Pfizer Inks Second Collaboration with Arvinas, Makes Billion-Dollar Investment on a Novel Agent for Breast Cancer Therapy

Targeted protein degraders are increasingly becoming the most sought-after modality in drug discovery. These small molecules enable the degradation of mutated proteins through the cell’s own disposal system instead of performing an inhibitory role.

A number of companies have pumped money into this rapidly evolving therapeutic area. A notable one is the 2018 collaboration of Arvinas, Inc. with Pfizer. In a deal worth up to $830 million, the duo signed a multi-year agreement to discover and develop drug candidates using Arvinas’ proprietary PROteolysis TArgeting Chimeras (PROTAC) technology. Building on that collaboration, now Arvinas has struck another billion-dollar deal with the pharma giant.

On July 22nd, the New Haven, Connecticut-based biotech announced a global collaboration with Pfizer to develop and commercialize its lead immuno-oncology candidate, ARV-471. Under the agreement, Arvinas will stand to gain $650 million in an upfront payment, in addition to a $350 million equity investment by Pfizer.

“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. CEO at Arvinas.

Endocrine Therapy for Breast Cancers

Approximately 80% of women diagnosed with breast cancer are triggered by estrogen receptor (ER) positive disease, with a 20% survival rate once metastasis occurs. Endocrine therapy, as monotherapy or in combination with standard of care, is one of the commonly used treatments for hormone receptor (HR) positive breast cancers. Yet, therapy options are still limited in a metastatic setting. Arvinas’ novel technology helps to tackle previously undruggable cancer targets.

“We share Pfizer’s deep commitment to people with breast cancer and are thrilled to partner with them to develop this potentially best-in-class therapy. Despite advancements in oncology in recent years, considerable unmet need persists in the treatment of HR+ breast cancer. Together with Pfizer, we will deploy our PROTAC technology in an effort to help people with this devastating disease,” Houston added.

ER Targeting Protein Degrader for Breast Cancer

Arvinas was launched in 2013 with a mission to develop drugs that treat diseases via the degradation of causative proteins. So far, the company has raised $111.6 million in three funding rounds. It focuses on two major therapeutic areas, oncology/immuno-oncology and neuroscience.

Its two lead candidates, ARV-110 and ARV-471, are protein degraders that emerged out of its PROTAC platform, targeting the androgen receptor and estrogen receptor, respectively. ARV-471 is intended for the potential treatment of patients with locally advanced or metastatic ER-positive / HER2 negative breast cancer.

ARV-471 registered positive interim data in a Phase 1 trial last December, recording a clinical benefit rate (CBR) of 42%. At the time, CMO Ron Peck remarked that ARV-471 is the most promising ER-targeting therapy in the clinic and showed better ER degradation than fulvestrant, the current treatment standard.

Studies Evaluating ARV-471

The drug is currently evaluated as a treatment for metastatic breast cancer in the following studies:

1. Phase 1 dose-escalation study,
2. Phase 1b combination study with Pfizer’s Ibrance, and 
3. Phase 2 monotherapy dose-expansion study (VERITAC)

Besides, both Arvinas and Pfizer are planning to initiate two additional trials in 2021, including a second Phase 1b combination trial with everolimus and another in the neoadjuvant setting.

In 2022, they are planning for Phase 3 studies across lines of therapy in metastatic breast cancer, including combinations with Ibrance, followed by pivotal studies in the early breast cancer setting.

“Building on Pfizer’s established leadership position in breast cancer science and CDK 4/6 inhibition, we are excited to work with Arvinas to maximize ARV-471, the first PROTAC for breast cancer with encouraging early clinical data and a potential novel hormonal therapy backbone for HR+ breast cancer,” said Jeff Settleman, Ph.D., CSO for Oncology Research and Development at Pfizer.

“This partnership complements Pfizer’s robust research activities in breast cancer, including our multiple next-generation CDK inhibitors currently in early clinical development.”

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Author

Rajaneesh K. Gopinath