If Ensysce Biosciences were a ball of yarn, we’d be unwinding it for hundreds of miles from its location in La Jolla, California.
Solid oral dose programs, when biologics and advanced therapies are all the rage
Clinical candidate for one of the worst words in the drug industry: opioids
An all-outsourced model and a mere five employees
One of the first biotechs to go public via a SPAC (special purpose acquisition company)
The serendipitous discovery of an in-house material that works against COVID-19
Could Lynn Kirkpatrick have picked a more challenging biopharma to join as CEO?
“Our chemistry is just so compelling,” she says leaning into our Zoom call. “The opioid crisis needs a real solution.”
What brought my attention to Ensysce initially is a press release touting the importance of its growing relationship with a CDMO.
We’ll focus on that first, before subsequently working our way through all of which make Ensysce one of the most interesting of biopharma around today.
Motivation, And The Right CDMO
Ensysce was founded in 2008, and to add even another length of the yarn, originally focused on nanotube delivery of biologics.
It acquired a small molecule program in 2015, around which it has built two proprietary prodrug technologies: abuse resistant TAAP™ and overdose resistant MPAR™.
Kirkpatrick joined as CEO in 2009, and shifted to the small molecule program as it was beginning to produce two clinical candidates (PF614, a prodrug of oxycodone (currently phase 2), and PF329, an extended-release prodrug of hydromorphone (currently phase 1).
“These are small molecules inactivated through chemistry,” explains Kirkpatrick.
“Unless you swallow it, it doesn't release an opioid. And it performs in two steps, with the intermediate step designing all the pharmacokinetics.
You can have immediate or extended release based on that chemistry. Shelf live is solid as a rock, and cost of goods reasonable. It provides pain relief, but removes the chewing, injecting, and snorting capabilities. We also have a combination product that can prevent overdose.”
“Obviously, we're a company trying to raise and make money [much more on that in part two], but we also believe these products serve a societal need.
“Yes, these are opioids. Some people run when they hear that. But we have a CDMO partner with the right size and capability to take us from phase-one IND right through commercial.
“And everything – drug substance and product, all of our clinical activities – are outsourced.”
Selecting That Partner
Of course the CDMO selection criteria for Ensysce had to start with the ability to handle controlled substances. Kirkpatrick says there were in fact a significant number of options.
Next was the criteria for a single service-provider able to move the program from development to commercial, with all necessary support services.
Size was also top of mind. “The size of the CDMO was important, and we wanted it relative to our size,” explains Kirkpatrick.
“That was the best fit,” she says.
So good, Ensysce can manage this fully outsourced model essentially with one individual, Chief Operating Officer Jeffrey Millard.
Millard has experience in chemistry and pharmaceutical sciences covering all aspects of CMC. He’s led the R&D activities and the authoring of dozens of successful IND submissions. He has directed CMC efforts from discovery and in-licensing through commercial launch activities including the HER2 oncology product TUKYSA(r) (tucatinib) tablets.
To find that perfect fit, Kirkpatrick and Millard and team attended “a major industry meeting,” explains Kirkpatrick, inadvertently bolstering the thought we need to get back to in-person events sooner than later.
They interviewed about half a dozen CDMOs.
“I defer to the person with the expertise,” Kirkpatrick says. “But we all felt this CDMO among others understood us, had the full set of capabilities and capacity right now.”
Trust was next on the list of criteria for CDMO selection. That took some time.
Ensysce initially contracted for some limited work, which “worked out well.”
“We tested the waters, and still left other options open for ourselves,” Kirkpatrick explains. “We then decided to go to the next stage of actually having them manufacture clinical trial material.”
Altogether, the relationship building progressed via three, separate contracts. The first was that limited R&D, the next the development of drug product.
“We had the third in place, and obviously just executed on that recently” she says of the announcement for early-stage development and manufacturing services.
“We’ll evaluate again, but I believe there's no reason not to move to commercial together.”
I ask Kirkpatrick if she sat down with her counterpart at the CDMO, and more about that initial vetting process.
“Jeff Millard and I went and interviewed everybody involved there. Then we went again, particularly meeting with their chief scientific officer, to really get a comfort level.
“These site visits were pre-COVID; we have met the team and continue to have conversations, at that level.”
Fast forward, and today the two sides meet via biweekly calls.
“Their team is our team. That’s how it feels,” she says.
“We've got their project manager, quality, regulatory and analytic there – everybody working with us.
“And right up through commercial, it’s at the same location, which is beautiful.”
Beautiful in great part because:
“We have a team of only five executives,” says Kirkpatrick of the level of “virtual” Ensysce has maintained.
“I'm a chemist, so I can cross pollinate from chemistry, the pharmacology, IND, the clinical –We have CMC, a medical person, finance and business/commercial. We all wear many hats, though.
You Still Have To Manage
When asked to provide some advice for other CEOs in similar positions of outsourcing, Kirkpatrick doubles back to project management.
“This is a piece of advice one of my board members had given me” she says. “It doesn't matter if you have a project manager at the CDMO, you're always to some degree project-managing the project manager.
“In past experiences, I’ve found when relationships haven't worked well, the weak link has almost always been at the project management level. They are just not paying proper attention to your program, for whatever reason.
“So you can be virtual, but you do still have to be on top of everything.
More generally, she says biopharma executives should look for proven, broad expertise you don’t have, and see that it resides in state-of-the-art facilities.
“Thinking about the recent news of the issues with the CDMO producing two of the COVID-19 vaccines, even without knowing the details, it’s obvious they had lax quality control,” she says.
“And when you are outsourcing, as the sponsor you do not have control over the quality at the CDMO.
“So you really want to make sure the group you're working with has that quality aspect securely built in.”
In part two with Ensysce CEO Lynn Kirkpatrick, we’ll dive into the company’s becoming one of the first biopharma to go public via a special purpose acquisition company (SPAC). In part three, we’ll take a look at the serendipitous find of a potential small-molecule therapy for COVID-19.