Executives from Arvinas (NASDAQ:ARVN) outlined recent pipeline progress and upcoming catalysts at TD Cowen’s 46th Annual Healthcare Conference, highlighting a growing set of Phase 1 programs built on what the company described as a “pivotal trial-proven” protein degradation platform.
Dr. Randy Teel, Arvinas’ President and CEO, and Chief Scientific Officer Angela Cacace said the company now has four Phase 1 programs in the clinic and expects to have five by year-end. Teel also noted the company “just announced last week” it began dosing a fourth Phase 1 program—an androgen receptor (AR) degrader.
Platform and current clinical footprint
He cited ongoing clinical programs including:
- ARV-102, a LRRK2 degrader in neurodegeneration
- ARV-806, a KRAS G12D degrader in solid tumors
- ARV-393, a BCL6 degrader in hematology
- ARV-027, a newly initiated AR degrader program
Separately, Teel referenced a partnership with Novartis involving an AR degrader, luxdegalutamide, which he said is advancing in multiple combination trials in castrate-sensitive and castrate-resistant prostate cancer.
LRRK2 degrader: Phase 1 biomarker focus and upcoming ADPD update
On the neurodegeneration program, Teel said Arvinas’ LRRK2 degrader is being evaluated in two Phase 1 studies: one in healthy volunteers and another in Parkinson’s disease patients. He said the next readout from the Parkinson’s Phase 1 trial is expected “in just a couple of weeks” at the ADPD conference in Copenhagen.
Cacace explained the rationale for degradation over kinase inhibition, describing LRRK2 as a large multi-domain kinase with scaffolding function, GTPase activity, and kinase activity. She said a degrader can remove the entire protein and therefore all of those activities, while mutations occur across the protein and contribute to pathological endolysosomal activity implicated in neurodegeneration.
Discussing healthy volunteer results, Cacace said Arvinas’ goal was to demonstrate that “the first PROTAC in neurodegeneration could actually cross the blood-brain barrier.” She said the company showed dose-dependent cerebrospinal fluid (CSF) exposure and dose-dependent reduction of LRRK2 in CSF. She also said the company demonstrated pathway engagement, citing reductions in LRRK2-driven proteins in CSF that had been shown to be elevated in LRRK2-driven Parkinson’s disease.
Looking ahead, Cacace said Parkinson’s patient data will focus on confirming LRRK2 reduction and engagement of the same LRRK2-driven pathway in an older, diseased population, with attention to neuroinflammatory and endolysosomal markers. She added that Arvinas believes it has already shown pathway effects in a 14-day healthy volunteer study “something that inhibitors have not been able to show.”
On translating Parkinson’s learnings to progressive supranuclear palsy (PSP), Cacace cited findings that genetics and endolysosome biomarkers are upregulated in PSP and that LRRK2 is elevated roughly twofold, alongside clinically meaningful progression on the PSP rating scale within a year. She said these factors support a therapeutic hypothesis for PROTAC-mediated reduction of LRRK2. Teel added the plan is to move into PSP after Phase 1, and Cacace said the company is “waiting for regulatory” as it heads toward a Phase 1 study.
ARV-027: targeting mutant androgen receptor in SBMA
Teel described ARV-027 as Arvinas’ third AR degrader to enter the clinic, following ARV-110 (first dosed in 2019) and a second-generation AR degrader licensed to Novartis. He said ARV-027 is designed to degrade polyglutamine repeat AR, which is known to drive spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease. Teel said the clinical study in healthy volunteers began “in the past few weeks.”
Cacace pointed to preclinical data in an aggressive SBMA model, saying ARV-027 degraded polyglutamine repeat AR in muscle and rescued muscular atrophy, grip strength, endurance, and prolonged survival. She also cited results in human iPSC-derived skeletal muscle supporting translational relevance. Addressing preservation of normal androgen signaling, Cacace noted SBMA is an X-linked disorder where “all of the receptor is actually mutant,” and said the goal is to reduce receptor-driven toxicity and dysfunction observed in preclinical work.
Oncology: vepdegestrant partnering and wholly owned programs
In breast cancer, Teel addressed the lead program vepdegestrant ahead of a June 5 PDUFA date in ESR1-mutant, second-line breast cancer. He said Arvinas’ priority is to get the drug to patients quickly if approved and reiterated a view that it could be “best-in-class.” On commercialization, he said the company is working with Pfizer to secure a partner and believes it is “on track to get it done by early June,” adding there has been “good interest” and that an announcement will come when ready. Asked about alternatives if no partner is secured, Teel said those discussions are not active given current partnering progress, while noting Pfizer has capabilities that could be used.
On ARV-393 (BCL6), Teel described BCL6 as a historically difficult target and said Arvinas is running a Phase 1 dose escalation study, with an aim to move into diffuse large B-cell lymphoma (DLBCL). He said the company is enrolling both B-cell and T-cell lymphoma patients and, while no “official data releases” have been made, Arvinas previously commented it has seen initial responses in both groups and “good, robust degradation” of BCL6, which he described as rapidly resynthesized. Teel said an official first-in-human data release is expected in the second half of the year.
Cacace argued degradation is superior to inhibition for BCL6 due to rapid resynthesis, saying ARV-393 maintains greater than 90% reduction and drives durable tumor growth suppression, while inhibitors have not reached the clinic.
Teel also said Arvinas is preparing to begin a Phase 1 combination study of ARV-393 with glofitamab “very soon.” He added the company is focused on creating a “chemo-free” option and highlighted potential differentiation in the T-cell lymphoma setting, where he said options are limited after initial failures. Cacace added that preclinical work shows increases in CD20, interferon signaling, and antigen presentation, which she said supports combinability.
KRAS G12D: enrollment complete; first clinical data expected in 2026
Teel said ARV-806, Arvinas’ KRAS G12D degrader, began Phase 1 enrollment last summer and has enrolled quickly. He said the company “just announced last week” that enrollment has been completed. While Arvinas has guided to initial clinical data in 2026, Teel said he would not necessarily expect that to come at the very end of the year.
He emphasized that early dose-escalation readouts can provide signals such as response rate, but that differentiation may ultimately depend on durability, tolerability, safety, and combinability as the program advances into dose expansion at exposures expected to be efficacious.
Cacace discussed preclinical comparative pharmacology shared at the “Triple Meeting,” saying Arvinas observed 25-fold greater effectiveness in inhibiting proliferation compared with “the clinical mechanisms” evaluated, and highlighted effects including Myc reduction across the dosing interval, increased apoptotic markers, induction of tumor microenvironment MHC antigenicity in syngeneic models, and favorable combinability with a pan-RAS(ON) inhibitor. Teel added that competitors have shown response rates “something like 35% ORRs” and said Arvinas’ early clinical goal is to be competitive, while broader differentiation will be assessed later.
Finally, Cacace noted Arvinas is also developing a pan-RAS degrader in preclinical work, describing efforts to address additional KRAS mutation variants and KRAS amplification as a resistance mechanism. Teel said near-term upcoming clinical updates begin with ARV-102, followed by KRAS, then ARV-393, with newer programs like ARV-027 earlier in development.
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.
