ASN51 / Asceneuron - LARVOL DELTA

Study of ASN51 in Adults With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=123 | Terminated | Sponsor: Asceneuron S.A. | N=78 ➔ 123 | Trial completion date: Sep 2026 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Nov 2024; Strategic decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders

Drug-Drug Interaction of ASN51 With Fluvoxamine, Itraconazole and Paroxetine in Healthy Subjects (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Asceneuron S.A. | Recruiting ➔ Completed

Trial completion

Study of ASN51 in Adults With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Asceneuron S.A.

New P2 trial • Alzheimer's Disease • CNS Disorders

Asceneuron Secures $100 Million Series C Financing to Advance Groundbreaking Therapeutics in Neurodegenerative Diseases (PRNewswire) - "Asceneuron SA...today announces an $100 million oversubscribed Series C financing to advance the clinical development of its groundbreaking clinical pipeline of OGA inhibitors for the treatment of neurodegenerative diseases. The financing was led by Novo Holdings with new investment from EQT Life Sciences - LSP Dementia Fund, OrbiMed and SR One, alongside participation from existing investors M Ventures, Sofinnova Partners, GSK Equities Investments Limited and Johnson & Johnson Innovation – JJDC, Inc. The financing will be used to advance Asceneuron's lead asset ASN51 into Phase 2 clinical development for the treatment of Alzheimer's disease. ASN51 is an oral small molecule drug designed to inhibit OGA, an enzyme implicated in protein aggregation."

Financing • Alzheimer's Disease • CNS Disorders

Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51 (clinicaltrials.gov) - P1 | N=3 | Completed | Sponsor: Asceneuron S.A.

New P1 trial • Alzheimer's Disease • CNS Disorders

Drug-Drug Interaction of ASN51 With Fluvoxamine, Itraconazole and Paroxetine in Healthy Subjects (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Asceneuron S.A. | Not yet recruiting ➔ Recruiting

Enrollment open

Drug-Drug Interaction of ASN51 With Fluvoxamine, Itraconazole and Paroxetine in Healthy Subjects (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Asceneuron S.A.

New P1 trial

A Phase 1 Study demonstrating safety, CNS target engagement and PBMC pharmacodynamic response to ASN51, a novel and orally administered O-GlcNAcase inhibitor (CTAD 2023) - P1 | "ASN51 has a favorable safety profile after single and repeat dosing for up to 14 days in healthy volunteers. [18F]-IMA601 PET enzyme occupancy and PBMC O-GlcNAcylation PD results demonstrated that ASN51 achieved near-maximal and sustained CNS OGA inhibition in subjects after both single and repeated exposures. Since ASN51 target engagement is maintained following repeated dose exposure, it is suitable for use in longer duration clinical trials."

Clinical • P1 data • PK/PD data • CNS Disorders • OGA

PET Study of Repeated ASN51 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Asceneuron S.A. | Recruiting ➔ Completed

Trial completion • OGA

PET Study of Repeated ASN51 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Asceneuron S.A. | Not yet recruiting ➔ Recruiting

Enrollment open • OGA

PET Study of Repeated ASN51 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Asceneuron S.A.

New P1 trial • OGA

O-GLCNACASE INHIBITORS ASN90 AND ASN51 ARE MULTIMODAL DRUG CANDIDATE FOR AD AND PD (ADPD 2023) - "Results on ASN51-treated A53T model will be presented at the conference. Conclusions These data support the development of both ASN90 and ASN51 in tau and α-synuclein related neurodegenerative diseases, including AD and PD."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • Proteinopathy • OGA • THY1

Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of Oral ASN51 in Healthy Subjects and Subjects With Alzheimer's Disease (clinicaltrials.gov) - P1 | N=25 | Terminated | Sponsor: Asceneuron Pty Ltd. | N=76 ➔ 25 | Trial completion date: Dec 2022 ➔ Aug 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Aug 2022; Delays with sites, identifying/enrolling patients, impact of COVID, staffing, and duration

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders

Phase 1 pharmacokinetic and CNS target engagement properties of the orally administered O-GlcNAcase inhibitor ASN51 in humans (CTAD 2022) - "Altogether, the Phase 1 data suggest that daily doses of 10 mg or lower will maintain a therapeutic level of OGA inhibition with elevated O-tau and O-synuclein throughout the entire day. ASN51 thus demonstrates safety, pharmacokinetic and pharmacodynamic target engagement properties that are ideal for a once-daily, low dose CNS therapy. Based on ASN51’s optimal safety and human pharmacology profile in Phase 1, ASN51 is being advanced to a Phase 2A tau PET proof of mechanism biomarker study in early symptomatic AD patients."

Late-breaking abstract • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease • MAPT • OGA

Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of Oral ASN51 in Healthy Subjects and Subjects With Alzheimer's Disease (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Asceneuron Pty Ltd. | Trial completion date: Jan 2022 ➔ Dec 2022 | Trial primary completion date: Jan 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

[VIRTUAL] ASN51, an Orally Bioavailable Small-Molecule O-Glcnacase Inhibitor, Has Both Immediate and Disease Modifying Benefits in Preclinical Models of Parkinson’s Disease and Epilepsy (ANA 2021) - "Taken together, our data support the clin ical development of ASN51 for both disease-modifying and symptomatic indications in neurologic diseases including Parkinson’s Disease, Alzheimer’s Disease, and epilepsy. A first-in-human study of ASN51 is currently underway."

Preclinical • Alzheimer's Disease • CNS Disorders • Epilepsy • Parkinson's Disease • OGA

Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of Oral ASN51 in Healthy Subjects and Subjects With Alzheimer's Disease (clinicaltrials.gov) - P1; N=76; Recruiting; Sponsor: Asceneuron Pty Ltd.; Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders