Asceneuron Publishes Pioneering Preclinical Efficacy Data on its Novel Clinical Molecule ASN90 in Both Alzheimer's and Parkinson's Disease Models

• Findings published in the peer-reviewed journal ACS Chemical Neuroscience demonstrated increased survival in preclinical model of Alzheimer's disease after administration of clinical molecule ASN90, as well as significant motor impairment and astrogliosis effect in a Parkinson's model
• Unique functional benefits in gold-standard preclinical models of Alzheimer's and Parkinson's disease highlight the significant potential of O-GlcNAcase inhibitors for disease modification

LAUSANNE, Switzerland and SAN FRANCISCO, April 1, 2022 /PRNewswire/ -- Asceneuron SA, a clinical stage company dedicated to targeting the root causes of neurodegenerative diseases, today announces the publication of peer-reviewed data in the journal ACS Chemical Neuroscience regarding ASN90, an O–GlcNAcase (OGA) inhibitor, and one of its leading candidates in clinical development for treating neurodegenerative proteinopathies.

Neurodegenerative proteinopathies such as Alzheimer's and Parkinson's disease are characterized by the intracellular formation in the brain of insoluble and toxic protein aggregates, such as the microtubule-associated protein tau and α-synuclein respectively, that are closely linked to disease progression. OGA is an emerging drug target in central nervous system drug development since deficient glycosylation of these intracellular proteins has been associated with neuronal dysfunction. OGA inhibitors prevent the elimination of intracellular protein glycosylation, thereby halting the decline of the healthy-state levels of this post-translational modification and preventing the formation of toxic protein aggregates.

In this recently published, peer-reviewed paper, Asceneuron reports the preclinical discovery and development of the novel small molecule OGA inhibitor ASN90 (formerly known as ASN120290/ASN561), which has already completed testing in three Phase I studies in healthy young and elderly subjects. The preclinical data show that daily oral administration of ASN90 prevented the development of tau tangle pathology, as well as functional deficits in motor behavior and breathing, and increased survival. Another significant finding; novel for this class of molecules; is that ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized, preclinical model of Parkinson's disease.

Asceneuron currently has an open investigational new drug (IND) application with the US Food and Drug Association (FDA) for a Phase 2/3 study to evaluate ASN90 in progressive supranuclear palsy (PSP), an orphan indication. 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. The disease gets progressively worse, with people becoming severely disabled within three to five years of onset. 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, Co-Founder of Asceneuron and senior author of the study, commented: "We are very excited to publish such key encouraging preclinical data on ASN90 and OGA mechanism of action. These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies such as Alzheimer's, PSP, and Parkinson's disease. Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for multiple indications. We continue to progress our clinical development with our latest once a day OGA inhibitor, ASN51, which will be dosed in Alzheimer's disease patients in the forthcoming months."

The article has been published online ahead of print and can be found here: O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies

About Asceneuron

Asceneuron is a clinical stage biotech company focused on the development of orally bioavailable therapeutics for debilitating neurodegenerative disorders with high unmet medical need. The pipeline reflects our ambition to develop treatments for a wide a range of neurodegenerative diseases including orphan tauopathies, Alzheimer's and Parkinson's disease. Asceneuron has two clinical stage small molecule O-GlcNAcase inhibitors in development for the treatment of proteinopathies including one first in class for Parkinson's disease, one best in class in Alzheimer's disease and related disorders.

Asceneuron is a privately held company financed by a renowned syndicate of investors consisting of Sofinnova Partners, M Ventures, SR One, Johnson & Johnson Innovation – JJDC, Inc. (JJDC) and Kurma Partners. For more information, please visit www.asceneuron.com.

About ACS Chemical Neuroscience

ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical, and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. https://pubs.acs.org/journal/acncdm

About ASN51

Asceneuron's best-in-class program ASN51, a next-generation O-GlcNAcase inhibitor, was awarded USD 2.2 million from the Alzheimer's Drug Discovery Foundation for a first in human Phase I study. The trial in progress recruits healthy volunteers and Alzheimer's disease patients at sites in Europe and Australia and began in Q2 2021. Asceneuron will be presenting results at the upcoming conferences on safety, tolerability, pharmacokinetics, and human target engagement in healthy volunteers.

About ASN90

Asceneuron's most clinically advanced program ASN90 (formerly labelled as ASN120290) is an O–GlcNAcase inhibitor and is being developed for the orphan tauopathic disease, progressive supranuclear palsy (PSP), after receiving Orphan Drug Designation by the US FDA for the treatment of PSP. ASN90 has 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 were presented at the Alzheimer's Association International Conference (AAIC) in Chicago July 22-26, 2018.