Univ. Spin-Off Developing Long-Lasting Diabetes Drug

(kalhh, Pixabay. https://pixabay.com/illustrations/bathroom-scale-libra-weight-control-1149264/)

25 June 2018. A company spun-off from a University at Buffalo biochemistry lab is the recipient of a small business grant to design a once-a-week drug for people with type 2 diabetes to control their blood sugar and weight. Transira Therapeutics, in Getzville, New York, is receiving a $224,000 award from National Institute of Diabetes and Digestive and Kidney Diseases, or NIDDK, part of National Institutes of Health.

Transira Therapeutics is developing and commercializing work from the lab of Buffalo biochemistry professor Qing Lin, also the company’s founder. Lin and colleagues study peptide-based therapeutics. including interactions of these short chains of amino acids with other proteins and their effects on cellular processes. Because of their simple chemistry, peptides are often potent in the lab and do not cause toxic reactions, but they also are unstable and inefficient when working with living cells. Thus one of the the Lin lab’s objectives is to assemble peptides into larger and more stable chains that capture the potency and safety of peptides, while enhancing their stability so they can be given as drugs.

The company’s first product is a treatment for type 2 diabetes, in a long-acting synthetic protein. Diabetes is a chronic disorder where the pancreas does not create enough insulin to process the sugar glucose to flow into the blood stream and cells for energy in the body. In type 2 diabetes, which accounts for at least 90 percent of all diabetes cases, the pancreas produces some but not enough insulin, or the body cannot process insulin. Centers for Disease Control and Prevention says diabetes affects 30.3 million people in the U.S., with the number of people with the disease tripling in the past 20 years as the population ages and becomes overweight. Diabetes is also the 7th leading cause of death, and leading cause of kidney failure, lower-limb amputations, and adult-onset blindness.

Lin and colleagues from Buffalo and California Institute for Biomedical Research in La Jolla designed a synthetic form of the hormone oxyntomodulin. In the body, oxyntomodulin helps increase insulin production, as well as encourages the body to increase its expenditure of energy and reduce food intake. But like peptides, oxyntomodulin breaks down quickly in the body, making it impractical to be taken in its natural state.

The researchers devised a synthetic version of oxyntomodulin that adds a stabilizing amino acid called cysteine to different parts of the hormone’s chemistry, and link the parts together to keep the hormone’s components in their original configuration. In preclinical research, the team’s synthetic oxyntomodulin analogs help lab mice reduce their blood glucose levels, but are also more stable and last longer in the body than the natural hormone.

The NIDDK grant is an early-stage Small Business Innovation Research or SBIR award to Transira for a 1-year project to further develop this synthetic oxyntomodulin into a long-lasting injectable drug. “With injectable drugs,” says Lin in a university statement, “you don’t want to ask people to use them too often because they may sometimes forget or skip a dose because they are not in a setting that’s convenient to make an injection. That’s why a longer-lasting therapy is so important.”

The synthetic hormone aims to decrease fasting blood glucose levels by at least 25 percent and reduce the weight of diet-induced obese mice by 20 percent or more. The drug would also be injected under the skin and last for the equivalent of a week in the test mice. If this first stage is successful, the company would then apply for further SBIR funds to advance the synthetic hormone through chemical activity and toxicology tests to the point of clinical trials.

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