Johannes Levin (Germany)
MODAG GmbH
Scientific Development
Johannes Levin works as professor for Clinical Neurodegeneration at the Department of Neurology, Ludwig-Maximilians-University Munich and is deputy leader for clinical research at the German Center for Neurodegenerative Diseases (DZNE), site Munich. He has been working in the field of neurodegeneration for 20 years focusing clinically on movement disorders and genetic forms of dementia. The principal research focus is the molecular pathogenesis of neurodegenerative diseases with emphasis on protein aggregation, biomarker development for neurodegenerative diseases and therapy development targeting protein aggregation. Based on this background he joined MODAG GmbH as part-time CMO where he continues his academic work on the oligomer modulator anle138b in an industry setting, where the compound is currently at early stages of clinical development. He has a proven track record for coordinating academic research studies and is principal investigator of the largest interventional trial in Multiple System Atrophy in Germany involving 92 patients at 12 centers (PROMESA trial) with long standing experience in conducting industry sponsored trials. Moreover, he is principal investigator in several national studies and in international cohort studies such as the Dominantly Inherited Alzheimer’s Network (DIAN) and the Genetic Fronto-temporal dementia Initiative (GENFI).

Presenter of 1 Presentation

 Conference Calendar

SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF THE OLIGOMER MODULATOR ANLE138B IN PARKINSON´S DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 1B TRIAL

Session Name
1640 - ADVANCES IN PD AND LBD DRUG DEVELOPMENT 1 (ID 88)
Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 112
Lecture Time
04:00 PM - 04:15 PM
Presenter

Abstract

Aims

Synucleinopathies such as Parkinson ́s disease (PD) and Multiple System Atrophy are characterized by deposition of misfolded and aggregated α-synuclein. Small aggregates (oligomers) of α-synuclein have been shown to be the most relevant neurotoxic species and are targeted by anle138b, an orally bioavailable small molecule compound which shows strong disease-modifying effects in animal models of synucleinopathies. Here we present fist-in-patient data of anle138b in patients with PD.

Methods

Anle138b was studied in a single-centre, double-blind, randomised, placebo-controlled multiple ascending dose (MAD) study in patients with mild to moderate PD. Participants were randomly assigned to placebo or anle138b (dose range 150 mg to 300 mg per day), respectively. The primary endpoints were safety and tolerability, the secondary endpoint was pharmacokinetics. In addition, exploratory endpoints related to pharmacodynamics were assessed and the effect of food on the pharmacokinetics of anle138b was examined. Treatment was administered orally in hard gelatine capsules containing anle138b or excipient only. Clinicaltrials.gov-identifier: NCT04685265. EudraCT-number: 2020-004869-38.

Results

22 participants were enrolled in cohorts A-C. Of these, all completed the study per protocol. There were no major protocol violations. Anle138b demonstrated excellent safety and tolerability at all dose levels. No abnormal trend was seen in any system organ class. Pharmacokinetics of anle138b in PD patients was largely identical to the pharmacokinetics previously observed in healthy volunteers (Clinicaltrials.gov-identifier: NCT04208152).

Conclusions

In patients with PD, anle138b was safe and well tolerated in doses resulting in exposures above the putatively effective plasma levels. These findings warrant long-term efficacy trials in patients with synucleinopathies.

Hide