Arvinas Presents Late Breaking, Positive Phase 1 Clinical Data for ARV-102, a PROTAC LRRK2 Degrader, at the 2025 International Congress of Parkinson’s Disease and Movement Disorders®
Arvinas (Nasdaq: ARVN) announced late‑breaking Phase 1 data for ARV-102, an oral brain‑penetrant PROTAC LRRK2 degrader, presented at MDS 2025 on Oct 5, 2025.
The PR states ARV-102 was generally well tolerated (single doses up to 200 mg; multiple daily doses up to 80 mg) with no discontinuations or SAEs. Plasma and CSF exposure increased dose‑dependently, indicating brain penetration. The PR reports >90% PBMC LRRK2 reductions at ≥20 mg and median PBMC reductions of 86% (50 mg) and 97% (200 mg) in patients. In healthy volunteers, 14 days of 80 mg produced CSF proteomic decreases in lysosomal and microglial pathway markers linked to Parkinson’s disease.
Arvinas (Nasdaq: ARVN) ha comunicato dati di fase 1 aggiornati per ARV-102, degrader PROTAC LRRK2 orale in grado di attraversare la barriera emato-encefalica, presentati al MDS 2025 il 5 ottobre 2025.
Il comunicato stampa indica che ARV-102 è stato generalmente ben tollerato (dosaggi singoli fino a 200 mg; dosi multiple quotidiane fino a 80 mg) senza interruzioni o eventi avversi gravi. L’esposizione nel plasma e nel CSF è aumentata in modo dose-dipendente, suggerendo penetrazione cerebrale. Il comunicato riporta riduzioni >90% della LRRK2 nelle PBMC a dosi ≥20 mg e riduzioni medie delle PBMC di 86% (50 mg) e 97% (200 mg) nei pazienti. Nei volontari sani, 14 giorni di 80 mg hanno prodotto diminuzioni proteomiche nel CSF in marker di pathway lisosomiali e microgliali associati alla malattia di Parkinson.
Arvinas (Nasdaq: ARVN) anunció datos de fase 1 de última hora para ARV-102, un degrador PROTAC LRRK2 oral capaz de atravesar el cerebro, presentados en MDS 2025 el 5 de octubre de 2025.
El comunicado indica que ARV-102 fue generalmente bien tolerado (dosis únicas de hasta 200 mg; dosis diarias múltiples hasta 80 mg) sin discontinuaciones ni eventos adversos graves. La exposición en plasma y en CSF aumentó de forma dependiente de la dosis, lo que indica penetración cerebral. El informe de prensa reporta reducciones de >90% de LRRK2 en PBMC a dosis ≥20 mg y reducciones medias de PBMC de 86% (50 mg) y 97% (200 mg) en pacientes. En voluntarios sanos, 14 días de 80 mg produjeron disminuciones proteómicas en CSF en marcadores de rutas lisosomales y microgliales vinculados a la enfermedad de Parkinson.
Arvinas (Nasdaq: ARVN)은 ARV-102에 대한 최종 통신이 막 발표되었으며, 이 약은 뇌를 통과하는 경구용 PROTAC LRRK2 분해제로서 MDS 2025에서 2025년 10월 5일 발표된 초기 1상 데이터입니다.
보도 자료에 따르면 ARV-102는 일반적으로 내약성이 양호했으며(단회 투여 최대 200 mg; 다중 일일 투여 최대 80 mg) 중단이나 중대한 이상반응은 없었습니다. 혈장 및 CSF 노출은 용량 의존적으로 증가하여 뇌 침투를 시사했습니다. PR은 환자에서 ≥20 mg에서 PBMC LRRK2 감소 >90%, 50 mg에서 86%, 200 mg에서 97%의 PBMC 감소를 보고합니다. 건강한 자원자에서 14일 동안 80 mg을 투여하면 파킨슨병과 관련된 리소좀 경로 및 미세글리아 경로 마커의 CSF 단백질체 감소가 나타났습니다.
Arvinas (Nasdaq: ARVN) a publié des données de phase 1 de toute dernière heure pour ARV-102, un dégradeur PROTAC LRRK2 oral capable de traverser la barrière hémato-encéphalique, présentées au MDS 2025 le 5 octobre 2025.
