and is an inventor on 17 issued patents. Dr. Scanlan holds a Ph.D. in chemistry from Stanford University and a B.S. in chemistry from the University of Oregon.
Gyongi Szabo, MD, Ph.D.
Chief Academic Officer of Beth Israel Lahey Health
Chief Academic Officer of Beth Israel Deaconess Medical Center (BIDMC)
As Chief Academic Officer of Beth Israel Lahey Health, Dr. Gyongyi Szabo oversees the system's robust research and teaching programs. In this role, Dr. Szabo works with research and academic leaders across the system to amplify our collective academic impact by fostering coordination and collaboration across institutions; aligning research and education priorities while honoring our commitments to our existing academic partners; establishing common capabilities and infrastructure; and attracting and retaining world-class researchers and educators, supported by exceptional administrative teams.
Dr. Szabo also serves as Chief Academic Officer of Beth Israel Deaconess Medical Center (BIDMC), where she oversees BIDMC's robust research and teaching programs and identifies and supports a broad range of basic, translational and clinical research priorities.
An internationally recognized leader in the field of liver immunology and a highly regarded educator, Dr. Szabo brings extensive knowledge and experience in scientific research and mentorship. Most recently, she served as Vice Chair for Research in the Department of Medicine, Associate Dean for Clinical and Translational Sciences, Director of the MD/PhD Medical Scientist Training Program and Associate Vice Provost for Interprofessional Education in Research at the University of Massachusetts Medical School.
Having published more than 200 peer-reviewed journal articles, Dr. Szabo leads a research laboratory focusing on cures for liver inflammation. She is a fellow of several professional associations, including the American Gastroenterological Association, the American College of Physicians, and the American Association for the Study of Liver Diseases, where she served as President in 2015. She is a recipient of Doctor Honoris Causa from the Semmelweis University and elected member of the Hungarian Academy of Sciences.
She earned her medical degree at the University Medical School in Debrecen, Hungary and her doctoral degree from the Hungarian Academy of Sciences.