ezeprogind (AZP2006) / AlzProtect - LARVOL DELTA

EARLY INTERVENTION WITH AZP2006 DELAYS PROGRESSION IN PROGRESSIVE SUPRANUCLEAR PALSY: RESULTS FROM A PHASE 2A OPEN -LABEL EXTENSION (ADPD 2025) - "Early intervention with AZP2006 in PSP patients is crucial for delaying disease progression. AZP2006 has demonstrated the ability to maintain stability and slow disease progression in PSP patients."

P2a data • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

AZP2006 (Ezeprogind®): a Promising New Drug Candidate in the Battle Against Neurodegenerative Diseases. (PubMed, ChemMedChem) - "AZP2006's mechanism of action strongly suggests potential applications in other tauopathies, including Alzheimer's and Parkinson's diseases. By addressing lysosomal dysfunction and tau pathology, AZP2006 represents a promising disease-modifying approach for PSP and other neurodegenerative disorders."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: AlzProtect SAS | Trial completion date: Jul 2024 ➔ Sep 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Alzprotect Announces Supportive Results from Open-Label Extension of Phase 2a Study for Progressive Supranuclear Palsy (PSP) (Businesswire) - P2a | N=30 | NCT04008355 | Sponsor: AlzProtect SAS | "Delay in Disease Progression: During the Phase 2a trial, patients who received AZP2006 for 3 months demonstrated first signs of delay in disease progression compared to those on placebo. Stabilization in Early Disease: In the 6-month OLE phase, patients who were on the active treatment during the Phase 2a trial and initiated therapy early in their disease course exhibited remarkable stabilization of PSP during the OLE, outperforming those who were initially on placebo. Benefit in Late-Stage PSP: Notably, patients who had been on placebo during the Phase 2a trial and commenced AZP2006 treatment in the OLE phase also experienced a stabilization in their condition during the OLE. This suggests that AZP2006 may offer benefits even at advanced stages of PSP...Throughout the OLE phase, no remarkable safety concerns were observed, affirming the safety of long-term treatment with AZP2006."

P2 data • CNS Disorders • Progressive Supranuclear Palsy

Alzprotect: positive feedback from the EMA and the FDA on the phase 2b/3 development strategy in PSP [Google translation] (MyPharma Editions) - "Alzprotect announces the receipt of positive assessments from the American (FDA) and European (EMA) regulatory authorities relating to the regulatory pathway envisaged for the advancement of the clinical development of Ezeprogind/AZP2006 for the benefit of patients suffering from Progressive Supranuclear Palsy (PSP). This significant step follows the already very promising results of the phase 2a study in PSP and marks decisive progress....Regulatory authorities provided essential insights into various aspects of study design, focusing specifically on the selection of endpoints relevant to PSP and ensuring that the demographic composition and characteristics of the population of the study accurately reflect the PSP population globally."

European regulatory • FDA event • CNS Disorders • Progressive Supranuclear Palsy

First-In-Human Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of AZP2006, A Synthetic Compound for the Treatment of Alzheimer's Disease and Related Diseases. (PubMed, J Alzheimers Dis) - "AZP2006 had a favorable safety profile and was rapidly absorbed. Elevated M2 metabolite levels necessitated further studies to clarify excretion and metabolism mechanisms."

Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Progressive Supranuclear Palsy

EZEPROGIND (AZP2006) IS ABLE TO PROTECT MOTONEURONS AND NEUROMUSCULAR JUNCTIONS FROM GLUTAMATE INJURY. IN VITRO EVIDENCES (ADPD 2024) - "AZP2006 is under clinical development (Phase2a in PSP completed) and under preclinical development for the treatment of AD and related disorders, in light of our last results, AZP2006 seems to be serious candidate for ALS indication."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • Solid Tumor • TARDBP

PERFORMANCE OF A METHOD FOR QUANTIFYING PROGRANULIN AS A TARGET ENGAGEMENT BIOMARKER FOR AZP2006 IN PROGRESSIVE SUPRANUCLEAR PALSY (ADPD 2024) - "Quantification of PGRN by a method, qualified according to its context-of-use, generates robust results establishing PGRN as a target engagement biomarker for AZP2006 in PSP."

Biomarker • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Ezeprogind (azp2006), a new progranulin/prosaposin modulator, as an innovative therapeutic treatment for parkinson's disease. (Neuroscience 2023) - "Motor dysfunctions were restored after treatment at a same extend of Ambroxol (used as positive control). PGRN brain levels were increased after the treatment. Altogether, these results make of AZP2006 a serious candidate for PD treatment and synucleopathies."

CNS Disorders • Parkinson's Disease • Progressive Supranuclear Palsy • CTSD • GBA • LRRK2

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: AlzProtect SAS | Completed ➔ Active, not recruiting | Trial completion date: Jul 2022 ➔ Jul 2024

Biomarker • Enrollment closed • Trial completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Effect of AZP2006, a new treatment for Alzheimer’s Disease and Progressive Supranuclear Palsy, in the Restoration of Lysosomal Homeostasis via the Progranulin-Prosaposin Axis. (AAIC 2023) - "AZP2006 represents an original therapeutic approach to protect the PGRN-PSAP balance that is fundamental for the neuron health."

Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • Proteinopathy • Targeted Protein Degradation • CTSD

AZP2006, a New Promising Treatment for Progressive Supranuclear Palsy patients. Phase 2a Study Assessing Tolerability, Safety and Pharmacokinetics. Effect on Biomarkers and Clinical Readouts. (AAIC 2023) - P2 | "AZP2006 treatment showed promising effects after a 3-month-treatment. Considering these promising results, an open-labelled extension (OLE) was started (60 mg daily) in France. In addition, a larger Phase 2b/3 study in PSP patients testing AZP2006 efficacy over 12-month-treatment is under preparation."

Biomarker • Clinical • P2a data • PK/PD data • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

PGRN STABILISATION BY AZP2006 AS A NOVEL THERAPEUTIC STRATEGY FOR GBA1-LINKED PARKINSON'S DISEASE (ADPD 2023) - "These results highlight an exciting potential use case for AZP2006 (recently completed Phase 2a clinical development for PSP patients), in treating GBA1 -linked Parkinson's disease."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

A PHASE 2A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY ASSESSING TOLERABILITY, SAFETY, PHARMACOKINETICS OF AZP2006 IN PSP PATIENTS. BIOMARKERS INVESTIGATION. (ADPD 2023) - P2 | "Conclusions AZP2006 12-week administration was well tolerated by PSP patients and safety was overall satisfactory. In light of these encouraging results, a larger Phase 2/3 study in PSP (Europe/USA) testing its efficacy over 12 months oral treatment is under development."

Biomarker • Clinical • P2a data • PK/PD data • CNS Disorders • Immunology • Inflammation • Movement Disorders • Progressive Supranuclear Palsy

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: AlzProtect SAS | Active, not recruiting ➔ Completed

Biomarker • Trial completion • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO ASSESS TOLERABILITY, SAFETY, PHARMACOKINETICS AND EFFECT OF AZP2006 ON CEREBROSPINAL FLUID BIOMARKERS IN 36 PATIENTS WITH PROGRESSIVE SUPRANUCLEAR PALSY. (CTAD 2022) - P2 | "AZP2006C04 represents an original approach based on Progranulin modulation to treat PSP. AZP2006 12-week administration was well tolerated by patients and safety was overall satisfactory. Final validated unblinded results will be discussed."

Biomarker • Clinical • PK/PD data • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Progressive Supranuclear Palsy

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: AlzProtect SAS | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

AZP2006/EZEPROGIND neuroprotective effect in age-related cognitive decline and Alzheimer's disease progression. (PubMed, Alzheimers Dement) - "We showed that AZP2006/EZEPROGIND was able to protect neurons, enhance synaptic function, decrease the hyperphosphorylation of Tau and reduce the neuroinflammation via PGRN. The chronic oral treatment was able to prevent, protect and restore the aged-related cognitive decline in the SAMP8 mice. We postulate that neuroprotective properties of AZP2006/EZEPROGIND not only could delay the progression of AD but also has the potential to reverse aged-related cognitive damages."

Journal • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • IL1B • IL6

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2; N=36; Recruiting; Sponsor: AlzProtect SAS; Trial completion date: Jun 2021 ➔ Jun 2022; Trial primary completion date: Jun 2021 ➔ Jun 2022

Biomarker • Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

AZP2006, a new promising treatment for Alzheimer's and related diseases. (PubMed, Sci Rep) - "Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases."

Journal • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • TLR9

[VIRTUAL] AZP2006/EZEPROGIND neuroprotective effect in aged‐related cognitive decline and Alzheimer’s disease progression (AAIC 2021) - "We showed that AZP2006/EZEPROGIND was able to protect neurons, enhance synaptic function, decrease the hyperphosphorylation of Tau and reduce the neuroinflammation via PGRN. The chronic oral treatment was able to prevent, protect and restore the aged-related cognitive decline in the SAMP8 mice. We postulate that neuroprotective properties of AZP2006/EZEPROGIND not only could delay the progression of AD but also has the potential to reverse aged-related cognitive damages."

Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Movement Disorders • Progressive Supranuclear Palsy • IL1B • IL6

[VIRTUAL] NEUROPROTECTIVE EFFECTS OF EZEPROGIND® (AZP2006) IN IN VITRO AND IN VIVO MODELS OF PARKINSON’S DISEASE. (ADPD 2021) - "Altogether these results are in favor of a development of Ezeprogind in PD and synucleinopathies."

Preclinical • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

Alzprotect Strengthens Its Intellectual Property Portfolio for Its First-in-Class Clinical Stage Drug Ezeprogind (Businesswire) - "Alzprotect...announces today that the United States Patent and Trademark Office (USPTO) has recently granted patent number US 10,772,884 concerning the therapeutic uses of its first-in-class clinical stage drug Ezeprogind (AZP2006) in the treatment of tauopathies....All these patents will be in force until at least 27th December 2033, subject to patent term adjustment or extension, and similar applications are currently under examination in Canada and Brazil."

Patent • CNS Disorders • Tauopathies And Synucleinopathies

Alzprotect Forges Ahead with First Patients Enrolled in Phase 2a Study in Progressive Supranuclear Palsy (PSP) (Businesswire) - "ALZPROTECT...today announced the recruitment of the first 5 patients to participate in its phase 2a clinical trial with its drug candidate AZP2006 (named EZEPROGIND by WHO) in Progressive Supranuclear Palsy (PSP)..."

Trial status • CNS Disorders • Progressive Supranuclear Palsy

A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP (clinicaltrials.gov) - P2; N=36; Recruiting; Sponsor: AlzProtect SAS; Not yet recruiting ➔ Recruiting; Trial completion date: Dec 2020 ➔ Jun 2021; Trial primary completion date: Sep 2020 ➔ Jun 2021

Biomarker • Clinical • Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy