Arvinas, Inc. (ARVN) Earnings

Management highlights

### Vepinu (Vepdegastrant) Milestone & Outlicensing - Vepinu, the first ever FDA-approved heterobifunctional PROTAC degrader, received approval for ESR1 mutant ER-positive HER2-negative advanced breast cancer, a population with limited second-line treatment options. - Arvinas entered a global licensing agreement with Rigel Pharmaceuticals for Vepinu's commercialization, development, and manufacturing. Rigel has an established oncology sales infrastructure to rapidly deliver the drug to patients, and the agreement allows Arvinas to focus internal resources on its pipeline of next-generation degraders while maintaining disciplined capital allocation. - Arvinas and Pfizer retain a 50/50 split of all milestones and royalties from the agreement. Arvinas expects to receive an approval milestone and Rigel upfront/near-term milestone payments later in 2026 that will strengthen its cash position. ### Pipeline Progress: Neurodegenerative Programs - **ARV102 (LRRK2 degrader for Parkinson's and progressive supranuclear palsy (PSP))**: Phase 1 data in Parkinson's patients presented at ADPD demonstrated ≥50% LRRK2 reduction in CSF by day 14 (sustained to day 28), which normalizes the ~2-fold LRRK2 elevation seen in Parkinson's. Dose-dependent reductions in neuroinflammation and lysosomal stress biomarkers were observed, with no serious adverse events through 28 days of dosing. These results are not seen with LRRK2 kinase inhibitors. The Phase 1B PSP trial in the U.S. is on clinical hold pending submission of final chronic non-human primate toxicity data (expected mid-2026, trial initiation expected end of 2026). EU trial plans are unchanged, and the global Phase 2 guidance remains on track. PSP is an area of high unmet need with 25,000 affected patients in the U.S. and no approved disease-modifying therapies. ### Pipeline Progress: Oncology Programs - **ARV806 (KRAS G12D degrader)**: Preclinical data shows 25-40x greater potency than clinical-stage KRAS G12D inhibitors/degraders, with >90% durable KRAS degradation for 7 days after a single dose and efficacy across pancreatic, colorectal, and lung cancer models. Dose escalation for the Phase 1 trial was completed ahead of schedule, with rapid enrollment indicating strong investigator interest and unmet need. Initial clinical data will be released later in 2026. - **ARV393 (BCL6 degrader for lymphoma)**: Phase 1 monotherapy dose escalation is ongoing in relapsed/refractory B-cell and T-cell lymphomas. Early responses have been observed at exposure levels lower than predicted to be efficacious, with robust BCL6 degradation despite rapid BCL6 resynthesis. A combination trial with glofitamab for diffuse large B-cell lymphoma has been initiated. Additional data will be shared later in 2026. The program specifically enrolls patients with angioimmunoblastic T-cell lymphoma (AITL), an area of high unmet need, representing a point of differentiation from competing programs. ### Pipeline Progress: Neuromuscular & Discovery Programs - **ARV027 (PolyQ AR degrader for spinal and bulbar muscular atrophy (SBMA/Kennedy's disease))**: The first three cohorts of the Phase 1 single ascending dose trial in healthy volunteers have been enrolled. Preclinical data in an aggressive SBMA mouse model showed PolyQAR degradation in muscle, functional improvements, and extended survival. This program leverages Arvinas' established track record developing AR degraders, and aims to be the first approved disease-modifying therapy for SBMA. - **ARV6723 (HPK1 degrader for immuno-oncology)**: Preclinical data shows deep, sustained degradation of HPK1 (eliminating both its kinase and scaffolding functions, which inhibitors cannot achieve) and stronger single-agent anti-tumor activity than HPK1 inhibitors and anti-PD-1 across multiple tumor types, including activity in 7 checkpoint-resistant models. The program reverses immunosuppressive tumor microenvironments by impacting the myeloid compartment, and is on track to enter the clinic in late 2026. - **Oral pan-KRAS PROTAC program**: The program achieves broad degradation of KRAS across multiple alterations (including wild-type amplified KRAS) with selectivity over other RAS isoforms, acting on both on and off signaling states. Preclinically, it shows stronger anti-proliferative activity and greater synergy with anti-PD-1 than investigational pan-RAS inhibitors, and complements the ARV806 KRAS G12D program. More updates will be shared later in 2026.

Guidance

- Arvinas maintains its cash runway guidance into the second half of 2028, which will allow funding of operations through all key upcoming pipeline data milestones. - The ARV102 Phase 1B PSP trial in the U.S. is expected to initiate by the end of 2026, with no change to the planned global Phase 2 start guidance. A potential registrational trial for ARV102 in PSP is expected to start in the second half of 2026. - Initial clinical data for ARV806 (KRAS G12D degrader) and additional data for ARV393 (BCL6 degrader) will be released later in 2026. - ARV6723 (HPK1 degrader) is on track to enter the clinic in late 2026. - Additional updates for the pan-KRAS PROTAC program will be provided later in 2026.

