Arvinas and Quantum Leap Healthcare Announce Clinical Study to Evaluate Vepdegestrant (ARV-471) in I-SPY-2 Endocrine Optimization Platform (EOP) Clinical Trial

NEW HAVEN, Conn. and SAN FRANCISCO, May 2, 2023 /PRNewswire/ -- Arvinas, Inc. (Nasdaq: ARVN) and Quantum Leap Healthcare Collaborative™ today announced that Arvinas' vepdegestrant (ARV-471), a novel PROTAC® estrogen receptor (ER) protein degrader being co-developed with Pfizer Inc. will be evaluated in the ongoing I-SPY TRIAL endocrine program sponsored by Quantum Leap. This study targets patients with newly diagnosed ER positive invasive cancer. Vepdegestrant is in Phase 3 clinical development for the treatment of patients with locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

The I-SPY-2 Endocrine Optimization Platform (EOP) study (NCT01042379) will include a vepdegestrant monotherapy arm and a vepdegestrant in combination with letrozole arm. This study is focused on patients with clinically high-risk (stage 2/3) ER+/HER2- breast cancer, but molecularly low risk (MammaPrint low risk signature), a subset of patients with substantial risk for late recurrence.

Quantum Leap opened the EOP program in 2021 to specifically assess treatment options for this subset of patients, and work to find an early endpoint to measure the success of therapy. EOP is a sub-study within the main I-SPY-2 clinical trial utilizing neoadjuvant endocrine therapy in patients whose tumors are predicted to be sensitive to endocrine therapy but for whom chemotherapy is expected to provide little or no benefit.

"I-SPY TRIALs focus on high-impact experimental treatments that may benefit patients, providers, and researchers, and Arvinas is thrilled to be part of this innovative I-SPY-2 clinical trial," said John Houston, Ph.D., president and chief executive officer at Arvinas. "There is an unmet medical need for novel agents in life-threatening diseases and this research is vital to advancing patient outcomes. In all of our investigational research, our commitment is to patient safety and care, and we are excited by vepdegestrant's potential to become a new standard of care for patients with ER+/HER2- breast cancer."

"The heart of the I-SPY TRIALs is to change how new breast cancer treatments are developed, to find treatments that are more personalized, effective, and less toxic, faster. We are excited to be partnering with Arvinas and investigating the potential positive benefits of vepdegestrant. Women need better and more tolerable options for extended endocrine therapy. We hope this will be one of them." said Dr. Laura Esserman, co-principal investigator of the I-SPY TRIAL and founder of Quantum Leap.

Arvinas will provide vepdegestrant and financial support to Quantum Leap for this investigational study. Quantum Leap is the sponsor of the I-SPY program, which includes 41 open sites. All I-SPY sites have the EOP program open.

About vepdegestrant (ARV-471)
Vepdegestrant is an investigational, orally-bioavailable PROTAC® protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with early and locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Use of vepdegestrant in the ongoing and planned clinical trials will continue to monitor and evaluate patient safety and anti-tumor activity.

In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About Arvinas
Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC® Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC® targeted protein degraders, that are designed to harness the body's own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. In addition to its robust preclinical pipeline of PROTAC® protein degraders against validated and "undruggable" targets, the company has three investigational clinical-stage programs: bavdegalutamide (ARV-110) and ARV-766 for the treatment of men with metastatic castration-resistant prostate cancer; and vepdegestrant (ARV-471) for the treatment of patients with early and locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. For more information, visit www.arvinas.com.

About Quantum Leap Healthcare Collaborative
Quantum Leap Healthcare Collaborative is a 501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our Quantum Leap's mission is to integrate care and research, and to foster high-impact trials with embedded clinical processes and systems technology and improved data management, greater access to clinical trial matching, and greater benefit to patients, providers, and researchers. Quantum Leap's goal is to improve and save lives. Quantum Leap provides operational, financial, and regulatory oversight to I-SPY. For more information, visit https://www.quantumleaphealth.org/.

About the I-SPY TRIALs
The I-SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) (I-SPY 2 TRIAL) was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The Endocrine Optimization Pilot (EOP) is developing better endpoints and new endocrine targeted agents for stage 2/3 molecularly low risk breast cancer. The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 30 major U.S. cancer research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential of the I-SPY endocrine program, the potential for vepdegestrant (ARV-471) to become the standard of care for patients with ER+/HER2- breast cancer, and the potential and therapeutic benefits of our clinical programs, vepdegestrant (ARV-471), bavdegalutamide (ARV-110), and ARV-766. The terms "expect," "potential," "will," "intend," "believe," and "plan," derivatives of these words, and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to, risks associated with the successful conduct and completion of clinical trials and development for Arvinas' investigational clinical candidates, including vepdegestrant (ARV-471). Other risks and uncertainties include those identified under the heading "Risk Factors" in Arvinas' Annual Report on Form 10-K for the year ended December 31, 2022, and other filings that Arvinas may make with the U.S. Securities and Exchange Commission in the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and, except as required by law, Arvinas does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.

SOURCE Quantum Leap Healthcare Collaborative