Pfizer's search for Paxlovid's COVID-busting sibling leads to low-profile antiviral biotech

Pfizer’s COVID-19 drug Paxlovid has rapidly grown into a $22 billion-a-year mega blockbuster. Now, the Big Pharma wants to develop a sibling to the antiviral—and has identified Clear Creek Bio as an ally that can help make it happen.

The antiviral component of Paxlovid, nirmatrelvir, is an oral protease inhibitor that targets SARS-CoV-2’s main protease (Mpro). The protease is critical to the cleavage of polypeptides that takes place during the replication of SARS-CoV-2, leading researchers to identify it as the Achilles heel of the virus, but it isn’t the only enzyme involved in the process. 

Papain-like protease (PLpro) is SARS-CoV-2’s other essential cysteine enzyme. Like the main protease, PLpro is critical to viral replication and assembly, making it an attractive target for researchers that want to throw a wrench in the works of SARS-CoV-2’s machinery.

The problem is PLpro lacks obvious binding pockets and, as such, potent inhibitors of the protease are hard to find. Led by Vikram Sheel Kumar, M.D., Clear Creek Bio applied its antiviral discovery capabilities to the challenge, emerging with potent inhibitors of the protease. The National Institutes of Health inked an agreement to support the program up to the completion of IND-enabling studies.

Now, the work has caught the attention of Pfizer. Charlotte Allerton, chief scientific officer, anti-infectives and head of medicine design at Pfizer, explained the thinking behind the deal with Clear Creek Bio in a statement. 

“It is critical that we try to stay ahead of the virus, continuing to advance clinical development opportunities for our current oral therapy as well as innovating through our internal programs and strategic partnerships to bring forward additional monotherapy and/or combination treatment candidates that we believe may play a role in the ongoing fight against COVID-19,” Allerton said.

Pfizer will work with Clear Creek Bio to identify a PLpro candidate to move into the clinic. Once human studies get underway, Pfizer will take full responsibility for development and commercialization, paying Clear Creek Bio milestones on top of the undisclosed upfront payment it made to seal the deal.