Neither Arvinas nor Pfizer now wants vepdegestrant

For some time it’s looked like Pfizer might walk away from its Arvinas-partnered oestrogen degrader vepdegestrant, but the companies have now proffered an unusual solution: they will jointly seek a new partner for the project.

On the face of it the decision seems pragmatic, but it raises the question: who might want to license vepdegestrant? The degrader looks likely to be third to market, following Menarini's approved drug Orserdu and Lilly’s imlunestrant, which is awaiting an FDA decision. And, despite Arvinas’s claims of differentiation, vepdegestrant hasn’t shown a benefit outside ESR1-mutant ER-positive, HER2-negative breast cancer, making it look just like the other oestrogen degraders.

Who will buy?

In theory at least vepdegestrant could tempt the likes of Roivant, which has made a business out of licensing in unloved assets and building businesses around them. Companies with a similar model include PureTech Health and Biohaven; the latter is pursuing a “fast follower” strategy in oncology, and already has several degraders in its pipeline, albeit in inflammatory disorders.

However, for these groups or any others, any deal would turn on the price that Arvinas and Pfizer are demanding for vepdegestrant, especially in light of the project's lateness to market and lack of differentiation.

Sales in second-line breast cancer, where vepdegestrant is awaiting an FDA decision by 5 June 2026, will be limited to $500m or less, estimates Evercore ISI’s Jonathan Miller. The “real potential”, he reckons, is in first-line disease as part of a combination therapy, but this would require a large phase 3, perhaps limiting possible buyers to bigger players with deeper pockets.

Miller speculated that companies with existing CDK or PI3K inhibitor franchises could be bidders. The obvious option here is Novartis, which markets Kisqali and Piqray, but that group already has a relationship with another oestrogen degrader player, Olema, even if it’s shown no signs so far of making a long-rumoured acquisition.

Meanwhile, Lilly, which sells the CDK4/6 inhibitor Verzenio, already has a SERD in the aforementioned imlunestrant. And Roche, which markets the PI3Kα blocker Itovebi, is developing its own SERD, giredestrant. AstraZeneca, with camizestrant, can also be ruled out of the running.

Cutting costs

As for Arvinas, it’s cutting costs, revealing plans to cull another 15% of its workforce, largely in commercial vepdegestrant roles. Together with a 30% reduction in jobs announced in May, the group hopes to save around $100m per year versus 2024. Arvinas reiterated previous cash runway guidance, saying it’s funded into the second half of 2028.

The company will now focus on its early-stage pipeline, namely the BCL6 degrader ARV-393, and the KRAS G12D degrader ARV-806 (as well as a neurodegenerative disease project).

The lead KRAS G12D degrader player is Astellas, although that company’s most advanced project, ASP3082, produced disappointing data at ESMO last year. Astellas has a back-up asset, ASP4396, while the other clinical-stage contender, according to OncologyPipeline, is Ranok Therapeutics’ RNK08954.

Other clinical-stage BCL6 degrader players are Bristol Myers Squibb, whose BMS-986458 has produced an ORR of 81% among 17 relapsed lymphoma patients, and Haisco, with HSK47977.

Arvinas’s stock climbed 5% on Thursday morning, suggesting that investors already saw little value in vepdegestrant. Now the company needs to find a partner that sees potential where Arvinas, Pfizer, and apparently Wall Street, do not.

Beyond vepdeg: Arvinas’s other clinical-stage cancer degraders

Source: OncologyPipeline.