NIH Funds Hingez Therapeutics to Develop New Cholesterol Pill

Tuesday, September 18, 2018 General News
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Hingez's Approach May Lead to Better Solutions for Treating High-Cholesterol, Other Diseases

WASHINGTON, Sept. 18, 2018 /PRNewswire-PRWeb/ -- In August, Hingez Therapeutics Inc. received a grant totaling more than

1.8 million from the National Institutes of Health (NIH) to develop oral drugs to treat high cholesterol, with the goal of reaching human trials within two to three years.

"Hingez Therapeutics is using molecular simulations to discover an orally deliverable small molecule to disrupt disease protein-protein interactions; this has the potential to be developed as a new drug for the treatment of high-cholesterol and for other new drug discovery opportunities," said Ahmed A. Hasan, MD, PhD, FACC, FAHA, and medical officer and program director at the NIH's National Heart, Lung, and Blood Institute (NHLBI).

The body manufactures cholesterol, a waxy, fat-like substance that has important natural functions, contributing to brain and hormone function and vitamin storage. Though the body manufactures all the cholesterol that it needs, cholesterol can also be taken into the body through saturated fats found in animal products such as egg yolks, meat and cheese and from trans fats found in some commercially baked cookies and crackers. There is a good type of cholesterol known as high-density lipoproteins (HDL) that carries cholesterol from around the body back to the liver for cleansing from the body. Low-density lipoproteins (LDL) are the 'bad' cholesterol that leads to a buildup of plaque in the arteries, leading to risks of stroke and heart attack. More than 102 million American adults have cholesterol levels above healthy levels and more than 35 million Americans have cholesterol levels that put them at risk for heart disease. The Center for Disease Control has made September into National Cholesterol Education Month to raise awareness around food choices and to advocate for blood tests.

While a healthy diet and exercise can help some who suffer from high-cholesterol, others may need medication. Statins are often prescribed, but for some patients, these drugs may cause side effects or may not be sufficient. A new class of injectable drugs such as Repatha has been developed to treat patients where Statins are insufficient. Humanized antibodies such as Repatha bind to and inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9), which blocks liver cell receptors from removing LDL cholesterol from the body. However, injectable medications can be difficult, expensive (up to $14,000 a year), and cumbersome (self-injected every two weeks). For chronic diseases such as hypercholesteremia (high cholesterol), treatment lasts for decades, creating high costs that may result in non-compliance; this creates significant barriers for patients and the healthcare system.

Hingez Therapeutics Inc. was funded the 1.8 million dollar grant (grant number 2 R44 HL134462-02) in August to develop small molecule inhibitors of PCSK9 through the NHLBI's Small Business Program that supports research and development by US-owned and operated small businesses on innovative and commercially-promising products to prevent, diagnose, and treat heart, lung, and blood-related diseases and disorders. Hingez Therapeutics' small molecule inhibitors are being developed as a pill alternative to the effective but expensive and injectable PCSK9 antibodies. Such an agent could be globally manufactured with a reasonable price tag, easily administered as an oral therapeutic, and it could have the potential to gain a sizable share of a large lipid lowering drug market.

Hingez Therapeutics Inc., identifies flexible regions inside of a protein using powerful supercomputers to select stable conformational trajectories that are unable to participate in disease causing protein-to-protein interactions when engaged with a small molecule drug. Hingez Therapeutics' approach is akin to identifying a door hinge (a flexible region of a protein) that could be jammed with a tiny nail (drug molecule) to restrict opening and closing of a door (PPI interface conformations).

Hingez Therapeutics, Inc. is perhaps the only company in the world that focuses on conformational changes to a flexible area of a protein to stabilize the specific conformations with small molecules, and consequently allosterically disrupt protein-protein interactions. Flexible areas are not visible in crystalline structures and molecular dynamic simulations are a preferred technique to study them. But molecular dynamic simulations require a huge amount of computing power. As a small business, Hingez Therapeutics has access to large computing power including at the Oak Ridge National Laboratory that houses the world's fastest supercomputer.

This project by Hingez Therapeutics, Inc., has great implications for general drug discovery and human diseases. There are about 20,000 genes in the human genome that make about 18,000 proteins yet, out of these 18,000 proteins, less than 1,000 proteins are targeted for all the FDA-approved pharmaceutical products on the market today as most drugs are targeting the rigid areas of a protein. Hingez Therapeutics is unlocking the potential to discover drugs that utilize the 95 percent of remaining proteins that are not targeted in today's disease treatments. Inappropriate protein-protein interactions or lack thereof cause a large number of diseases in humans including cancer, neurological and cardio-renal disorders. If protein-protein interactions can be manipulated via small drug molecules, it will catapult drug discovery into a new era of development of therapeutics for diseases that have none today.

"We have developed a revolutionary small molecule drug discovery method that will produce oral medications to treat high cholesterol and eventually many other diseases," said Dr. Salim Shah, principal investigator on the grant, founder and president of Hingez Therapeutics Inc. "I truly believe that we are advancing medical science around the Second Law of Thermodynamics and as such, we are opening new doors to whole new advances in drug discovery and disease treatment. We greatly appreciate the support of the National Institute of Health. We look forward to creating collaborations with major pharmaceutical companies and academic institutions to further develop PCSK9 small molecule inhibitors, to targeting others disease causing protein-protein interactions, and to helping millions of Americans suffering from high-cholesterol and other diseases by bringing new drugs to market."

 

SOURCE Hingez Therapeutics



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