Rigel Pharmaceuticals entered an exclusive global license agreement with Arvinas and Pfizer to commercialize Veppanu (vepdegestrant).

The deal marks a significant expansion of Rigel's oncology portfolio with the first FDA-approved Protac, a novel class of cancer therapy that degrades disease-causing proteins rather than simply inhibiting them.

What is Veppanu?

Veppanu is a Proteolysis Targeting Chimera, or Protac, a new class of heterobifunctional protein degraders that harness the body's natural cellular machinery to selectively eliminate disease-causing proteins rather than blocking their activity.¹ In breast cancer, the target is the estrogen receptor, which drives tumor growth in ER-positive disease and frequently develops mutations, particularly in the ESR1 gene, that confer resistance to standard endocrine therapies.

By degrading the mutant receptor entirely rather than inhibiting it, Veppanu is designed to overcome a key resistance mechanism that limits existing treatments.

Veppanu was approved by the FDA on May 1, 2026, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed after at least one line of endocrine therapy.¹

An FDA-authorized test is required to confirm ESR1 mutation status before treatment. On May 8, 2026, the National Comprehensive Cancer Network added vepdegestrant as a Category 2A treatment option for this patient population following at least one line of endocrine therapy plus a CDK 4/6 inhibitor.

What did the clinical trial show?

The approval is based on data from Veritac-2, a global, randomized, open-label Phase III trial presented at ASCO 2025 and simultaneously published in the New England Journal of Medicine.² Among patients with confirmed ESR1 mutations, vepdegestrant reduced the risk of disease progression or death by 43% compared to fulvestrant, with median progression-free survival of 5.0 months versus 2.1 months, a statistically significant and clinically meaningful improvement.² The majority of adverse events were low grade, with the most common including musculoskeletal pain, fatigue, nausea, and laboratory abnormalities.

"As many as 50% of patients emerge with an ESR1 mutation following exposure to endocrine therapy, developing resistance to standard treatments," said Erika Hamilton, M.D., chief development officer at Sarah Cannon Research Institute and Veritac-2 principal investigator. "Vepdegestrant provides a much-needed new treatment option for physicians that can fill a critical gap in care for patients with breast cancer."

What are the details of the agreement?

Rigel is set to pay Arvinas and Pfizer $70 million upfront along with an additional $15 million upon completion of certain development and manufacturing transition activities.¹ Rigel is also set to ontribute up to $40 million toward development activities over the next four years. Arvinas and Pfizer are entitled to tiered royalties on commercial sales ranging from mid-teens to mid-twenties percentages, plus up to $320 million in regulatory and commercial milestones.

Rigel holds exclusive global rights and the ability to sublicense outside the U.S. The agreement is expected to close in mid-June 2026, subject to antitrust clearance.¹

Raul Rodriguez, president and CEO of Rigel, said: "With its novel mechanism of action designed to address a key driver of resistance, Veppanu represents a compelling treatment option within this setting. We believe it has the potential to become a meaningful driver of long-term growth for Rigel."

Sources

1. Rigel Enters Exclusive Global Licensing Agreement for VEPPANU™ (vepdegestrant), an oral PROTAC, for the Treatment of 2L+ ER+/HER2-, ESR1m Advanced or Metastatic Breast Cancer Rigel Pharmaceuticals May 12, 2026 https://www.prnewswire.com/news-releases/rigel-enters-exclusive-global-licensing-agreement-for-veppanu-vepdegestrant-an-oral-protac-for-the-treatment-of-2l-erher2--esr1m-advanced-or-metastatic-breast-cancer-302769425.html
2. A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer (VERITAC-2) National Library of Medicine March 18, 2026 https://clinicaltrials.gov/study/NCT05654623