Le communiqué indique qu’ARV-102 a été généralement bien toléré (doses uniques jusqu’à 200 mg; doses quotidiennes multiples jusqu’à 80 mg) sans interruptions ni événements indésirables graves. L’exposition plasmatique et dans le CSF a augmenté de manière dose-dépendante, indiquant une pénétration cérébrale. Le PR rapporte des réductions de LRRK2 dans les PBMC >90% à des doses ≥20 mg et des réductions médianes des PBMC de 86% (50 mg) et 97% (200 mg) chez les patients. Chez les volontaire sains, 14 jours de 80 mg ont produit des réductions protéomiques du CSF dans des marqueurs de voies lysosomales et microgliales liés à la maladie de Parkinson.
Arvinas (Nasdaq: ARVN) gab am späten Tag 1-Daten für ARV-102 bekannt, einen oralen PROTAC-LRRK2-Degrader, der das Gehirn durchdringt, präsentiert auf dem MDS 2025 am 5. Oktober 2025.
Die Pressemitteilung besagt, dass ARV-102 allgemein gut verträglich war (Einzeldosen bis 200 mg; Mehrfachtagsdosen bis 80 mg) mit keinem Abbruch oder schweren unerwünschten Ereignissen. Plasma- und CSF-Exposition stiegen dosisabhängig an, was auf eine Hirnpenetration hindeutet. Die PR berichtet von >90% PBMC LRRK2-Reduktionen bei ≥20 mg und mittleren PBMC-Reduktionen von 86% (50 mg) und 97% (200 mg) bei Patienten. Bei gesunden Freiwilligen führten 14 Tage mit 80 mg zu CSF-Proteom-Reduktionen in Markerpfaden der lysosomalen und mikroglialen Signalwege, die mit der Parkinson-Krankheit in Verbindung stehen.
Arvinas (Nasdaq: ARVN) أعلنت في وقت متأخر من يوم واحد بيانات المرحلة 1 الأخيرة لـ ARV-102، مُحلّل بروتِك LRRK2 فَموي قادر على اختراق الدماغ، والتي عُرضت في MDS 2025 في 5 أكتوبر 2025.
يقول البيان الصحفي إن ARV-102 كان مقبولًا عمومًا من حيث التحمل (جرعات مفردة حتى 200 mg؛ جرعات يومية متعددة حتى 80 mg) دون حدوث توقف أو أحداث جانبية خطيرة. ارتفعت التعرضات في البلازما و< b>CSF بشكل يعتمد على الجرعة، مما يشير إلى اختراق الدماغ. يقول التقرير أن انخفاضات LRRK2 في PBMC تفوق 90% عند جرعات ≥20 mg وارتفاع الانخفاضات الوسطى في PBMC إلى 86% (50 mg) و 97% (200 mg) لدى المرضى. في المتطوعين الأصحاء، أدى إعطاء 80 mg لمدة 14 يومًا إلى انخفاضات بروتوميCSF في مسارات لَيزوسومية وميكروغليالية مرتبطة بمرض باركنسون.
Arvinas (纳斯达克代码：ARVN) 于晚间披露了 ARV-102 的最新阶段1数据，该药为口服、能穿透大脑的 PROTAC LRRK2 降解剂，在 MDS 2025 上于 2025 年 10 月 5 日公布。
新闻稿称 ARV-102 总体耐受性良好（单次剂量最高 200 mg；每日多次剂量最高 80 mg），未有中断或严重不良事件。血浆和 CSF 暴露度呈剂量依赖性增加，表明具备脑 penetrance。报道显示在患者中 ≥20 mg 时 PBMC LRRK2 降幅 >90%，PBMC 降幅中位数为 50 mg 时 86%、200 mg 时 97%。在健康志愿者身上，连续 14 天 80 mg 的治疗产生了 CSF 蛋白质组降幅，涉及与帕金森病相关的溶酶体通路与小胶质通路标志物。
- Well tolerated up to 200 mg; no SAEs or discontinuations
- Dose-dependent CSF exposure indicating brain penetration
- PBMC LRRK2 reductions >90% with repeated daily doses ≥20 mg
- CSF proteomics: reduced lysosomal and microglial markers after 14 days
- Small Parkinson’s trial cohort: 15 treated, 4 placebo
- Reported data are interim/single‑dose; multiple‑dose results pending 2026
Insights
Phase 1 data show ARV-102 is brain‑penetrant, well tolerated, and modulates CSF lysosomal and microglial biomarkers linked to Parkinson’s disease.
What it means: The article reports that ARV-102 produced dose‑dependent exposure in plasma and CSF, indicating brain penetration, and achieved >90% LRRK2 reductions in PBMCs at ≥20 mg and median PBMC reductions of 86% and 97% at 50 mg and 200 mg in patients. The trials showed tolerability with no discontinuations for AEs or SAEs and only mild treatment‑related events in the patient cohort.
