- BioAegis Therapeutics believes that its lead product, recombinant human plasma gelsolin therapy (rhu-pGSN), is a viable therapeutic option for patients suffering from severe lung injury due to Covid-19.
- The private clinical stage company is awaiting FDA approval to accelerate their clinical trial of plasma gelsolin therapy on Covid-19 patients.
- BioAegis discovered plasma gelsolin — an abundant, naturally occurring circulating protein found in the human body's immune system — nearly two decades ago.
- The company has built a portfolio of therapies around this unique anti-inflammatory to treat a wide range of conditions, including influenza, pneumonia, arthritis, Alzheimer's, lupus, inflammatory bowel disease and multiple sclerosis.
For one little-known biotech company in New Jersey — BioAegis Therapeutics — Covid-19 may just be the catalyst that will push its breakthrough discovery, plasma gelsolin, to the forefront as a lifesaving treatment for infectious, inflammatory and degenerative diseases.
Discovered nearly two decades ago in a Harvard lab by the late Dr. Thomas Stossel, a professor of medicine at Harvard Medical School and head of translational medicine at Brigham and Women's Hospital in Boston, plasma gelsolin is an abundant, naturally occurring circulating protein found in the human body's immune system.
According to Stossel, it is "a master regulator of the immune system." In a wide range of diseases, it balances the inflammatory process without suppressing the immune system, thus preventing severe consequences and greatly improving survival.
To focus on developing therapies for infectious, inflammatory and degenerative diseases through a portfolio built around plasma gelsolin (pGSN) therapeutics, Stossel co-founded BioAegis in 2011 and became chief scientific advisor to his clinical stage biotech company.
For nine years the scientists at BioAegis have been studying this unique anti-inflammatory and its effect on treating a wide range of conditions, including influenza, pneumonia, arthritis, Alzheimer's, lupus, inflammatory bowel disease, multiple sclerosis and more.
What they discovered was that plasma gelsolin is depleted in severe inflammatory conditions and that restoring a recombinant human form of plasma gelsolin in the body has enormous potential to prevent the lethal ravages of inflammation, such as those caused by Covid-19.
"We've been studying this exact same condition — not with this particular virus, but with severe flu, severe pneumonia — for years, so we feel like we are in the perfect position to treat this disease," said BioAegis CEO Dr. Susan Levinson.
BioAegis said plasma gelsolin, its lead product, addresses the underserved severe community-acquired pneumonia market, with projected peak sales of $5 billion. Additional products for multiple acute and degenerative target diseases represent $50 billion in pipeline opportunities.
To date the private clinical stage company has raised more than $20 million through a network of family offices and wealthy individuals, as well as non-dilutive funding, and currently holds 50 patents issued for coverage of infection, inflammatory disease, renal failure, multiple sclerosis and other neurologic diseases.
They have collaborated with over 20 institutions worldwide, including the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Harvard T.H. Chan School of Public Health, Harvard-Brigham & Women's Hospital, Massachusetts General, Weill Cornell Medical Center, Mount Sinai Beth Israel, Vanderbilt School of Medicine and University of Pennsylvania.
BioAegis had just conducted its Phase 1b/2a clinical trial last year in hospitalized pneumonia patients and was gearing up to raise the $30 million needed to conduct Phase 2 testing of its plasma gelsolin therapy on patients with severe pneumonia when Covid-19 hit.
"Suddenly we needed to pull out all the stops," said Levinson. From individual backers and family offices, the company raised several million dollars in a special bridge financing, said Levinson. "No venture firm or big institution is in the race yet. That's going to be our next round. Covid-19 happened, so we decided to do this bridge and just get the money as fast as we could."
Now the company is awaiting FDA and multicountry regulatory approval to start Phase 2 trials of its plasma gelsolin therapy on Covid-19 patients.
Although the FDA responded to BioAegis' inquiry after just one week and other regulators have been very responsive, Levinson admits she is concerned that being a small company means she needs to push harder.
"We are this little company, and nobody really knows about us," she says. "The companies that you hear about — GlaxoSmithKline, Roche, Novartis — all the big players have lots of visibility. They are selling drugs already, they have lots of funding, and they are able to do a lot more than a little company like us, with 11 people. How can we compete with companies with 50,000 people and billions of dollars in sales?"
