Pfizer and Clear Creek Bio, a private biotechnology company, today announced a research partnership and an exclusive license agreement to advance the discovery and development of potential oral antivirals for the treatment of COVID-19. The focus of the partnership will be on possible inhibitors of the SARS-CoV-2 papain-like protease (PLpro), which similar to the main protease (Mpro), is needed for viral replication. If successful, this program will add direct-acting antiviral agents against a new SARS-CoV-2 target to Pfizer’s existing portfolio of COVID-19 products, enhancing the company’s cutting-edge anti-infective pipeline.
The Pursuit of PLpro
“We held an internal meeting in April 2021 with medicinal chemistry, virology, and antiviral drug developers who had progressed drugs to products, and when we looked across the SARS-CoV-2 druggable genome, PLpro was staring at us as an essential viral protease that hadn’t received the recognition it deserved,” Vikram Sheel Kumar, MD, CEO of Clear Creek Bio, told GEN Edge.
“We looked at that target and said we could initiate a substantial chemistry effort against this target. We went from idea to deal in about 20 months in the pandemic, where we still think we can have an impact.”
SARS-CoV-2 has two essential proteases. When the virus is replicating, it first expresses multiple proteins tethered together in a polyprotein. It depends on its proteases to cleave those proteins into functional forms that then play their roles in various parts of the viral life cycle.
The research collaboration and license that Clear Creek Bio and Pfizer signed give Clear Creek Bio a chance to work together on lead optimization and hand over a potential development candidate to Pfizer so that it can be tested in the clinic. It also gives Clear Creek Bio money up front and royalties and milestone payments, the details of which were not made public.
Kumar said, “We have been able to make progress with an amazing team on what I consider quite a quick timeline with just extreme focus, and now we’ve been able to partner with Pfizer.”
Looking Beyond COVID
In addition to the PLpro program, Clear Creek Bio is evaluating Brequinar, a potent oral inhibitor of dihydroorotate dehydrogenase (DHODH), in combination with other therapeutics against a wide range of RNA viruses.
“It’s been exciting to start by acquiring an asset from pharma—we acquired Brequinar from Bristol Myers—to then do our in-house discovery program on PLpro inhibitors and out-license that to Pfizer,” said Kumar. “We’re in this unique partnering ecosystem where you can play your role as a small company and ultimately add value to patients. It’s been really exciting to be able to take the risks that have been required to advance the science of antivirals for COVID.”