Arvinas Strikes Deals With Pfizer, Novartis to Compete in Protein Degrader Space


Pictured: Abstract collage of money, pills, prostate cancer cells and signing a contract/Taylor Tieden for BioSpace

When Arvinas agreed to license an oral targeted protein degrader for prostate cancer to Novartis last week, it represented a change in direction for the New Haven, Conn.–based biopharma firm.

In a 2021 deal with Pfizer worth up to $2.05 billion, Arvinas chose a partnership strategy to develop its oral estrogen receptor (ER) protein degrader for metastatic breast cancer, agreeing to split costs and profits evenly for the compound now known as vepdegestrant. Now, Novartis is handing over $150 million in aggregate upfront payments and pledging as much as $1.01 billion in milestones and royalties for complete manufacturing and commercialization rights both to Arvinas’ second-generation androgen receptor (AR) degrader ARV-766, which is currently in a Phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC), and a preclinical protein degrader also targeting mCRPC.

The decision was driven by the demands of vepdegestrant, which received FDA Fast Track designation in February as a Phase III trial proceeds, Arvinas President and CEO John Houston told BioSpace. “We give the [prostate cancer] program to Novartis. We get an upfront and we get milestones and royalties. That allows us to focus completely on vepdegestrant, our ER degrader.”

There are now dozens of biopharma companies, including giants like BMS, Novo Nordisk and Merck KgaA, involved in targeted protein degraders (TPD). Originally designed for cancers, TPD development has expanded into neurodegenerative diseases, rheumatoid arthritis and viral infections, including COVID-19. Research firm MarketDigits has estimated the global TPD market at $113.8 billion in 2022 and forecasts it to grow 10% annually to $247.5 billion by 2030.

One new development in this space is the oral TPD. So far, there have been no FDA approvals for orally bioavailable TPD therapies, but several companies beyond Arvinas are now pursuing this approach.

Arvinas was the first to begin dosing humans with an oral TPD, and Houston is confident the company’s strategic moves with Big Pharma will pay off. They have enabled the company to stay in a “solid financial situation” through the post-pandemic downturn in biotech investment, he said. The company had nearly $1.3 billion cash on hand at the end of 2023.

The Race to Be First

It’s a crowded space, with the sector attracting a lot of interest and investment of late as the first orally bioavailable therapeutic candidates approach the finish line. Salarius Pharmaceuticals is developing one for non-Hodgkins lymphoma, Kymera Therapeutics has a candidate for immune-moderated diseases and Amphista Therapeutics is testing one for neurodegenerative conditions.

According to research firm GlobalData, the amount of venture capital flowing into the TPD space as a whole grew by more than 2,000% in five years, to $707 million in 2022 from $33 million in 2017. Additional data provided to BioSpace by Alison Labya, business fundamentals analyst at GlobalData, showed that there were five such VC investments in the first quarter of 2024, collectively worth $277 million. That’s quite an uptick from Q1 2023 when three deals were struck for a total of just $17 million.

Moreover, partnership and licensing deals involving TPD drugs have rebounded from a 2021–23 slump as well, Labya said, highlighted by Arvinas’ deals with Novartis and Pfizer. In addition, VantAI inked a $674 million collaboration with Bristol Myers Squibb  in February, the same month Neomorph signed a nearly $1.5 billion TPD licensing agreement with Novo Nordisk. Both were for molecular glues, a type of TPD.

Arvinas’ two most advanced oral TPDs, ARV-766 and vepdegestrant, were developed on the company’s proprietary PROTAC (PROteolysis TArgeting Chimeras) platform, originally built by Arvinas founder Craig Crews, executive director of the Yale University Center for Molecular Discovery. “We showed right away that yes, the [R&D] team could design PROTACs . . . and we could specifically degrade an estrogen receptor and specifically degrade an androgen receptor,” Houston said. But it took nearly a decade to make the molecules orally bioavailable.

Arvinas’ Path Toward Market

Though Arvinas is out-licensing the entire ARV-766 program to Novartis, the handover will occur gradually over the rest of 2024. “We’ve got ongoing trials and we definitely don’t want to disrupt . . . those trials or the patients who are on the drugs,” Houston explained.

In the 50-50 vepdegestrant partnership with Pfizer, Arvinas will take the U.S. marketing lead, so the company will have to build its salesforce if the drug is approved. “That’s going to be a really significant growth driver for Arvinas,” Houston said. However, he cited the cost of doing the same thing with ARV-766 as the reason for licensing to Novartis, despite the company being in a “healthy” financial position, having recently raised $350 million in a private placement.

The company is undergoing some leadership turnover as it chases approval. Last month, Arvinas brought in a new chief medical officer, Noah Berkowitz, formerly head of the hematology development unit at BMS. Houston said the company was drawn to Berkowitz’s experience taking drug candidates from Phase III to launch. Meanwhile, Sean Cassidy, who had been CFO since 2014, departed Feb. 29, and the company is now searching for a permanent finance chief.

Arvinas expects progression-free survival data for ARV-766 by mid-2024 and is looking at a potential 2025 launch, "if all goes well in terms of our data,” Houston said.

Neil Versel is the business editor at BioSpace. You can reach him at Follow him on LinkedIn or X.

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