Rigel Pharmaceuticals, Inc. (NASDAQ:RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced that it has entered into an exclusive, global license agreement with Arvinas, Inc. (Arvinas) and Pfizer Inc. (Pfizer), subject to regulatory clearance, to develop, manufacture and commercialize VEPPANU™ (vepdegestrant), the first and only U.S. Food and Drug Administration (FDA)-approved oral PROteolysis TArgeting Chimera (PROTAC). PROTACs are part of a new class of heterobifunctional protein degraders designed to harness the body's natural machinery to selectively degrade, rather than inhibit, disease-causing proteins. In the Phase 3 VERITAC-2 clinical trial, which evaluated vepdegestrant in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer (mBC), vepdegestrant was generally well tolerated and demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as compared to fulvestrant.

"Our transformational growth strategy took a significant step forward today as we plan to enter a targeted segment of the sizable breast cancer market, focused on patients with limited treatment options following progression on endocrine therapy. With its novel mechanism of action designed to address a key driver of resistance, VEPPANU represents a compelling treatment option within this setting," said Raul Rodriguez, Rigel's president and CEO. "Importantly, we are well positioned to advance this important new treatment, supported by a highly experienced commercial and medical affairs organization and a proven track record of successfully launching newly-acquired assets. VEPPANU is expected to contribute strong revenue growth in our expanding commercial portfolio, and we believe it has the potential to become a meaningful driver of long-term growth for Rigel."

On May 31, 2025, pivotal results for VERITAC-2 (NCT05654623), a global, randomized, open-label Phase 3 clinical trial were presented in an oral presentation of a late-breaking abstract at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, and simultaneously published in the New England Journal of Medicine. On August 8, 2025, the FDA accepted the New Drug Application (NDA) for vepdegestrant (ARV-471) to treat ER+/HER2-, ESR1-mutated advanced breast cancer and set a Prescription Drug User Fee Act (PDUFA) action date of June 5, 2026.

On May 1, 2026, VEPPANU (vepdegestrant) was approved by the FDA for the treatment of adults with ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. FDA approval was granted based on data from VERITAC-2 clinical trial that evaluated vepdegestrant versus fulvestrant in patients with ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer. In the trial, among patients with an ESR1 mutation (n=270), vepdegestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 43% compared to fulvestrant. Median PFS was 5.0 months (95% CI: 3.7, 7.4) in the vepdegestrant arm and 2.1 months (95% CI: 1.9, 3.5) in the fulvestrant arm (hazard ratio 0.57 [95% CI: 0.42, 0.77]; p-value 0.0001). Overall survival was immature with 16% of deaths in this population at the time of the PFS analysis. The majority of adverse events with vepdegestrant were low grade (Grade 1-2) and the most common (≥10%) adverse reactions, including laboratory abnormalities, were decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, and constipation.

"The ER+/HER2- patient population is the most prevalent breast cancer subtype, where treatment with endocrine therapies is the current standard of care. 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, Late Phase and Director, Breast Cancer Research at Sarah Cannon Research Institute, and Phase 3 VERITAC-2 principal investigator. "As a PROTAC, vepdegestrant is mechanistically differentiated and has a demonstrated efficacy and a safety profile observed in clinical trials. Vepdegestrant provides a much-needed new treatment option for physicians that can fill a critical gap in care for patients with breast cancer."

On May 8, 2026, the National Comprehensive Cancer Network® (NCCN®) added vepdegestrant to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer. Vepdegestrant was added as a Category 2A treatment option for patients with hormone receptor (HR)-positive/HER2-negative, ESR1-mutated advanced or metastatic breast cancer after at least one line of endocrine therapy + cyclin-dependent kinase (CDK) 4/6 inhibitor.*

Transaction Details

Under the terms of the agreement, Rigel will be granted exclusive global rights to develop, manufacture and commercialize VEPPANU. Arvinas and Pfizer will receive an upfront payment of $70.0 million and an additional $15.0 million upon successful completion of certain development and manufacturing transition activities, to be distributed to Arvinas and Pfizer.

Pfizer and Arvinas will continue to be responsible for current ongoing development activities and Rigel will contribute up to $40.0 million towards certain development activities over the next four years.

Arvinas and Pfizer are entitled to receive tiered royalties on commercial sales of VEPPANU ranging from mid-teens to mid-twenties. Arvinas and Pfizer are also eligible to receive a total of up to an additional $320.0 million in connection with the achievement of certain regulatory and commercial milestones.

Rigel will be responsible for the launch and commercialization of VEPPANU in the U.S. and has global rights with the ability to sublicense to potential partners to further develop and commercialize vepdegestrant outside the U.S. Arvinas and Pfizer will be entitled to a percentage of sublicensing revenue generated outside the U.S.

The effectiveness of the agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to close in mid-June 2026.