Why it matters: Direct CSF exposure plus rapid peripheral target degradation and early CSF proteomic changes provide three distinct, disclosed lines of evidence—pharmacokinetics, pharmacodynamics, and pathway biomarker modulation—that together strengthen the chain of biological activity for a brain‑directed LRRK2 degrader. The reported decreases in lysosomal and neuroinflammatory microglial markers in CSF after 14 days link target engagement to downstream pathways previously observed in LRRK2 Parkinson’s disease, supporting further clinical development.
Notes and near‑term milestones: The article states Arvinas will present multiple‑dose patient data in 2026 and, pending those data and IND clearance, intends to start a Phase 1b trial in progressive supranuclear palsy in the first half of 2026.
– ARV-102 was well tolerated in clinical trials for both healthy volunteers and patients with Parkinson’s disease –
– ARV-102 demonstrated dose-dependent cerebrospinal fluid (CSF) exposure in subjects in both trials –
– After 14 days of treatment in healthy volunteers, ARV-102 decreased lysosomal and neuroinflammatory microglial pathway biomarkers known to be elevated in Parkinson’s disease –
NEW HAVEN, Conn., Oct. 05, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today announced positive pharmacokinetic, pharmacodynamic, and biomarker data from two Phase 1 clinical trials evaluating ARV-102, an oral, brain-penetrant investigational PROTAC degrader of leucine-rich repeat kinase 2 (LRRK2). Results were presented at the International Congress of Parkinson’s Disease and Movement Disorders® (MDS 2025) in Honolulu.
“We are particularly excited by the CSF proteomics results, which demonstrate modulation of lysosomal and microglial pathways that are known to be associated with neurodegenerative diseases,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer of Arvinas. “We believe these findings support the intensified development of ARV-102 in ongoing studies of patients with Parkinson’s disease, and in future studies of patients with progressive supranuclear palsy.”
The company presented data from two trials: ARV-102-101, a first-in-human trial of ARV-102 in healthy volunteers, and ARV-102-103, a trial in patients with Parkinson’s disease. Key findings include:
Data from a Phase 1 Single Ascending Dose and Multiple Ascending Dose Trial in Healthy Volunteers (Poster 904):
- Safety: ARV-102 was generally well tolerated at single doses up to 200 mg and multiple daily doses up to 80 mg, with no discontinuations due to adverse events (AEs) or serious adverse events (SAEs) observed in the study population.
- Pharmacokinetics: ARV-102 exposure increased in a dose-dependent manner in plasma and CSF, the latter indicating brain penetration.
- Pharmacodynamics: Repeated daily doses ≥20 mg resulted in >
90% reductions of LRRK2 protein in peripheral blood mononuclear cells (PBMCs) and >50% reductions in CSF. - Pathway Biomarkers: Repeated daily doses of ARV-102 resulted in reduced plasma concentrations of phospho-Rab10T73 and urine concentrations of bis(monoacylglycerol)phosphate (BMP), a sensitive biomarker for modulation of the lysosomal pathway downstream of LRRK2.
Interim Single Ascending Dose Data from a Phase 1 Trial in Patients with Parkinson’s Disease and CSF Proteomic Data from a Phase 1 Trial in Healthy Volunteers (Late Breaking Abstract #22):
- Safety: The Phase 1 trial in patients with Parkinson’s disease included 15 patients treated with ARV-102 and 4 patients treated with placebo. In the trial, single doses of ARV-102 (50 mg or 200 mg) were well tolerated with only mild treatment-related AEs including headache, diarrhea, and nausea; no SAEs occurred.
- Pharmacokinetics: In patients with Parkinson’s disease, ARV-102 exposure increased in a dose-dependent manner in both plasma and CSF, the latter indicating brain penetration.
- Pharmacodynamics: In patients with Parkinson’s disease, treatment with ARV-102 resulted in median PBMC LRRK2 protein reductions of
86% with the 50 mg dose and97% with the 200 mg dose. - CSF Proteomics: In healthy volunteers treated with ARV-102 80 mg once daily for 14 days, unbiased proteomic analyses of CSF showed significant decreases in lysosomal pathway markers and neuroinflammatory microglial markers previously shown to be elevated in patients with Parkinson's disease harboring LRRK2 variants.
