Arvinas Inc. and Bayer AG will leverage Arvinas' PROTAC (PROteolysis TArgeting Chimeras) protein degrader platform to develop therapeutics for patients with cardiovascular, oncological and gynecological diseases.

The deal involves more than $110 million in up-front cash, committed funding and equity investment in Arvinas from Bayer. Timelines and milestones are yet to be set, John Houston, Arvinas president and CEO, told BioWorld.

"We hope to say five or six years where we have one or two assets for commercialization," he said.

That's a normal timeline for pharma R&D, he said, adding that Arvinas will go through Bayer's clinical candidate criteria to determine milestones. The targets will be selected by Bayer, which is allowed to make substitutions for any initial target candidates, subject to conditions and based on the stage of research for the target. Bayer will make research funding payments of $3 million per year in each of the first four research program years.

"Each will have uniquely different timelines," Houston said. "As the assets progress, we'll announce the timelines."

Under the terms of the collaboration agreement, New Haven, Conn.-based Arvinas will receive an aggregate up-front payment of $17.5 million within 30 days and is entitled to receive up to an additional $12 million in research funding payments, subject to increases. Arvinas is also eligible to receive up to $197.5 million in development milestones and up to $490 million in sales-based milestones for all designated targets. In addition, Arvinas is eligible to receive, on net sales of PROTAC targeted protein degrader-related products, mid-single-digit to low double-digit tiered royalties, which may be subject to reductions. Bayer will own the rights to lead structures generated in the collaboration.

The agreement was good news for Arvinas stock (NASDAQ:ARVN), which closed Tuesday's trading up 9.68% for the day and up 37% since its Nasdaq debut on Sept. 27.

Arvinas, Bayer and Bayer Cropscience LP are also jointly launching a company to use PROTAC for developing agricultural applications. Houston said he believes the collaboration is the first to apply the platform to agriculture. The deal is designed to leverage Arvinas' expertise in targeted protein degradation, a field at the core of the company since its founding in 2013, and Bayer's decades of experience in developing both human therapies and agricultural technologies. The goal is to address resistance mechanisms in plants to existing agricultural solutions to control weeds, insects and disease.

"It's a unique deal for us and for Bayer, combining crop sciences and biosciences, which is unusual," Houston said.

The agreement with Bayer does not alter the timelines and milestones for Arvinas' current pipeline, which Houston labeled as "progressing and fully funded."

Arvinas said its cash and investments will fund operations into 2021.

In its own pipeline, Arvinas has ARV-100, for which the FDA granted fast track designation in May. ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor protein.

On March 25, Arvinas initiated patient dosing in its phase I trial of ARV-110. The study is evaluating the safety, tolerability and pharmacokinetics in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on standard-of-care therapies. Arvinas said it believes ARV-110 is the first in a new class of targeted protein degraders to enter human clinical trials and anticipates preliminary data from the study in the second half of 2019. The trial is expected to enroll approximately 28 to 36 patients with progressive mCRPC and will evaluate the biochemical and clinical activity of ARV-110 by assessing prostate-specific antigen levels, androgen receptor degradation, radiographic measurements of evaluable lesions, and other exploratory markers of disease burden. The study began March 1 and is expected to be completed Dec. 31, 2021.

The first collaboration for Arvinas, a Yale University spin-off, was with Merck & Co. Inc. in 2015, with the goal of creating therapies for multiple diseases, including cancer. The pact included an undisclosed up-front payment, funding to support Merck-related research, and up to $434 million in milestone payments. (See BioWorld Today, April 8, 2015.)

In late 2017, Arvinas expanded a 2015 PROTAC license agreement with Genentech, a unit of Basel, Switzerland-based Roche Holding AG, adding disease targets and making Arvinas eligible for development and commercialization milestone payments in excess of $650 million, plus tiered sales royalties. In 2015, Arvinas landed a potential $830 million multiyear research collaboration and license agreement with Pfizer Inc., of New York, to develop candidates using the PROTAC approach. (See BioWorld, Jan. 4, 2018.)