• Major milestone in development of novel treatment for progressive supranuclear palsy and other tau-related dementias

Asceneuron SA, an emerging leader in the development of innovative small molecules for the treatment of neurodegenerative diseases, announced today it has commenced a new clinical trial of its lead asset, ASN120290. The study aims to quantify target engagement of ASN120290 in the human brain using positron emission tomography (PET) to help guide dose selection for a planned clinical efficacy trial in PSP.  ASN120290 has the potential to become a first-in-class treatment for progressive supranuclear palsy (PSP), a rapidly progressing rare neurodegenerative disorder, and other tau-related dementias.

ASN120290 is a selective inhibitor of the O-GlcNAcase enzyme and was recently granted Orphan Drug Designation by the US Food and Drug Administration (FDA) for the treatment of PSP. Its therapeutic potential has been demonstrated in preclinical studies with a profound reduction in the accumulation of toxic aggregates of the tau protein into neurofibrillary tangles. Neurofibrillary tangles are now widely recognized as the main cause of neurodegeneration and clinical symptoms in the majority of dementia cases, including Alzheimer’s disease (AD). 

Dirk Beher, Chief Executive Officer and Founder of Asceneuron, commented: “The application of PET imaging to demonstrate that a drug molecule reaches its intended therapeutic target in the brains of living human beings has become best practice in CNS drug discovery. PET imaging provides tremendous value to accelerate clinical development programs. The PET imaging data will be critical for dose selection in subsequent studies with ASN120290. We are excited about this new clinical trial with ASN120290 which demonstrates our continuing commitment to bring urgently needed treatments to patients with PSP and other tau-related neurodegenerative diseases.” 

PET imaging is a non-invasive method to quantify the binding of ASN120290 to the O GlcNAcase enzyme in the living human brain. In this study, a specific enzyme inhibitor-derived imaging agent (PET tracer) will be administered either alone or after a pre-dose of ASN120290 in healthy volunteers. Once the PET tracer is introduced into the bloodstream, it crosses the blood-brain barrier and binds directly to the O-GlcNAcase enzyme inside brain cells. When ASN120290 is given prior to the tracer, it binds to the same enzyme in the brain thereby blocking the binding of the subsequently administered PET tracer. This decrease of PET tracer binding can be quantified, thereby allowing to calculate O-GlcNAcase enzyme occupancy by ASN120290.

Asceneuron SA, an emerging leader in the development of innovative small molecules for the treatment of neurodegenerative diseases, announced today that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to ASN120290 for the treatment of progressive supranuclear palsy (PSP), a rapidly progressing rare neurodegenerative disorder. ASN120290 was discovered at Asceneuron and is a selective inhibitor of the O-GlcNAcase enzyme. Based on its unique mechanism of action, the molecule has the potential to become a first in class treatment for PSP and other tau-related dementias.

ASN120290 has recently completed a randomized, double-blind, placebo-controlled phase I study to assess its safety and tolerability of single and multiple doses in healthy young and elderly volunteers. Data from that study will be presented at the upcoming Alzheimer’s Association International Conference (AAIC) to be held in Chicago July 22-26, 2018.

The therapeutic potential of ASN120290 has been demonstrated in preclinical studies with a substantial reduction in the build-up of toxic aggregates of tau into neurofibrillary tangles. Neurofibrillary tangles are widely recognized as a key driver of neurodegeneration and clinical symptoms in the majority of dementia cases, including Alzheimer’s disease.

PSP is a rare neurological condition that causes severe problems with walking, balance, speech, swallowing and vision as a result of the accumulation of aggregates of the tau protein in the brain. It is estimated that three to six people per 100,000 will develop PSP and there is currently no cure for the disease.

Dirk Beher, chief executive officer and a founder of Asceneuron, commented: “PSP is a rare neurological condition for which there is currently no treatment available. ASN120290 is an orally bioavailable molecule that has the potential of treating the root cause of the neurodegeneration. The granting of Orphan Drug Designation for ASN120290 by the FDA is an important milestone for the team and the company. It strengthens our commitment to serving this important unmet medical need and bringing this molecule to patients.”

Orphan Drug status is intended to advance drug development for rare diseases. The FDA provides Orphan Drug Designation to drugs and biologics that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions that affect fewer than 200,000 people in the U.S. The designation can provide development and commercial incentives for designated compounds and medicines, including eligibility for a seven-year period of market exclusivity in the U.S. after product approval, FDA assistance in clinical trial design and an exemption from FDA user fees.