Segment performance

As a clinical-stage biotech, Arvinas reports consolidated financial results rather than separate product segment performance. For Q1 2026: total revenue was $15.6 million, down from $188.8 million in Q1 2025 (the decrease was driven by reduced revenue recognition from the Vepdegastrant collaboration agreement with Pfizer due to changes in estimated remaining program costs). General & administrative (G&A) expenses were $19.1 million, down from $26.6 million YoY. Research & development (R&D) expenses were $60.3 million, down from $90.8 million YoY. Non-GAAP R&D expenses decreased 32% ($25 million) YoY, Non-GAAP G&A expenses decreased 44% ($10.1 million) YoY. Total Non-GAAP expenses were $67.3 million, a $35.1 million decrease YoY, reflecting the company's completed cost reduction program. Cash, cash equivalents, and marketable securities totaled $614.9 million at the end of Q1 2026, down from $685.4 million at the end of 2025.

Risks & headwinds

- The U.S. Phase 1B trial of ARV102 in PSP is currently on clinical hold, as the FDA requested final chronic toxicity study data from non-human primates that was not originally requested, which will delay U.S. trial initiation until the end of 2026. - The KRAS targeted therapy space is highly competitive and rapidly evolving, with multiple clinical-stage programs already advancing, which creates pressure on Arvinas to demonstrate differentiated efficacy and tolerability to compete successfully. - Early clinical data for pipeline programs is not predictive of eventual success, and there is no guarantee that observed preclinical and early clinical biomarker/response signals will translate to clinically meaningful efficacy in later-stage trials. - Vepinu future global regulatory filings and expansion beyond the U.S. are dependent on Rigel's resources and priorities, which are outside of Arvinas' direct control.

Analyst Q&A

• Q: How are Rigel partnership revenue split between Arvinas and Pfizer, and what development costs will Rigel cover? /

  A: Arvinas and Pfizer have an equal 50/50 split of all milestones and royalties from the Rigel outlicensing agreement. Rigel holds global rights, but current public deal terms primarily pertain to the U.S. where Vepinu just received approval, as Rigel will need to secure additional international partners for ex-U.S. launch. Rigel will contribute $40 million to offset costs of ongoing Vepinu development activities.

• Q: What data will be released for ARV806 later this year, and how translatable is ARV027's mouse model data to humans? /

  A: ARV806 data release will include safety, pharmacokinetics, pharmacodynamics, and initial response rate data. Data released later in the year will include more durability data, which is the most important endpoint for comparative assessment. For ARV027, Arvinas has extensive clinical experience degrading androgen receptors, and the degrader was specifically designed to target polyQ-expanded AR in muscle. Preclinical data in aggressive SBMA mouse models showed dose-dependent target degradation and rescued key disease endophenotypes (endurance and strength). The Phase 1 trial in healthy volunteers primarily aims to confirm target engagement in muscle to support translation to patients.

• Q: Why did Arvinas prioritize PSP over Parkinson's for ARV102's next trial step, and what is the rationale for testing two doses in ARV806 Phase 2 expansion? /

  A: PSP has extremely high unmet need, with no approved disease-modifying therapies, a homogeneous rapidly progressing patient population that allows smaller, shorter trials to read out treatment effects, and less competition than Parkinson's. The biomarker learning from the Parkinson's Phase 1 trial directly transfers to PSP, allowing rapid selection of a dose range for the PSP trials. Testing two doses in ARV806 Phase 2 expansion is standard oncology practice: it allows Arvinas and the FDA to confirm the optimal dose based on a full set of factors including overall response rate, target degradation level, and safety profile.

• Q: What differentiation does Arvinas's pan-KRAS degrader have relative to existing pan-RAS inhibitors, especially in combination with anti-PD-1? /

  A: Existing investigational pan-RAS inhibitors target all RAS isoforms (NRAS, HRAS, KRAS) which leads to higher toxicity, particularly skin toxicity, that limits dosing and combination use. Arvinas's pan-KRAS degrader is selective for KRAS only, which is expected to reduce off-target toxicity and enable more effective combination therapy. Mechanistically, unlike pan-RAS inhibitors, the pan-KRAS degrader does not inhibit T-cell function. It increases tumor antigenicity and remodels the immunosuppressive tumor microenvironment, leading to greater synergy with anti-PD-1 and higher complete response rates in preclinical models.