On May 7, 2023 Arvinas, Inc., a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the first quarter ended March 31, 2024 and provided a corporate update (Press release, Arvinas, MAY 7, 2024, View Source [SID1234642757]).

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"Our recently announced agreement with Novartis creates significant value for Arvinas and further validates our innovative PROTAC protein degrader platform and its potential to deliver important new treatment options for patients," said John Houston, Ph.D., Chairperson, President and Chief Executive Officer at Arvinas. "In addition to this strategic transaction, and together with Pfizer, we continued making meaningful progress advancing our Phase 3 clinical programs with vepdegestrant in ER+/HER2- metastatic breast cancer. During the quarter we also advanced ARV-102, our first PROTAC degrader with the potential to treat neurodegenerative diseases, into a Phase 1 clinical trial and we remain on track to initiate a first-in-human Phase 1 clinical trial with ARV-393, our BCL6 targeting PROTAC degrader, by the end of the second quarter. We also further strengthened our management team with key hires as we approach our first Phase 3 readout and continue progressing multiple ongoing and planned clinical-stage programs."

Recent Developments and First Quarter Business Highlights
Strategic Transaction with Novartis
•Announced an exclusive strategic license agreement with Novartis (NYSE: NVS) for the worldwide development and commercialization of ARV-766, Arvinas’ second generation PROTAC androgen receptor (AR) degrader for patients with prostate cancer, and the sale of Arvinas’ preclinical AR-V7 program.
◦Upon closing, Arvinas will receive a $150 million upfront payment for the license of ARV-766 and the sale of Arvinas’ preclinical AR-V7 program, with the potential under the License Agreement for up to $1.01 billion in development, regulatory, and commercial milestones, as well as tiered royalties.

Vepdegestrant
•Completed enrollment of the study lead-in for the VERITAC-3 Phase 3 clinical trial of vepdegestrant and palbociclib as a first-line treatment in patients with estrogen receptor (ER) positive/human growth epidermal growth factor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer.
•Received U.S. Food and Drug Administration Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
•Initiated dosing in a Phase 1b/2 clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (PF-07220060) (TACTIVE-K: ClinicalTrials.gov Identifier: NCT06206837).
•Initiated dosing in an additional arm of the Phase 1b/2 combination umbrella trial with the CDK7 inhibitor samuraciclib (TACTIVE-U: ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).

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•Announced the inclusion of an additional arm in the I-SPY-2 Endocrine Optimization Platform (EOP) study (NCT01042379) that will evaluate vepdegestrant in combination with abemaciclib.
◦Vepdegestrant is also being evaluated in a monotherapy arm and in combination with letrozole arm in the ongoing I-SPY TRIAL endocrine optimization program sponsored by Quantum Leap.

Pipeline
•Initiated dosing in a first-in-human Phase 1 clinical trial in healthy volunteers with ARV-102, the Company’s first neuroscience PROTAC degrader targeting leucine-rich repeat kinase 2(LRRK2) as a potential treatment for idiopathic Parkinson’s disease and progressive supranuclear palsy.

Corporate
•Announced the appointment of Noah Berkowitz, M.D, Ph.D., to the role of Chief Medical Officer.
•Announced the appointment of Jared Freedberg, J.D., as General Counsel.
•Announced the resignation of Chief Financial Officer and Treasurer, Sean Cassidy, effective February 29, 2024.
•Announced the appointment of Randy Teel, Ph.D., Arvinas’ current Senior Vice President of Corporate and Business Development and Interim Chief Financial Officer and Treasurer, to the newly created position of Chief Business Officer.
◦Dr. Teel will remain in his interim roles while the Arvinas board of directors continues its search for a permanent Chief Financial Officer and Treasurer.

