Pfizer Strengthens Cancer Standing with Protein Degrader Collaboration

Pfizer_Erik McGregor/LightRocket via Getty

Erik McGregor/LightRocket via Getty Images

With 18 approved cancer medicines and biosimilars in its portfolio, Pfizer’s oncology arm continues to grow. This week the pharma giant announced a second collaboration agreement with Connecticut-based Arvinas to develop and commercialize its PROTAC estrogen receptor protein degrader.

Born from the Crews lab at Yale in 2001, the proteolysis-targeting chimera, PROTAC, technology hijacks the body’s natural cellular quality control mechanism to tag unwanted proteins for degradation. The company launched in 2013 from the research of Craig Crews to focus on primarily oncology indications in addition to inflammatory, autoimmune and rare diseases.

Pfizer is teaming up with Arvinas to tackle locally advanced or metastatic ER positive/HER2 negative breast cancer. The collaboration is a natural fit as Arvinas’ oral candidate, ARV-471, is in clinical trials as a monotherapy and in combination with Pfizer’s CDK 4/6 inhibitor IBRANCE®.

IBRANCE could use a boost to its efficacy profile. Although it’s Pfizer’s top-selling drug, it faced a double whammy of failed, multi-year adjuvant trials in 2020. PENELOPE-B flopped in the fall in patients with a high risk of cancer recurrence. Given alongside hormone therapy, the traditional treatment, for five years, IBRANCE couldn’t keep cancer from spreading any more than the hormone treatment did alone.

Earlier last year, the PALLAS trial was dropped after a futility analysis showed the broad group of patients with Stage 2 or 3 cancers actually fared worse than those on standard treatment.

By teaming up with Arvinas, IBRANCE has another chance to prove itself. With 80% of newly diagnosed cases of breast cancer ER+, ARV-471 has the potential for a huge impact.

In xenograft mouse models, Arvinas compared its candidate with the current standard of care, selective estrogen receptor degrader fulvestrant. The combination of ARV-471 with IBRANCE demonstrated superior rumor shrinkage to the combination of fulvestrant and IBRANCE.

“This collaboration has the potential to be transformational, as it combines our leadership in targeted protein degradation with Pfizer’s global capabilities and deep expertise in breast cancer. This should significantly enhance and accelerate the development and potential commercialization of ARV-471 while also advancing Arvinas’ strategy of building a global, integrated biopharmaceutical company,” said John Houston, Ph.D., chief executive officer at Arvinas. 

The deal gives Arvinas a nice infusion of cash as well. With an upfront payment of $650 million, the biopharma has a potential $1.4 billion in milestone payments. Profits and costs will be shared 50/50 between the two companies. Pfizer will also make a $350 million equity investment in Arvinas.

Pfizer’s first deal with Arvinas was worth up to $830 million, signed back in 2018.

Arvinas signed a new lease this month for a new HQ at a new state-of-the art life sciences facility in New Haven, its hometown. Right up the street from Yale, the company will lease three of the ten floors. Neighbors will include Yale and BioLabs.

The biotech’s massive pipeline includes nine oncology programs and four more in neuroscience. 

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