Sisunatovir, Oral Ph. II RSV Candidate, to Be Acquired by Pfizer

It’s always nice to see a small molecule making the front page of the news, especially when it’s a Molecule of the Month from last year! Pfizer and ReViral announced an agreement for Pfizer to acquire ReViral for up to $525 million, including milestones (amount upfront not disclosed). ReViral’s lead molecule sisunatovir, is an oral, lung-penetrant RSV virus fusion inhibitor dosed 50 mg BID.

sisunatovir chemical structure RSV candidate ReViral Pfizer acquisition

Sisunatovir demonstrated viral load reduction in a Ph. II healthy volunteer challenge study, and demonstrated safety and sufficient PK in the first part of a study in hospitalized infants. ReViral also has a Ph. I compound targeting the RSV N protein.

RSV can lead to severe respiratory infections in infants, immunocompromised individuals, and the elderly, and causes an estimated 160,000 deaths per year. Though vaccines and small molecules targeting RSV are in development, treatments for RSV are limited, with no commercial vaccine available yet (Pfizer has one in development, which recently received Breakthrough Therapy Designation). Sisunatovir received Fast Track designation from the FDA in 2020. Pfizer estimates the revenue for the acquired RSV programs may exceed $1.5B per year.

Sisunatovir’s discovery story was published by the ReViral team in 2021. The molecule is interesting because of some less common structural motifs including a potentially reactive spirocyclic cyclopropyl oxindole and a primary amine. Despite the potential for hERG inhibition, no QT effects were observed in the guinea pig model or dog telemetry studies, and the molecule was taken through human proof of concept. The paper describes the discovery and development thought process in detail and is a great drug discovery process case study from a smaller organization.

ReViral was co-founded by virologist Dr. Ken Powell and organic chemist Dr. Stuart Cockerill. Ken Powell was previously founder of Arrow Therapeutics acquired by AstraZeneca, a Professor at UCL, and an executive with the Wellcome Foundation before the Wellcome/Glaxo merger. Stuart Cockerill did his PhD at the University of Leeds and postdoc at Cornell before working at the Wellcome Foundation for 15 years. Stuart was an inventor of HER2 inhibitor lapatinib, and worked with Ken at Arrow Therapeutics as Head of Chemistry.

Though the acquisition price won’t set records, it is an interesting example of infectious disease activity outside of COVID in a commercial environment recently dominated by oncology and immunology.

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