Small Molecule · Emrusolmin

Emrusolmin

Phase 2Teva Pharmaceutical Industries Ltd. (TEVA)
  • Orphan Drug
  • Fast Track

Oral, brain-penetrant small-molecule oligomer modulator (anle138b; TEV-56286). A diphenyl-pyrazole [3-(2H-1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole] identified by high-throughput screening for inhibitors of alpha-synuclein and prion-protein oligomerization; it binds and modulates pathological protein aggregates (alpha-synuclein, and also reported tau/prion) to slow oligomer accumulation and neurodegeneration. Discovered/originated by MODAG GmbH (Germany); exclusively licensed to and developed by Teva (collaboration announced October 2021) for multiple system atrophy and Parkinson's disease. CAS 882697-00-9; C16H11BrN2O2.

Also known as: Emrusolmin, 882697-00-9, TEV-56286, anle138b, 3-(2H-1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole

Data current as of

Key facts

Modality
Small molecule
Chemical class
pyrazole, Benzodioxole
Chemistry
Achiral
Mechanism
Alpha-synuclein modulator
Highest phase
Phase 2
Lead indication
Multiple System Atrophy
Developer
Teva Pharmaceutical Industries Ltd. (TEVA)
Designations
Orphan Drug, Fast Track
Trials
1 tracked · 1 recruiting
Next catalyst
2H 2027 — Topline data (Multiple System Atrophy)

Mechanism of action#

Oral, brain-penetrant small-molecule 'oligomer modulator' that binds pathological alpha-synuclein aggregates and interferes with their oligomerization/formation, reducing accumulation of toxic oligomeric species. In MSA (an alpha-synucleinopathy with oligodendroglial alpha-synuclein inclusions), the disease-modifying rationale is modulation of pathological alpha-synuclein. The compound (anle138b) also binds aggregated tau and prion protein in preclinical work, but the MSA program targets alpha-synuclein. Preclinical MSA models showed reduced alpha-synuclein oligomerization, prevented motor decline and neurodegeneration; excellent oral bioavailability and blood-brain-barrier penetration.

TargetActionAffinity
Alpha-synucleinprimarySNCAModulator—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Emrusolmin oral (300 mg once daily)
300 mg orally once daily (Phase 2 TOPAS-MSA dose); Phase 1 tested single/multiple ascending doses up to 300 mg/day
OralOnce dailyt½ 12 h

Development timeline#

202220232024202520262027TodayPhase 126 Oct 2021 — Licensing deal — Teva in-licenses anle138b (emrusolmin / TEV-56286) from MODAG1 Oct 2021 — phase change — MODAG GmbH and Teva announced an exclusive worldwide licensing collaboration to develop anle138b (and related sery433) for MSA and Parkinson's disease (October 2021). Earlier first-in-human Phase 1a (healthy volunteers) and a Phase 1b multiple-ascending-dose study in Parkinson's disease (150-300 mg/day) were conducted by MODAG; exact NCT/dates not re-verified here so summarized without fabrication. changed_at is approximate to the licensing announcement (month-level).Phase 215 Sept 2027 — upcoming — Anticipated Phase 2 (TOPAS-MSA) topline in multiple system atrophy (primary endpoint: change from baseline in UMSARS at week 48)2 Oct 2024 — phase change — Phase 2 TOPAS-MSA (NCT06568237) initiated; study start date 2024-10-02 (actual) per ClinicalTrials.gov; recruiting in MSA.
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Oct 2024 – Sept 2027
  1. UpcomingAnticipated Phase 2 (TOPAS-MSA) topline in multiple system atrophy (primary endpoint: change from baseline in UMSARS at week 48)
  2. Phase 2 TOPAS-MSA (NCT06568237) initiated; study start date 2024-10-02 (actual) per ClinicalTrials.gov; recruiting in MSA.
Phase 1Oct 2021 – Oct 2021
  1. Licensing dealTeva in-licenses anle138b (emrusolmin / TEV-56286) from MODAG↗
  2. MODAG GmbH and Teva announced an exclusive worldwide licensing collaboration to develop anle138b (and related sery433) for MSA and Parkinson's disease (October 2021). Earlier first-in-human Phase 1a (healthy volunteers) and a Phase 1b multiple-ascending-dose study in Parkinson's disease (150-300 mg/day) were conducted by MODAG; exact NCT/dates not re-verified here so summarized without fabrication. changed_at is approximate to the licensing announcement (month-level).↗

Emrusolmin for Multiple System Atrophy#

Phase 2RecruitingMultiple System Atrophy indication →

Phase 2 (TOPAS-MSA, NCT06568237): multi-center, double-blind, randomized, placebo-controlled, parallel-group study of oral once-daily emrusolmin (TEV-56286) vs placebo in adults with multiple system atrophy. 48-week double-blind treatment; ~350 participants; primary endpoint change from baseline in Modified UMSARS Part I (non-EU sites) / Total UMSARS (EU sites) at week 48. FDA Orphan Drug designation granted 2022; FDA Fast Track designation granted 2025-09-09. Lead/sole disclosed indication for emrusolmin's pivotal-track development under Teva (PD explored in earlier Phase 1b).

Readouts

  • 2H 2027AnticipatedTopline dataNCT06568237

    Anticipated Phase 2 (TOPAS-MSA) topline in multiple system atrophy (primary endpoint: change from baseline in UMSARS at week 48)

Clinical trials#

NCT06568237TV56286-NDG-20039Phase 2Recruitingn=350

A Multi-centered, Double-blind, Randomized, Placebo-controlled, Parallel Group Phase 2 Study of TEV-56286 for the Treatment of Patients With Multiple System Atrophy (TOPAS-MSA)

Started Oct 2024· Primary completion Sept 2027

Sources#

  1. A Trial to Test if TEV-56286 is Effective for Treatment of Participants With Multiple System Atrophy (TOPAS-MSA) (NCT06568237) — ClinicalTrials.gov
  2. Anle138b modulates alpha-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy — Movement Disorders (PMC6492169)
  3. Emrusolmin — Therapeutics — ALZFORUM
  4. Teva and MODAG Announce Licensing Collaboration for Neurodegenerative Disease Drug Candidate — Teva
  5. Teva and MODAG Announce Licensing Collaboration for Neurodegenerative Disease Drug Candidate — Teva / MODAG (Business Wire)