Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders
-Data from initial cohorts suggest that Arvinas’ PROTAC® platform has the potential to create safe and well-tolerated orally bioavailable drugs for the treatment of certain cancers
-Conference call to be held at
“This is the first look at clinical data from our PROTAC® platform and is an exciting milestone for both
Phase 1 Study Designs and Clinical Data
Both ARV-110 and ARV-471 are being evaluated in Phase 1, open-label, dose-escalation clinical trials designed to assess safety, tolerability, and pharmacokinetics (PK).
The ARV-110 clinical trial is of 28 to 36 patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on at least two prior systemic therapies. The ARV-471 clinical trial is of 24 to 36 patients with estrogen receptor positive (ER+) / human epidermal growth factor receptor-2 negative (HER2-) locally advanced or metastatic breast cancer who have received prior hormonal therapy and chemotherapy.
Both ARV-110 and ARV-471 are oral therapies dosed once per day.
The presentation today will show that Arvinas’ PROTAC® protein degraders have been well tolerated by patients at the doses tested to date. The initial data for ARV-110 are from the first three dose-escalation cohorts (35 mg, 3 patients; 70 mg, 4 patients; and 140 mg, 3 patients), while the initial data presented for ARV-471 are from three patients enrolled in the first dose cohort (30 mg). Both ARV-110 (35, 70, and 140 mg) and ARV-471 (30 mg) were well tolerated, with no dose-limiting toxicities (DLTs) and no grade 2, 3, or 4 related adverse events observed.
The presentation today will also show dose proportionality for ARV-110 and that exposures of both ARV-110 and ARV-471 have reached levels associated with tumor growth inhibition in preclinical studies. For both programs and at each dose level tested to date, PK data were evaluated at days 1 and 15 following initial dosing. The third (140 mg) cohort of ARV-110 and the first (30 mg) cohort of ARV-471 reached average plasma exposures and average maximum concentrations that were above the lower ends of the ranges that were associated with tumor growth inhibition in preclinical studies. In addition, increases in exposure and average maximum concentration of ARV-110 were dose-proportional across all three doses tested to date.
For the next cohorts of each of ARV-110 and ARV-471, the dose is being increased by 100% (to 280 mg for ARV-110, and to 60 mg for ARV-471). Aside from continuing to investigate safety and PK, the Phase 1 clinical trial of ARV-110 will also evaluate biochemical and clinical activity by assessing prostate specific antigen (
The company will host a conference call and webcast at
ARV-110 is an orally-bioavailable PROTAC® protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer (mCRPC). Arvinas’ Phase 1 trial of ARV-110 will assess its safety, tolerability, and pharmacokinetics, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.
ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.
ARV-471 is a PROTAC® protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of women with metastatic breast cancer. Arvinas’ Phase 1 trial of ARV-471 will assess its safety, tolerability, and pharmacokinetics, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.
In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity as a single agent and in combination with a CDK4/6 inhibitor when compared to a standard of care agent, fulvestrant (as a single agent and in combination with a CDK4/6 inhibitor).
This press release contains forward-looking statements that involve substantial risks and uncertainties, including statements regarding the development and regulatory status of our product candidates, such as statements with respect to our lead product candidates, ARV-110 and ARV-471, and the timing of clinical trials and data from those trials for our product candidates, and our discovery programs that may lead to our development of additional product candidates, the potential utility of our technology and advantages and therapeutic potential of our product candidates, and the sufficiency of our cash resources. All statements, other than statements of historical facts, contained in this press release, including statements regarding our strategy, future operations, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make as a result of various risks and uncertainties, including but not limited to: whether we will be able to successfully conduct Phase 1 clinical trials for ARV-110 and ARV-471, complete other clinical trials for our product candidates, and receive results from our clinical trials, on our expected timelines, or at all, whether our cash resources will be sufficient to fund our foreseeable and unforeseeable operating expenses and capital expenditure requirements on our expected timeline and other important factors discussed in the “Risk Factors” sections contained in our quarterly and annual reports on file with the
Will O’Connor, Stern Investor Relations
Source: Arvinas Inc.