Serendipity And CDMO Catapult COVID-19 Candidate

By Louis Garguilo, Chief Editor, Outsourced Pharma

This gets filed in the scientific realm of:

“Hey, look what we might have here? Can you believe it?”

A key ingredient for advanced, oral-solid-dose opioid medicines in phase one and two, developed and manufactured with assistance from a CDMO, turns out to have investigative potential for the treatment of COVID-19.

And with another intervention of Fortuna, the ingredient has been stockpiled.

The contract development and manufacturing partner, Recro Pharma, Inc. of Gainsville, GA, immediately creates a work plan to develop that ingredient – nafamostat (nafamostat mesylate; a synthetic serine protease inhibitor]– as a stand-alone clinical candidate for biopharma Ensysce.

 

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Before CEO Lynn Kirkpatrick can catch her breath, Ensysce Biosciences has a coronavirus candidate in the clinic.

“And we didn’t even have to change CDMOs to run in the new direction,” she says.

Oral Nafamostat For COVID-19

As described in an earlier editorial, Enscyse is a biopharma requiring some time to unwrap.

Kirkpatrick explains this new development:

“We’ve had a massive amount of activity in such a short time. We already had two [opioid] candidates in the clinic. Then we find out one of the ingredients we’re using for our prescription drug overdose protection platform is beneficial for COVID. Who would have thought?

Ensysce quickly decides to apply for emergency use, files and receives an IND, and starts a clinical trial within a matter of six months.”

That trial for oral nafamostat was completed in November of 2020, and is progressing to phase 2 in COVID-19 patients that are not hospitalized, yet without therapeutic options.

“Our primary mission is to change analgesic care,” continues Kirkpatrick, “but when we became aware our starting material nafamostat  appeared to have utility against coronaviruses, we quickly commenced clinical studies with our oral formulation.”

Ensysce formed a subsidiary, Covistat, Inc., to focus on the use of oral nafamostat for the treatment of COVID-19.

Nafamostat has been widely used intravenously in Asia. It is approved in Japan for pancreatitis and other diseases. (It is not approved in the U.S.)

Ensysce believes it’s new product will have important utility in an outpatient setting, or where vaccines cannot be readily accessed, and at low cost.

The drug has a novel mechanism of action for treating COVID-19, as a potent protease inhibitor that blocks SARS-CoV-2 viral entry into host cells. “We believe nafamostat, taken by mouth, could dramatically change treatment options,” says Kirkpatrick.

“People newly infected with the virus may be able to use it outside of hospitals. Our current expectation is that the medication could keep the disease from progressing, and prevent unnecessary hospitalizations.”

Nafamostat is a component of Ensysce’s multi-pill abuse resistance (TAAP™ and MPAR™) platform, currently in clinical trials – “A major clinical milestone for the protection of opioid overdose,” says the company.

The “Aha” Moment

As the coronavirus was spreading worldwide, Kirkpatrick and her business development officer, Richard Wright, started exploring clinical trials being undertaken for COVID-19.

Nafamostat popped up on the list.

With further investigation into the science behind the molecule, they hypothesized how effective nafamostat might be for all coronaviral infections.

But there was an immediate concern.

Numerous companies chasing down materials for COVID-19-related drug development were reporting material scarcities or complete unattainability, and rising prices for any available materials.  

“That was the thing,” Kirkpatrick tells me, “as we uncover all this activity and potential, we realize we have 5 kilos of the clinical grade material on hand, because we are using it for a different purpose.

“And we continue to work with our CDMO to source even more. But we can get through our trials as is.”

Now with the phase one study under their belt, Ensysce is working with Recro to get drug product ready for the next studies. With material available, and a proposal in place, the CDMO is primed to develop and manufacture the new product for clinical testing.

“Being an established client enabled us to fit into their workflow in order to meet our timeline. Despite some limits on capacity, they facilited our needs by exploring options to get our project started as quickly as possible,” Kirkpatrick commented.

“Actually,” she adds, “we’ve had calls from all over the world for this material.”

“Vaccines alone will not solve the ongoing mutations of this virus, and we’ve got a potentially valuable resource – in effect, a low-cost, repositioned small-molecule that has a healthy shelf life.” 

Pills Not Vaccines

Kirkpatrick and Ensysce/Covistat certainly aren’t the only ones thinking in terms of pills vs. vaccines.

Former FDA commissioner Scott Gottlieb recently said of the continuing coronavirus battle:

“The real solution is a pill you can take like an aspirin.”

Ensysce is now in a race to make that statement a reality as much as an analogy. Pfizer and others are on the small-molecule trail as well. No doubt more competition is on the way.

But thanks to forward-leaning leadership, the ability to make quick decisions, some serendipity and a solid CDMO partnership, Ensysce may be ahead of the pack.

“And with a quality working relationship with an outsourcing partner, we are looking to make a difference in the lives of many people.”