Arvinas (NASDAQ:ARVN) executives outlined a portfolio shift toward early-stage development and previewed multiple clinical catalysts in a discussion hosted by Barclays biotech analyst Esra Darroudi. Chief Executive Officer Randy Teel and Chief Scientific Officer Angela Cacace said the company is entering 2026 with four Phase 1 programs and expects clinical data for three of those programs during 2026.
Pipeline repositioned around Phase 1 programs
Teel said Arvinas has “repositioned” as a Phase 1-focused company over the past year, with four programs now in Phase 1: a LRRK2 degrader for neurodegenerative disorders, a KRAS G12D degrader for solid tumors, a BCL6 degrader for hematologic malignancies, and a recently initiated trial targeting androgen receptor (AR) with polyglutamine repeats for Kennedy’s disease (also known as spinal and bulbar muscular atrophy).
Vepdegestrant NDA filed; partnership discussions underway
Teel said Arvinas’ previously lead program, vepdegestrant—an estrogen receptor (ER) degrader—had positive pivotal data last year and now has a New Drug Application filed with the FDA. He noted the application has a PDUFA date in early June.
When asked about partnering and commercialization planning, Teel said Arvinas and Pfizer share the goal of making vepdegestrant available quickly if approved. He said partnership discussions are “well on track,” and the companies anticipate completing a deal before the PDUFA date.
Teel also pointed to prior validation for Arvinas’ platform, including an AR degrader for prostate cancer that was out-licensed to Novartis “a couple of years ago.”
LRRK2 program: upcoming Parkinson’s data and PSP plans
Cacace reviewed the rationale for targeting LRRK2, describing it as a multifunctional protein with kinase, GTPase, and scaffolding roles, with accumulation tied to endolysosomal dysfunction and toxic protein buildup in neurodegenerative disease. She said preclinical results showed increased lysosome number and degradative capacity and clearance of pathologic tau, which the company believes could benefit patients with progressive supranuclear palsy (PSP), a tauopathy.
For the company’s LRRK2 degrader program (ARV-102), management said new clinical data would be presented “next week” at the ADPD meeting. Cacace said prior Phase 1 healthy volunteer data showed safety after 14 days of oral dosing and evidence the molecule crossed the blood-brain barrier, with reductions in cerebrospinal fluid (CSF) LRRK2 levels. She also said Arvinas observed reductions in certain CSF proteins elevated in LRRK2-driven Parkinson’s disease, describing these as pathway biomarkers identified through the Michael J. Fox Foundation’s progression marker initiative.
At ADPD, Arvinas expects to share Parkinson’s disease patient data after 28 days of oral dosing, including safety, blood-brain barrier penetration, and evidence of LRRK2 degradation in brain/CSF, along with assessment of pathway biomarkers tied to endolysosomal and neuroinflammatory markers. Cacace said the company believes it has already shown differentiation versus inhibitor approaches by demonstrating greater than 50% CSF LRRK2 degradation and what she characterized as full pathway engagement in CSF in healthy volunteers.
Teel said the company aims to start a Phase 1b trial in PSP patients in the first half of the year and said there may be an opportunity to begin a “registrational quality” study by year-end, contingent on additional steps, including regulatory interactions.
Discussing PSP, Cacace called it a “devastating, life-threatening” disease with mortality typically within five to seven years of diagnosis. She said there are approximately 25,000 diagnosed patients in the U.S. and noted rapid progression can be measured over a year. She also cited the PSP rating scale as a recognized clinical tool used by the FDA.
KRAS G12D degrader: potency and competitive considerations
On KRAS, Cacace said Arvinas’ ARV-806 program works by removing the oncoprotein from tumor cells, contrasting this with “on” and “off” KRAS inhibitors. She said Arvinas’ degrader is “25-fold more potent” than clinical mechanisms the company has evaluated and “40-fold more potent” than another degrader in the clinic, while noting Astellas has shown efficacy with a degrader but is “running up against” liver toxicity. She also said Arvinas does not see the rapid resynthesis response observed with inhibitors, arguing the PROTAC mechanism could support more durable target removal.
Cacace added that some KRAS inhibitors using a cyclophilin “glue-like” mechanism can be immunosuppressive because divarasib inhibits NRAS and HRAS, and said Arvinas has seen “superior combinability” with anti-PD-1 agents in syngeneic models. She also said the company expects good combinability with anti-EGFR inhibitors.
Teel said early Phase 1 dose escalation data will have typical limitations, including small patient numbers, and that initial efficacy evaluation will likely focus on response rate. He emphasized that differentiation could ultimately depend on durability and resistance prevention, but said those aspects may not be visible in an initial update. He also said the Phase 1 trial, which began late last summer, is already fully enrolled, allowing data to come “ahead of where we would have thought.”
BCL6 degrader: 2H data and planned combination study
For ARV-393, Arvinas’ BCL6 degrader, Teel said dose escalation data are expected in the second half of the year. He said the company plans to start a combination study with glofitamab in the coming months, with an aim of moving toward a second-line bispecific setting. Teel said monotherapy performance would need to be in line with what Bristol Myers Squibb has shown, while differentiation may become clearer in combination studies, which he indicated would not read out this year.
Teel also noted that while large B-cell lymphoma is crowded with bispecifics and antibody-drug conjugates, he views the space as less crowded for oral BCL6 options. He added that Arvinas is enrolling patients with T-cell lymphomas in addition to other lymphoma populations.
About Arvinas (NASDAQ:ARVN)
Arvinas, Inc (NASDAQ: ARVN) is a biopharmaceutical company focused on the development of therapies based on targeted protein degradation. Utilizing its proprietary proteolysis-targeting chimera (PROTAC®) platform, Arvinas aims to selectively eliminate disease-causing proteins rather than merely inhibit their activity. This novel approach has the potential to address a range of diseases, including oncology, neurodegeneration and inflammation, by harnessing the body’s natural protein-recycling systems.
The company’s most advanced clinical candidates address hormone-driven cancers.
