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Adipo Therapeutics: Advancing the Treatment of Obesity and Other Related Metabolic Disorders Through the Power of Brown Fat and Increased Energy Expenditure



Adipo Therapeutics is in late preclinical development of a novel obesity treatment with the mission of bringing healthy weight loss through the power of brown fat and increased energy expenditure for millions of people seeking to manage their weight beyond dieting alone.  Adipo’s leadership team, including CEO Karen Wurster, brings an average of 30 years of experience in developing and launching blockbuster pharmaceuticals, and quickly recognized the potential benefits of increasing brown fat with this unique treatment for people living with obesity.  Karen Wurster and founder Meng Deng, Ph.D., have brought together a team with deep scientific, regulatory, medical, manufacturing expertise to make this vision a reality.

 

Brown fat (BAT) is a recognized target for the treatment of obesity and metabolic disease.  BAT is naturally occurring in small amounts in all mammals, including people, and higher levels of BAT are associated with physiologic benefits including increased energy expenditure, improved insulin resistance, and decreased cardiovascular risk. In retrospective studies, individuals with higher levels of BAT had lower prevalence of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, these findings highlight a potential role for BAT in promoting cardiometabolic health. (Nature Medicine January 2021; 58–65).  The natural plasticity between white fat and BAT provides an opportunity to create additional BAT, with even minor increases providing potential therapeutic benefits associated with the higher levels of BAT. 

 

Adipo’s lead product, ADPO-002NP creates small subcutaneous brown fat depots by leveraging this natural plasticity. Adipo uses Notch-inhibiting PLGA nanoparticles to induce mitochondrial biogenesis in subcutaneous white fat, thus “browning” the white fat to create small subcutaneous BAT depots to act as energy-burning lipid sinks, decreasing body weight, glucose, and circulating lipids. ADPO-002NP Notch-inhibiting PLGA nanoparticles are designed specifically to provide rapid uptake into white fat cells, low dose, sustained intra-cellular drug delivery, and limited biodistribution. The amount of weight loss is dependent on the amount of BAT created, with an estimate of 1/3 pound of new BAT providing 25 pounds of weight loss over 12 months. Given the metabolic benefits of BAT, the benefits of ADPO-002NP treatment are likely to extend beyond weight loss to include improvements in glucose, lipids and cardiovascular health associated with higher levels of BAT. This approach has the potential to bring unique benefits for healthy weight loss for people who want to lose weight without losing the enjoyment of food, who need to maintain healthy nutrient intake, and who have lowered resting metabolic rate due to metabolic adaptation or age.

 

Preclinical studies of the treatment of animals and adult human fat tissue with ADPO-002NP have shown promising results. Animal studies with weekly treatment of ADPO-002NP, have demonstrated increasing local, subcutaneous brown fat leads to weight loss, improved blood glucose, and decrease in lipids with no change in calorie intake (C. Jiang et al. Frontiers in Endocrinology 2015; Molecular Therapy 2017).   Excitingly, the potential to brown human fat has been recently demonstrated through studies of treatment of in-vitro human fat cell culture and ex-vivo human white fat tissue with ADPO-002 providing support for human translation of this mechanism of action. These data will be presented at the American Diabetes Association meeting in Orlando, Florida on June 23rd during an oral session entitled "Novel Modulators of Adipose Tissue Function and Adiposity."

 

ADPO-002NP is being developed as an orthogonal treatment to currently available anti-obesity medicines (e.g, GLP1s) for patients seeking weight loss beyond diet alone.  Current obesity treatments act primarily through calorie restriction which can lead to slowing resting metabolic rate, metabolic adaptation, making sustained weight loss through those methods difficult while also depriving the body of vital nutrients needed to maintain muscle mass and healthy body composition. Adipo acts differently, with an orthogonal approach of increasing energy expenditure using local delivery to limit off target impacts and side effects.  

 

Adipo’s leadership team is led by Karen Wurster, CEO of Adipo, who brings over 25 years of experience working as a pharmaceutical executive where she has developed and launched multiple blockbusters for diabetes.  Adipo’s Scientific Founder is Meng Deng, Ph.D., Associate Professor of Biological Engineering, Biomedical Engineering, and Materials Engineering at the top ranked Purdue University, with a B.E. in Chemical Engineering from Tsinghua University, China, a Ph.D. in Chemical Engineering from the University of Virginia and postdoctoral research at the University of Connecticut Health Center and the MIT Langer lab.  Adipo’s experienced leadership team also includes Keith Johns, former Sr. VP, Eli Lilly Global Diabetes and Obesity, Matthew Sheetz, MD, Ph.D., as Medical Advisor, and Roger Miller, as VP of Manufacturing Operations. The team shares the drive to deliver on the mission for the 100 million people in the U.S. living with obesity by advancing the management of their disease via increasing the calories their body burns.   

Company Contact Information:

Karen Wurster, CEO

phone: 317-292-7414

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