Anticipated Upcoming Milestones and Expectations
Vepdegestrant
As part of Arvinas’ global collaboration with Pfizer, the companies plan to:
•Complete enrollment and announce topline data for the VERITAC-2 Phase 3 monotherapy trial (ClinicalTrials.gov Identifier: NCT05654623) in patients with metastatic breast cancer (2H 2024).
•Determine the recommended Phase 3 dose of palbociclib to be administered in combination with vepdegestrant from the study-lead in of the VERITAC-3 Phase 3 trial of vepdegestrant and palbociclib as a first-line treatment in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H 2024).
•Continue enrollment of the ongoing Phase 1b/2 clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (TACTIVE-K: ClinicalTrials.gov Identifier: NCT06206837).
•Continue enrollment of the ongoing Phase 1b combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (TACTIVE-U: ClinicalTrials.gov Identifiers: NCTC05548127, NCTC05573555, and NCT06125522).
•Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus atirmociclib, Pfizer’s novel CDK4 inhibitor.

ARV-766
•Following US antitrust regulatory review, currently expected to conclude in Q2 2024, initiate exclusive strategic license agreement with Novartis for the worldwide development and commercialization of ARV-766 and asset purchase agreement for the sale of Arvinas’ preclinical AR-V7 program.

Pipeline
•Continue enrollment in Phase 1 clinical trial in healthy volunteers with PROTAC LRRK2 degrader ARV-102.
•Initiate dosing in first-in-human Phase 1 clinical trial in B-cell lymphomas with PROTAC BCL6 degrader ARV-393 (2Q 2024).

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Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of March 31, 2024, is sufficient to fund planned operating expenses and capital expenditure requirements into 2027.
First Quarter Financial Results
Cash, Cash Equivalents and Marketable Securities Position: As of March 31, 2024, cash, cash equivalents, restricted cash and marketable securities were $1,174.8 million as compared with $1,266.5 million as of December 31, 2023. The decrease in cash, cash equivalents, restricted cash and marketable securities of $91.7 million for the three months ended March 31, 2024 was primarily related to cash used in operations of $92.1 million, unrealized losses on marketable securities of $1.3 million and leasehold improvements of $0.1 million, partially offset by proceeds from the exercise of stock options of $1.8 million.
Research and Development Expenses: Research and development expenses were $84.3 million for the quarter ended March 31, 2024, as compared with $95.3 million for the quarter ended March 31, 2023. The decrease in research and development expenses of $11.0 million for the quarter was primarily due to a decrease in expenses related to our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $8.2 million , our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement) of $2.3 million and our platform and exploratory programs of $0.5 million.
General and Administrative Expenses: General and administrative expenses were $24.3 million for the quarter ended March 31, 2024, as compared with $24.9 million for the quarter ended March 31, 2023. The decrease of $0.6 million was primarily due to a decrease in personnel and infrastructure related costs of $2.4 million, partially offset by an increase in professional fees of $1.3 million and increases related to establishing our commercial operations of $0.6 million.
Revenues: Revenues were $25.3 million for the quarter ended March 31, 2024 as compared with $32.5 million for the quarter ended March 31, 2023. Revenue is related to the Vepdegestrant (ARV-471) Collaboration Agreement, the collaboration and license agreement with Bayer, the collaboration and license agreement with Pfizer, the amended and restated option, license and collaboration agreement with Genentech and revenue related to our Oerth Bio joint venture. The decrease in revenue of $7.2 million was primarily due to a decrease in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement of $12.5 million, a decrease of $1.8 million related to the conclusion of the performance period under the collaboration agreement with Genentech and a decrease of $1.1 million of previously constrained deferred revenue related to our Oerth Bio joint venture, offset in part by year over year increases in revenue of $5.5 million and $2.6 million from our collaboration and license agreements with Bayer and Pfizer, respectively, due to changes in estimates in 2023 of the performance period duration resulting from updated research timelines.

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 ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

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Vepdegestrant has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Preclinically, ARV-766 has demonstrated activity in models of wild type androgen receptor tumors in addition to tumors with AR mutations or amplification, both common potential mechanisms of resistance to currently available AR-targeted therapies.