With Lilly on board, Entos’ medical chief champions genetic platform with ‘unlimited’ potential

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Entos Pharmaceuticals is on the verge of “leveling up,” and Steve Chen is excited to help them get there.

“I think the company right now is actually going through what I would call a major inflection point,” says Chen, who joined clinical-stage Entos earlier this year as chief medical officer on the heels of a new research and collaboration agreement between Entos and Eli Lilly & Co.

Under the agreement, Lilly is acquiring exclusive rights to Entos’ Fusogenex nucleic acid delivery technology to research, develop and commercialize nucleic acid products targeting the central and peripheral nervous system. As part of the deal, Entos scored a $50 million up front payment, including an equity investment in Eli Lilly, and could receive up to $400 million more in development and commercial milestone payments.

It’s a technology called a proteolipid vehicle, or PLV, that delivers nucleic acid therapies — which target diseases at the genetic level — without the toxicity that usually accompanies that delivery.

Entos is working to turn that delivery platform into drug indications for patients, and one of the ways it’s doing so is through partnerships like the one with Eli Lilly.

“The company is poised right now to actually start translating this research information and converting it into the development piece,” Chen says.

Getting drugs into patients’ hands

The excitement of actually getting drugs into patients’ hands has been a throughline of Chen’s career. A self-described “recovering academic and accidental drug developer,” Chen joined the pharma industry in 2008 via academic medicine after leading the clinical research unit at the Center for Human Nutrition at UCLA and serving as a staff physician for emergency medicine at West Los Angeles Veteran Affairs Hospital.

While at UCLA, he focused on type 2 diabetes and obesity and ran all the clinical trials for his own department. He made the leap to industry with Amylin Pharmaceuticals after marveling at how drug companies could translate academic discoveries into real solutions for patients.

“I’ll be very honest and sincere about this … the diseases that we’re treating today when I was in medical school? I would say that’s science fiction.”

Steve Chen

Entos Pharmaceuticals Chief Medical Officer

He initially gave himself two years to decide whether working in the pharma industry was for him — he could always go back to clinical medicine, he reasoned — but found that he enjoyed the work, and the payoff.

“In academic medicine … I have friends who are still studying the same receptor that they studied in grad school,” he says. “And don’t get me wrong, I think we need that to drive science. But for me as a clinician it’s also, with all this great science that we’re developing, how do we translate that into helping actual patients?”

Of course, Chen stuck with the industry longer than two years — even though he had to answer his father’s “very traditional Asian thinking” that his son “went to medical school… why are you not seeing patients?” — and is still energized by the prospect of helping so many people.

“I just kind of did a back-of-the-napkin calculation that if I stay in clinical medicine, how many patients at the end of day, in my whole career, could I really have helped, versus if I could actually successfully develop a drug?” he says. “And of all the drugs that I’ve worked on … we’re talking about [a] couple million patients, which you’re not going to be able to do in the clinical practice setting. And so, from that perspective, it’s extremely rewarding.”

In addition to Amylin Pharmaceuticals, Chen has held leadership positions at Cellics Therapeutics, La Jolla Pharmaceutical Company, Takeda and Eli Lilly. That’s not to say his pharma career has been all smooth sailing: He remembers that within four months of joining Amylin, the company laid off 25% of the workforce.

“To me, that was kind of like a wake-up call: welcome to industry,” he says. But it didn’t matter: He was hooked and still values ​​getting to work in a wide variety of drug development processes in his years with Amylin.

The low-hanging fruit and beyond

Chen continues to be amazed by drug discovery and the way it’s evolved over the past 20 years into biologics and now, genetic medicine.

“I’ll be very honest and sincere about this … the diseases that we’re treating today when I was in medical school? I would say that’s science fiction,” he says.

That’s one of the things that drew him to Entos.

“We now have the tools to treat a lot of diseases, but the problem that we’re facing with it is, how do we deliver that?” he says.

Although he admits to being “biased,” Chen believes the Fusogenex PLV platform provides “the best of both worlds” by delivering the nucleic acid therapy “cargo” directly into cells while leveraging neutral lipids to avoid the toxicity that comes with other delivery platforms like cationic or ionizable lipid nanoparticle platforms.

“I think the PLV platform is in a good position to actually transform how we deliver a lot of these genetic payloads,” he says. “I think it can open up brand new areas where, I would say, even five years ago, we were thinking that we can’t treat those diseases. Now we can.”

The clinical areas that Entos are targeting with the platform include oncology, age-related diseases, genetic diseases and neurological disorders. The company also has two COVID-19 DNA vaccines in development, including one that’s in phase 2 clinical trials in South Africa.

Several of those drugs are in development with partners like OncoSenX, Aegis Life and BioMarin. Now the new Lilly deal serves several functions for the company, Chen says.

“One is that with the influx of resources, it allows Entos to go much faster than it has before,” he says. “And two, obviously, is also a kind of external validation of the platform.”

Although Entos is still working on commercializing these products, Chen believes they’re only scratching the surface of what this kind of technology can do, calling the genetic diseases the platform’s “low-hanging fruit.” The company says that the health indications that could be addressed with the Fusogenex PLV platform is “unlimited,” and Chen imagines that they can also start thinking about solving genetic targeting for chronic diseases and more.

Of course, that’s pretty typical for Chen.

“I actually like to think a little bit bigger,” he says.

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