The molecule found at VCU that powered a Wall Street transaction

By Jeff Kelley

When global powerhouse Bausch Health acquired a smaller biopharmaceutical company this month, the news marked a milestone in a journey that began at Virginia Commonwealth University nearly two decades ago.

Bausch estimates that alcohol-associated hepatitis is responsible for about 100 deaths per day in the United States and billions in health care costs. But the work of VCU's Shunlin Ren points to significant advances in treating the devastating condition and other liver disorders.

In 2006, Ren, M.D., Ph.D., professor in the Department of Internal Medicine at VCU's School of Medicine, along with colleagues at the Richmond VA Medical Center (formerly McGuire VA), began exploring how the body naturally regulates inflammation and cellular stress. Their efforts led to the identification of DUR-928, a naturally occurring small molecule known as a sulfated oxysterol.

By 2012, Ren was actively seeking industry partners to help move the compound into clinical development. After conversations with leaders at Durect Corp., the company's CEO flew to Washington to meet with Ren to discuss the molecule.

Within weeks, VCU TechTransfer and Ventures, which is part of the Office of the Vice President for Research and Innovation, entered into an exclusive licensing agreement with Durect. It granted the company rights to develop and commercialize DUR-928 and related compounds from Ren. Cupertino, Calif.-based Durect also committed to funding Ren's research program, which has amounted to several million dollars.

"Without that support, it would have been really difficult to keep the research going," Ren said.

Many patents and heavy potential

The collaboration proved highly productive: Ren and his partners have filed more than 70 international patents, including 12 in the United States, and they advanced DUR-928 through preclinical work, Phase 1 safety trials and Phase 2 clinical studies.

Bausch, which is publicly traded on the New York Stock Exchange, has now acquired Durect and refers to DUR-928 as Larsucosterol, which is designated for treating alcohol-associated hepatitis - a liver disease with few treatment options and high mortality rates. The compound has received both Fast Track and Breakthrough Therapy designations from the Food and Drug Administration, which expedites the review of drugs for serious conditions and those that show substantial improvement over available therapy.

The drug is also being investigated for MASH - metabolic dysfunction-associated steatohepatitis - and could have broader applications in metabolic and inflammatory diseases. Though Ren's research is not directly involved, his work is part of a broader mission underway at VCU through the nearly four-year-old Stravitz-Sanyal Institute for Liver Disease and Metabolic Health. The institute's goal is to find new ways to prevent, treat or reverse liver disease and help people all around the world to live longer, healthier lives.

"If successful, Larsucosterol could become the first FDA-approved therapy for alcohol-associated hepatitis," Ren said. "That would be a milestone with global implications, powered by discoveries made here at VCU."

Unlike traditional drugs that act on a single pathway, Larsucosterol functions as an epigenetic regulator. It can turn genes on or off without altering DNA sequence - and in doing so, restore cells, reduce damage and improve how organs function.

Early findings suggest Larsucosterol can reduce harmful inflammation, protect stressed cells from death and restore metabolic balance. A Phase 2b trial showed that treatment trended favorably for patients with alcohol-associated hepatitis compared with a placebo. While the study did not meet its primary endpoint of lowering mortality or need for liver transplant at 90 days, U.S. patients on the trial (a majority of the 307 patients) showed reductions in mortality. Faster treatment was associated with better outcomes, too.

Phase 3 trial and FDA review

Durect used a significant amount of cash in recent years and relied on outside funding and asset sales to support its operations. The acquisition by Bausch is expected to provide the financial backing needed to continue developing Larsucosterol.

Bausch plans a registrational Phase 3 clinical trial to evaluate the safety and efficacy of the drug - a randomized, double-blind, placebo-controlled, multicenter study to show 90-day survival rates. Ren is optimistic.

"If we can get FDA approval, then we should be on track to bringing this drug to market," he said.

For Ren, the experience has reinforced the value of partnering with industry.

"They support our research, we provide new indications to treat this disease and that disease," he said. "That's the way these partnerships should work."

For VCU, the partnership exemplifies a university's role in advancing discoveries from lab to market.

"By partnering with industry through clear licensing frameworks, universities can move promising molecules from bench to bedside, while supporting economic development and maintaining their role at the forefront of scientific innovation," said Magdalena Morgan, Ph.D., director of licensing at VCU TechTransfer and Ventures. "Shunlin and Durect, and now Bausch Health, is a great example of how a research collaboration can eventually bring patients a new hope never before thought possible."