Oncology Biotech CEO Activates “Latent Viral Side” Against COVID-19

Opinion

Xconomy San Diego — 

In every National Football League game, athletes must accomplish two difficult things that rest at opposite ends of the spectrum: rigor and speed. If their movements are off by even half a second, they risk being tackled by their opponent. Game over.

In this COVID-19 day and age, believe it or not, the NFL serves as a valuable model for the life science industry. If we are to succeed at rapid development of effective treatments, scientists and clinicians are forced to think as rigorously as they ever have—just at warp speed. Sounds simple, right? Just ask the guy who was tackled by the linebacker.

With two decades of experience in antiviral drug development and as CEO of a company focused on correcting cellular processes that go haywire in disease, I started to look into coronaviruses back in January, when the first COVID-19 cases became known to the outside world. Sure enough, I found that SARS-CoV-2 is an RNA virus. This meant that inhibiting RNA translation into proteins (which is central to my company’s approach) could potentially have antiviral activity. But even though my company eFFECTOR Therapeutics had two selective translation regulator inhibitors in clinical development in cancer, I didn’t think too much about it. It felt like a distracting science project at the time. It hadn’t hit me how critical the disease truly was.

As the number of cases rose exponentially and reports of the devastation of COVID-19 were published, I started to understand this was a big deal. A massive deal. I had a responsibility as a scientist to do what I could in treating this disease, ignoring pestering thoughts about my potential delusions of grandeur or hero complex. I also had to put aside the notion that “puny, little me” couldn’t do anything about this global pandemic, that the World Health Organization would take care of it. From an objective scientific perspective, there was a very real chance that zotatifin—one of eFFECTOR’s product candidates that targets eukaryotic initiation factor 4A (eIF4A)—could have activity against SARS-CoV-2. Because of this, I submitted it for testing in an independent research study led by Nevan Krogan at the University of California, San Francisco.

Once submitted, I felt that I’d done my social responsibility, thinking that there would be more effective compounds in the study. But four weeks later, I found out that zotatifin had confirmed in vitro antiviral activity against SARS-CoV-2 and was one of the most active agents identified in the study, which just published in Nature. This was a startling moment for the CEO of a small biotech focused on cancer drug development.

While I was initially caught unprepared at the outcome of the study, scientifically speaking, I wasn’t surprised as eIF4A is a critical component in translation initiation. It’s a fundamental capability of all cells, which cancer redirects for its own growth and proliferation. Viruses are no different in this case. They hijack the same cellular machinery for replication.

Regardless of my initial apprehension about the impact it would have on my company if we were to pursue development of our product candidate for COVID-19, I said to myself, “we have to do this.” The scientific justification and the potential for human health were just too high.

In a way, you could say that my latent viral side has become reactivated. I contacted drug development and scientist contacts I had worked with in the past in the antiviral space, and we’re quickly coming up with a plan to test zotatifin’s activity against COVID-19 in clinical settings.

When I think about other infectious diseases that have swept the globe in the modern era, we’re living in an unprecedented time. Our understanding of HIV, for example, evolved over the course of two to five years. SARS and MERS came and went fairly quickly. It’s extraordinarily rare to have to conduct clinical and operational planning when the information we rely upon to do these things only came out yesterday—or even tomorrow. The life science community is forced to adopt incredible resiliency, discipline and rigor, all at the same time, to respond to something completely outside of the norm.

And the life science community is answering. I have never seen such remarkable collaboration. In a mere two to three months, we’ve gone from recognition of the problem to outcomes of randomized clinical trials, an unheard-of feat in drug development. This has only been made possible by our network amplifying itself and the partnerships that are happening all across the board.

I feel confident when I say that our industry is accomplishing what those same NFL athletes are: rigor and speed. We are conducting clinical courses and lab experiments at a pace I’ve never seen before. I don’t think this lesson will be lost on anyone, and winners of innovation over the next 10 to 20 years will take these collaborative learnings to heart as we enter a new era in drug development.