On October 23, 2019 Arvinas, Inc., (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported a platform data update that includes initial safety, tolerability, and pharmacokinetic data from the company’s ongoing Phase 1 clinical trials of ARV-110 and ARV-471 (Press release, Arvinas, OCT 23, 2019, View Source [SID1234542433]). The data, which show dose-proportional exposures of ARV-110 and that both ARV-110 and ARV-471 have been well tolerated, will be presented by Ian Taylor, Ph.D., Chief Scientific Officer at Arvinas, at the 2nd Targeted Protein Degradation Summit in Boston, MA. Dr. Taylor’s presentation will be available on Arvinas’ website this morning.

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"This is the first look at clinical data from our PROTAC platform and is an exciting milestone for both Arvinas and for the field of targeted protein degradation. We are seeing a favorable overall safety profile for both clinical programs to date, and dose-proportional exposures of ARV-110," said John Houston, Ph.D., Chief Executive Officer at Arvinas. "We are encouraged by these initial results as we work to create well tolerated therapies to treat serious diseases."

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 (PSA) levels and RECIST response in patients with baseline measurable disease, androgen receptor (AR) degradation, and other exploratory biomarkers. The Phase 1 clinical trial of ARV-471 will continue to evaluate safety and PK, as well as evaluate estrogen receptor (ER) degradation, RECIST response in patients with baseline measurable disease, and other exploratory biomarkers.

Arvinas expects to next share clinical data from the Phase 1 dose escalation trial of ARV-110 in the first half of 2020 and from the Phase 1 dose escalation trial of ARV-471 in the second half of 2020.

Conference Call:
The company will host a conference call and webcast at 8:30 AM ET today to discuss these initial data. Participants are invited to listen by dialing (844) 467-7654 (domestic) or (602) 563-8497 (international) five minutes prior to the start of the call and providing the passcode access code 9096099. A listen-only webcast of the conference call can also be accessed through the "Investors" tab on the Arvinas website, www.arvinas.com, and a replay will be available for six weeks following the call.