By Jeff Kelley

Researchers at Virginia Commonwealth University could soon launch a clinical trial to test an intravenous solution that its inventor, a School of Medicine physiologist and surgery professor, says might treat massive blood loss in trauma patients.

Perfusion Medical Inc., a VCU startup working to commercialize the drug called PM-208, has received $1.8 million from the U.S. Air Force that moves the company a step closer to starting clinical trials.

“For a person who is bleeding out, PM-208 may take survival time from minutes to a day or more,” said Martin J. Mangino, Ph.D., a professor of surgery and of physiology and biophysics in the School of Medicine.

He is the co-founder of Perfusion, established in 2020 specifically to navigate the comprehensive process of moving a new drug through the Food and Drug Administration’s clinical trials process, which may take several years.

This past spring, Perfusion received a federal Small Business Innovation Research grant from the Air Force’s venture arm, AFWERX. Under terms of the award, Perfusion will work with the Air Force Research Laboratory’s human performance division and the 99th Medical Group to develop an investigational new drug application.

When it is accepted by FDA, Perfusion can begin Phase I clinical trials, which evaluate a drug’s safety in humans. The FDA requires any drug to go through multiple phases of clinical trials to determine safety and effectiveness, especially in comparison with current standards of treatment, before granting approval to use in medical settings.

“Our goal is to see this used worldwide, not only for severely injured soldiers on the battlefield but also by first responders and in hospitals, and for a wide range of conditions,” said Gerard Eldering, CEO of Perfusion. “PM-208 has a broad market that may save many lives, and we are working hard to get it into the hands of health care professionals who can make that happen.”

When a person is losing blood — think auto accident, gunshot and military combat — first responders treat the patient with intravenous solutions like whole blood or saline. The goal is to raise blood pressure and ensure there’s enough hemoglobin to transport oxygen through the body. Treatment isn’t always effective, and patients may suffer severe organ damage or die.

When cells can’t receive oxygen, they shut down and swell with water. That puts pressure on capillaries, which transport blood — and therefore, oxygen — to the body.

Perfusion’s PM-208 is given intravenously to the patient. Polyethylene glycol is the solution’s active ingredient — it attracts water, moving fluid out of swollen tissues and into blood vessels (capillaries) where it belongs, reducing pressure on capillaries and helping blood flow resume.

Mangino’s preclinical studies have found that PM-208 performs many times better than conventional approaches to improve recovery and survival from blood loss. Mangino is a co-author of several peer-reviewed studies in various medical journals.

After the FDA accepts the new drug application, the Perfusion-VCU-Air Force team will execute the Phase I clinical trial, with at least 25 healthy participants receiving the PM-208 solution intravenously.

Phase I looks primarily at safety. With statistical and safety results in hand, Perfusion plans to meet with FDA before proceeding with Phase II clinical trials, which could demonstrate clinical benefit in real-world human patients. In those trials, the solution would be used in appropriate trauma patients at VCU Health.

Though Mangino has participated in numerous clinical trials throughout his career, this is the first with his own drug. “This is a homegrown project at VCU,” he said. “We’re blazing new ground.”

The shock-therapeutics market has estimated annual revenue of over $4 billion, according to Perfusion. In addition to hemorrhagic shock, research suggests that PM-208’s biological mechanism of action could help patients experiencing other clinical events, including cardiac illness, critical illness, kidney injury and vascular disease.

In addition to the grant to aid clinical trials, AFWERX awarded Perfusion an additional $1.8 million to fund work on creating a smaller package for the drug, necessary for use in military field environments. The current development plan calls for PM-208 to be packaged in 500 milliliter intravenous bags for hospitals, but military medics operating under fire carry their own supplies and have asked for as portable bags as possible.

The AFWERX awards follow two others from the division in 2023 and come on top of a $2.9 million grant from the Defense Health Agency and more than $12 million awarded to VCU from the Department of Defense over the past decade.