Boosting Brown Fat to Combat Obesity and Type 2 Diabetes

Eat less. Exercise more. It sounds so simple. But if it were that simple, America wouldn’t be facing the dual epidemics of obesity and diabetes.

Adipo Therapeutics, a Purdue Research Foundation-backed startup, is developing a unique treatment approach that turns bad fat into good fat. This disruptive nanotherapeutic delivery could provide a safe and effective way to treat obesity and Type 2 diabetes.

Nearly 42% of all adults in the United States are clinically obese. And obesity is driving a Type 2 diabetes epidemic, impacting over 30 million people in the U.S. Treatment of obesity and its related conditions — including heart disease, strokes, Type 2 diabetes and certain types of cancer — amount to a staggering $173 billion in U.S. medical costs annually, according to the Centers for Disease Control. Not to mention the tremendous loss of life — obesity-related conditions are among the leading causes of preventable, premature death, resulting in an eight-year reduction in life expectancy. 

The biggest misconception about obesity? That it all boils down to willpower. If people just tried harder, they could lose weight. Not necessarily so, says Frank Greenway, MD, chief medical officer at the Pennington Biomedical Research Center at Louisiana State University and one of the nation’s leading experts on the treatment of obesity.

“Obesity is a chronic disease,” Dr. Greenway says. “Like all chronic diseases, there are factors contributing to obesity that are controlled physiologically. Much like hypertension, there’s a limit to what behavioral changes can achieve in the long-term. Just as a physician might prescribe medication to help control blood pressure, sometimes medication is also needed to help control weight.”

The leading medications to treat obesity and diabetes work by suppressing a patient’s appetite, decreasing the number of calories they consume. With some of these drugs providing patients 15% to 20% weight loss, these new obesity treatments are expected to greatly increase the number of people with obesity seeking medically approved, reimbursed treatment. These medications also improve glucose by increasing the amount of insulin released in the body. Yet even these treatments are not enough. The majority of people receiving treatment for diabetes are not reaching their weight or blood sugar goals.

But what if there were a medication that targeted the other side of the equation? One that increased the calories burned and improved insulin resistance by increasing the body’s own beneficial brown fat (brown adipose tissue)?

“A drug that increased metabolic rates could be combined with another medication that suppressed appetite,” Dr. Greenway says. “The advantage is that each treatment works through a different mechanism. So the results would be additive.”

And the impact on the nation’s health would be tremendous. It’s not exactly a magic bullet for weight loss and diabetes, but it is a promising new medication under development at Adipo Therapeutics.

A revolutionary approach to weight loss and Type 2 diabetes

Meng Deng, PhD, didn’t set out to change the way obesity and Type 2 diabetes are treated. The associate professor of agricultural and biological engineering, biomedical engineering and materials engineering at Purdue University merely wanted to apply his research interest in engineering cell-instructive biomaterials to help people. He began talking with medical experts around the country and those conversations yielded a recurring theme: there is an unmet clinical need for the treatment of obesity and its related diseases, particularly Type 2 diabetes.

“I realized there was an opportunity to leverage technology to tackle the problem in a different way,” Dr. Deng says. “By harnessing the power of native physiology we can increase energy expenditure with higher amounts of energy-burning brown fat.”

The audacious endeavor built upon the interdisciplinary collaborative work at Purdue. He partnered with Shihuan Kuang, PhD, professor of animal sciences at Purdue University, to form an interdisciplinary team encompassing the fields of biomaterials science, micro/nanoengineering, cell biology and translational medicine to develop a platform technology of Notch-inhibiting nanoparticles.

The cells in our bodies use Notch signaling pathways to communicate. The technology Dr. Deng and Dr. Kuang developed involves injecting Notch-inhibiting nanoparticles into subcutaneous white fat — the dominant type of fat in our bodies that stores energy and increases weight — and signaling those cells to convert to energy-burning brown fat.

The process, called browning, can be targeted to specific areas of the body thanks to the nanoparticles which enable precise delivery of the drug to the targeted cells. Only after the nanoparticles enter the white fat cells is the drug released, minimizing potential side effects. The nanoparticles are engineered to release the drug over the course of a week through a self-administered injection.