“To our knowledge, this is the first time an investigational LRRK2 therapy has, at 14 days in healthy volunteers, shown effects on distal pathway biomarkers in CSF that are elevated in patients with LRRK2 Parkinson’s disease," said John Houston, Ph.D., Chairperson, Chief Executive Officer, and President at Arvinas. "These data highlight the potential of PROTAC-mediated LRRK2 degradation, encouraging further development that could benefit patients in the future."
Arvinas plans to present initial data from a multiple dose cohort of the Phase 1 clinical trial in patients with Parkinson’s disease (ARV-102-103) in 2026. Pending data from the multiple dose cohort and investigational new drug (IND) clearance, Arvinas intends to initiate a Phase 1b trial in patients with progressive supranuclear palsy in the first half of 2026.
Additional detail on Arvinas’ data presentations at the MDS 2025 Congress:
Poster Title: First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ARV-102, a PROTAC LRRK2 Degrader, in Healthy Participants
- Date & Time: Oct. 7, 12:00-1:00 p.m. HST
- Presentation Order: 3
- Poster Number: 904
Presentation Title: First Clinical Trials of ARV-102, a PROTAC LRRK2 Degrader: Characterization of Pathway Engagement in Healthy Volunteers and Patients With Parkinson’s Disease
- Date & Time: Oct. 8, 12:00-1:00 p.m. HST
- Presentation Order: 11
- Poster Number: Late Breaking Abstract 22
Additional information can be found on the MDS 2025 website.
About ARV-102
ARV-102 is an oral, brain-penetrant investigational PROTAC designed to degrade LRRK2, which is a large, multidomain scaffolding kinase. Increased activity, scaffolding, and expression of LRRK2 have been implicated in the pathogenesis of neurological diseases. LRRK2 mutations are a frequent familial cause of Parkinson’s disease, and common LRRK2 variants have been linked with idiopathic Parkinson’s disease and progressive supranuclear palsy.
About Arvinas
Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC protein degrader platform, Arvinas is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer; ARV-393, targeting B-cell lymphoma 6 protein (BCL6) for relapsed/refractory non-Hodgkin lymphoma; ARV-102, targeting LRRK2 for neurodegenerative disorders; and ARV-806, targeting Kirsten rat sarcoma (KRAS) G12D for cancers harboring this mutation, including pancreatic and colorectal cancer. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding: Arvinas’ belief that the data presented from two Phase 1 clinical trials evaluating ARV-102 (ARV-102-101 and ARV-102-103) supports the intensified development of ARV-102 in ongoing studies of patients with Parkinson’s disease, and future studies of patients with progressive supranuclear palsy; the potential of PROTAC-mediated leucine-rich repeat kinase 2 (“LRRK2”) degradation; the potential of ARV-102, including its degradation of LRRK2 and potential future benefit to patients; Arvinas’ plans to present initial data from a multiple dose cohort of the Phase 1 clinical trial of ARV-102 in patients with Parkinson’s disease; and Arvinas’ intention, pending data from the multiple dose cohort and investigational new drug clearance, to initiate a Phase 1b clinical trial of ARV-102 in patients with progressive supranuclear palsy, and the timing thereof. All statements, other than statements of historical fact, contained in this press release, including statements regarding Arvinas’ strategy, development plans, future operations, prospects, plans and objectives of management and the statements identified in the prior paragraph, are forward-looking statements. The words “ability,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “target,” “goal,” “potential,” “whether,” “will,” “would,” “could,” “reliance,” “should,” “look forward,” “seek,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: whether Arvinas will be able to successfully conduct and complete development for its product candidates, including ARV-102, on its current timelines or at all; risks related to clinical trial results and the interpretation thereof, including with respect to ARV-102; Arvinas’ ability to protect its intellectual property portfolio; Arvinas’ reliance on third parties; whether Arvinas will be able to raise capital when needed; whether Arvinas’ cash and cash equivalents will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2024 and subsequent other reports filed with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release.
Contacts for Arvinas
Investors:
Jeff Boyle
+1 (347) 247-5089
Jeff.Boyle@arvinas.com
Media:
Kirsten Owens
+1 (203) 584-0307
Kirsten.Owens@arvinas.com
FAQ
What Phase 1 ARV-102 safety data did Arvinas report on Oct 5, 2025 for ARVN?
Did Arvinas report brain penetration for ARV-102 (ARVN) at MDS 2025?
What LRRK2 target engagement did Arvinas report for ARV-102 (ARVN)?
What CSF biomarker changes did Arvinas report for ARV-102 at MDS 2025?
When will Arvinas report additional ARV-102 multiple‑dose data and next trials for ARVN?