Gilead Sciences spent $50 million on the research and development of its antiviral drug remdesivir during the first quarter, it disclosed in its earnings report Thursday. The company said it will spend as much as $1 billion for the year.
Other big players are partnering up to study treatments — Regeneron Pharmaceuticals and Sanofi are working on a drug called Kevzara; Roche and Chugai Pharmaceutical are studying Actemra — and each have healthy financial backing.
Yet Levinson is still hopeful: "There's something like 200 applications that have been filed to the FDA for products for Covid-19. "These run the gamut from vaccines to repurposed drugs that might be antiviral, to brand-new concepts just starting down the path. We have a product that has already been tested in pneumonia patients."
Since 2015, BioAegis has generated data in several models of pneumonia and most recently published a paper on severe influenza entitled "Delayed administration of recombinant plasma gelsolin improves survival in a murine model of severe influenza."
"We looked at the gene transmission that occurs when you give gelsolin to the animals that have flu, and it shows how it down-regulates genes for the kinds of mediators that cause a cytokine storm, which is exactly what happens in Covid -19, and it up-regulates genes that lead to healing," Levinson says. Additionally, it's been shown to protect the lungs from damage.
Because BioAegis' recombinant human plasma gelsolin has been manufactured to be identical to the natural human protein, it is not expected to result in serious side effects when supplementing the depleted protein. BioAegis confirmed that no safety signals were seen when it conducted its Phase 1b/2a clinical trial last year in hospitalized pneumonia patients, animal toxicology studies or prior human studies when dosed either intravenously or by inhalation.
"We looked at three different doses of the drug, thinking that with the highest one there might be side effects and we would have to back off. But it turns out that at that highest dose, there were no side effects. It actually raised the levels of gelsolin way above normal, and still there were no side effects," said Levinson.
She added that the trial also revealed how long the gelsolin lasts in the bloodstream: "We could dose once a day and there was still plenty of drug around," she said.
On Saturday the U.S. Department of Health and Human Services said it would allow state health departments to start distributing Gilead Sciences' remdesivir globally to hospitals. The United States will receive about 40% of the drug maker's donation — approximately 607,000 vials.
The pharmaceutical company received emergency use authorization from the FDA on May 1 after preliminary data from a clinical trial showed remdesivir moderately reduced the recovery time of patients hospitalized with severe Covid-19.
But on April 29 former FDA Commissioner Scott Gottlieb told Becky Quick on CNBC's "Squawk Box" that remdesivir "is not a home-run cure by any means, but I think that this can be very effective in the context of better treatment for patients, a better understanding of how to treat these patients, and hopefully other drugs are going to come on to the market. This is part of the better toolbox we've been talking about."
As far as comparing plasma gelsolin to remdesivir, Levinson says they each play a completely different role in treating Covid-19 and that perhaps the BioAegis therapy could be looked at as something that could be used in conjunction with the Gilead drug.
"Remdesivir is an antiviral, so it's trying to remove the virus before things get out of control. What is missing from that is addressing the overexuberant inflammatory response that the body often uses to get rid of the virus. So I think if you treat people early enough before that overexuberant inflammation has started, then the remdesivir will be helpful. But once that inflammatory response has gotten out of control, I don't think the remdesivir is going to work. You're going to need something else," she says.
Dr. Steven M. Opal, an infectious disease specialist at Alpert Medical School of Brown University in Providence Rhode Island, is a medical advisor for BioAegis. He agrees that remdesivir would be much more effective if used with an anti-inflammatory.
"Remdesivir, which is an antiviral drug, has shown efficacy by shortening the duration of illness in a Phase 3 human trial. There is still significant need for agents which modulate the host immune response, such as recombinant human plasma gelsolin, which could have additive effects and significantly improve survival rates," he told CNBC.
Dr. Mark DiNubile, BioAegis' chief medical officer and infectious disease expert, further explained that plasma gelsolin plays a central regulatory role in diverse inflammatory pathways and that a dual-pronged attack on Covid-19 concurrently — with remdesivir or another antiviral agent — will reduce the virus and quell the inflammatory tsunami, shutting down the Covid-19 attack better than either modality alone.
"Plasma gelsolin is for the most serious Covid-19 patient. Remdesivir is shortening the disease by getting rid of the virus faster. But where gelsolin plays, where people are in the hospital, they have trouble breathing — it's at that real serious point — so when we are testing gelsolin, we will be testing to save lives," said Levinson.
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