Small Molecule · BHV-8000
BHV-8000
Oral, brain-penetrant, highly selective dual inhibitor of tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1), with selectivity over JAK2 and JAK3 to avoid classic JAK-inhibitor safety liabilities. Aimed at neuroinflammation/immune dysregulation across neurodegenerative and neuroinflammatory CNS disorders (Parkinson's, Alzheimer's, ALS, MS, autoimmune encephalitis). Formerly TLL-041; licensed by Biohaven from Hangzhou Highlightll Pharmaceutical (global rights excluding China regions, March 2023).
Also known as: BHV-8000, TLL-041
- Modality
- Small molecule
- Mechanism
- TYK2 inhibitor
- Highest phase
- Phase 2/3
- Lead indication
- Parkinson's disease
- Developer
- Biohaven Ltd. (BHVN)
- Trials
- 1 tracked · 1 recruiting · 15 sites
- Next catalyst
- 2H 2027 — Topline data (Parkinson's disease)
Mechanism of action
Oral, brain-penetrant, highly selective dual TYK2/JAK1 inhibitor that dampens JAK-STAT signaling driven by pro-inflammatory cytokines (e.g., type I interferon / Th17 pathways) in CNS microglia, with selectivity over JAK2 and JAK3. Anti-neuroinflammatory rationale for early Parkinson's disease. Phase 1 showed robust brain penetration (~50% of plasma exposure available as unbound drug in the CNS) and reductions in inflammatory biomarkers (IP-10, hsCRP, IFN-gamma).
| Target | Action | Affinity |
|---|---|---|
| TYK2primaryTYK2 | Inhibitor | —ⓘ |
| JAK1JAK1 | Inhibitor | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| BHV-8000 oral (once-daily) Oral once-daily dosing. Phase 2/3 Parkinson's disease study evaluates 10 mg and 20 mg once daily (up to 48 weeks). Phase 1 studied single doses of 10/20/30 mg and multiple once-daily doses of 6/10/20 mg over 7-14 days. | Oral | Once daily | t½ 12.5 h · Tmax 5 h |
Development timeline
- UpcomingAnticipated Phase 2/3 topline in early Parkinson's disease (primary endpoint: time to first qualifying worsening on MDS-UPDRS Part II)
- First patient enrolled in pivotal Phase 2/3 trial (NCT06976268) in early Parkinson's disease.
- Biohaven acquired exclusive license to BHV-8000 (formerly TLL-041) from Hangzhou Highlightll Pharmaceutical (global rights excluding China regions); planned Phase 1 in 2023. Phase 1 (58 healthy adults) subsequently reported safe/well-tolerated with robust brain penetration and biomarker engagement.↗
BHV-8000 for Parkinson's disease
Phase 2/3RecruitingParkinson's disease indication →
Pivotal global Phase 2/3, randomized, double-blind, placebo-controlled study (NCT06976268 / BHV8000-301) of BHV-8000 10 mg and 20 mg once daily vs placebo in early Parkinson's disease. Primary endpoint: time to first qualifying worsening on MDS-UPDRS Part II (up to 48 weeks). ~550 participants, ages 40-85, across ~185 sites in 13 countries (US, Canada, 11 European nations). First patient enrolled May 2025. NOTE: in March 2026 Biohaven announced a more focused execution plan concentrating on a select number of US sites and deprioritized PD relative to its lead degrader programs.
Readouts
- 2H 2027AnticipatedTopline dataNCT06976268
Anticipated Phase 2/3 topline in early Parkinson's disease (primary endpoint: time to first qualifying worsening on MDS-UPDRS Part II)
Clinical trials
NCT06976268BHV8000-301Phase 2/3Recruitingn=550
A Phase 2/3, Double-Blind, Placebo-Controlled Study of BHV-8000 in Participants With Early Parkinson's Disease
Identifiers
Sources
- A Study to Determine if BHV-8000 is Effective, Safe and Tolerable as a Treatment for Adults Living With Early Parkinson's Disease (NCT06976268) — ClinicalTrials.gov
- BHV-8000, a selective brain-penetrant TYK2/JAK1 inhibitor... demonstrates favorable pharmacokinetics/pharmacodynamics and safety in phase 1 studies (AAN 2025 poster P9-010) — Biohaven Pharmaceuticals / American Academy of Neurology
- Biohaven Acquires Exclusive License for Oral, Brain-Penetrant, Dual TYK2/JAK1 Inhibitor for Immune-Mediated Brain Disorders — Biohaven / PR Newswire