Deng founded Adipo Therapeutics to commercialize the technology through the Purdue Research Foundation Office of Technology Commercialization. Backed by the Purdue Startup Foundry, a startup incubator on the university’s West Lafayette campus, Adipo is poised to implement clinical trials as soon as the company finalizes its investigational new drug (IND) application with the U.S. Food and Drug Administration.

“There’s a saying in the drug development industry that you have to cross the ‘valley of death’ to move from a lab discovery to an effective treatment for patients,” Deng says. “Translational research requires a village to bridge the gap between preclinical studies and clinical trials. Adipo has a professional team with the necessary expertise in research and development, business and manufacturing as we continue to navigate the journey from bench to bedside.”

A deep bench of expertise

In her decades working at Eli Lilly and Co. on treatments for Type 2 diabetes, pharmaceutical executive Karen Wurster developed a strong empathy for the patients.

“Diabetes can be such a devastating disease as it progresses,” Wurster says. “About half of all Type 2 diabetes patients aren’t meeting their therapeutic goals. It’s a disease state intertwined with obesity, so there’s often a lot of shame and self-blame among the patients.”

Wurster, who has a background in biochemistry and business, was part of the team that launched the first GLP-1 receptor agonist, a class of Type 2 diabetes and obesity medications that improve blood sugar control and may also lead to weight loss. GLP-1 is now a $10 billion product category. It was only one of 10 diabetes products Wurster launched throughout her career.

She thought she was ready for retirement, until she learned about Dr. Deng’s vision for Adipo Therapeutics. She’s now CEO for the company, spearheading its business efforts, leading a cross-functional team, establishing financing and cultivating potential strategic partners.

“I have a deep understanding of the market and what it takes to develop a product, moving it through the FDA approval process to a successful launch,” Wurster says. “There’s something really exciting about the opportunity to run that play again to bring another first-in-class treatment to patients.”

Wurster’s industry connections helped secure other essential team members, including Roger Miller, vice president of operations. Miller’s extensive experience in the pharmaceutical industry and biotech startups ensures Adipo will meet the stringent FDA standards for manufacturing.

“Roger brings a strong focus in quality control,” Wurster says. “Before we even opened the lab, he made sure we were operating according to FDA standards, something a lot of other startups companies or academic labs aren’t necessarily incorporating. He evaluated our contract manufacturing organizations and led them through the rigorous process to provide consistent materials for both our active ingredient and our final drug product.”      

An investment opportunity

It was only relatively recently, in June 2013, that the American Medical Association voted to recognize obesity as a disease state requiring treatment and prevention efforts. A 2022 report issued by Morgan Stanley noted the immense potential for market growth among medications to treat obesity.

“Though more than 650 million people globally are clinically obese, only about 7% are diagnosed and recommended for medical treatment. By contrast, other chronic conditions, such as diabetes, have 80% to 90% treatment rates,” states the report, which predicts 25% of obese adults will use medicine to actively manage their weight by 2035.

Adipo’s current funding partners include Elevate Ventures, Purdue Ventures, Indiana University Ventures and Vision Tech.

While the concept of browning is gaining momentum in the industry, Dr. Deng’s novel technology of Notch-inhibiting nanoparticle delivery is a game changer for realizing the potential impact of treating obesity.

“Because of Adipo’s mechanism of action, we have a unique opportunity not just to demonstrate the safety of delivery but also the process of browning,’ Wurster says. “Through our phase 1 clinical trials, we could be the first to show clinical proof of browning in people.

“I’ve worked in the pharmaceutical industry, specifically diabetes management, for my entire career. To be able to bring forward a brand new mechanism of action that will help a great many people diagnosed with Type 2 diabetes and obesity, it’s incredibly thrilling to lead the team that will move this groundbreaking science into the market.” 

To date, Adipo Therapeutics has raised a total of $2.8M seed funding. The company is now raising a bridge to its Series A financing round.

Read the original article on GlobeNewswire.