Azafaros to present data from PRONTO study in patients with GM1 and GM2 gangliosidoses at the 20th annual WORLDSymposium

Leiden, The Netherlands, 23 January 2024 – Azafaros B.V. announced today it will present data from its PRONTO study in patients with GM1 and GM2 gangliosidosis at the annual WORLDSymposium™ in San  Diego, a major international research conference on lysosomal disorders. PRONTO is a landmark study and the largest prospective natural history investigation in these patients.

Out of a total of eight posters, four will focus on data from the natural history study designed to gain more  insight into these rare Lysosomal Storage Disorders. Azafaros is in the clinical stage of developing its lead  asset, nizubaglustat, as a potential treatment option for high unmet medical needs in GM1, GM2 and NPC diseases. Nizubaglustat has been shown to have an excellent tolerability profile and target engagement,  systemically, and crucially, in the central nervous system. 

As well as data from PRONTO, Azafaros will present details of its Phase 2 RAINBOW study, aimed at investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of nizubaglustat in patients with GM2 gangliosidosis or NPC. 

Details of the eight poster presentations at the WORLDSymposium™ are as follows:  

• Title: The use of wearable sensor technology to identify digital biomarkers for monitoring gait parameters in children and adolescents with GM1 and GM1 gangliosidoses. 
• Title: A natural history study of late-infantile and juvenile GM1 and GM2 gangliosidoses (PRONTO) – patients’ and caregivers’ assessments. 
• Title: A natural history study of late-infantile and juvenile GM1 and GM2 gangliosidoses  (PRONTO)- baseline clinical data. 
• Title: A natural history study of late-infantile and juvenile GM1 and GM2 gangliosidoses (PRONTO) – evaluation of different assessments. 
• Title: A Phase 2 clinical study in Niemann-Pick Type C and GM2 patients (RAINBOW).
• Title: Sleep disturbance is an important feature of neurological lysosomal disease: for patients and families. 
• Title: Swallowing disturbance is an important feature of neurological lysosomal disease – for patients and families. 
• Title: Nizubaglustat regulates GM1 ganglioside neuronal health in a human brain organoid model  of GM1 gangliosidosis. 

Additionally, Azafaros is pleased to announce that the results of the first-in-human Phase 1 study investigating the safety of nizubaglustat in healthy volunteers were also recently published in the  esteemed academic journal, Molecular Genetics and Metabolism. 

“We are very pleased to have eight posters selected for presentation at the WORLDSymposium™, the  leading congress for lysosomal diseases presenting the latest advances in basic science, translational  research and clinical trials in this area,” said Dr Christian Freitag, Chief Medical Officer at Azafaros.

“We are also thrilled that results from our first-in-human study with nizubaglustat in healthy volunteers have been published in the prestigious journal, Molecular Genetics and Metabolism. These results showed  the excellent tolerability profile of our lead compound coupled with target engagement, systemically, and  most importantly, in the central nervous system. 

“The results from PRONTO, a landmark study, have been intrinsic in informing our development plans for  nizubaglustat – including the ongoing Phase 2 RAINBOW study – and represent a significant step forward  in our quest for novel treatment options for those patients with GM1 and GM2 gangliosidoses and NPC diseases, where there is a high unmet medical need and currently very limited treatment options.” 

About nizubaglustat

Nizubaglustat is a small molecule, orally available and brain penetrant with a unique dual mode of action, with the potential to treat multiple rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses, and Niemann-Pick disease type C (NPC).

Nizubaglustat has received the following designations and support:

United States Food and Drug Administration (FDA) 

• Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC.
• Orphan Drug Designations (ODD) for GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC.
• Fast Track Designation and IND clearance for GM1 and GM2 gangliosidoses. 

European Medicines Agency (EMA) 

• Orphan Medicinal Product Designation (OMPD) for the treatment of GM2 gangliosidosis.

UK Medicines and Healthcare Products Regulatory Agency (MHRA) 

• Innovation Passport for the treatment of GM1 and GM2 gangliosidoses.

About GM1 and GM2 Gangliosidoses 

GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage  disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous  system (CNS), resulting in progressive and severe neurological impairment and early death. These diseases  mostly affect infants and children, and no disease-modifying treatments are currently available. 

About Niemann-Pick Disease Type C (NPC) 

Niemann-Pick disease type C (NPC) is a progressive, life-limiting neurological lysosomal storage disorder  caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to  the accumulation of various lipids, including gangliosides in the CNS. The onset of disease can happen  throughout the lifespan of an affected individual, from prenatal life through adulthood. 

About Azafaros 

Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease  mechanisms, compound discoveries made by scientists at Leiden University and Amsterdam UMC, and led by a team of highly experienced industry  experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment  options to patients and their families. By applying its knowledge, network and courage, the Azafaros team  challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who  need them. Azafaros is supported by a syndicate of leading Dutch and Swiss investors including Forbion,  BioGeneration Ventures (BGV), BioMed Partners, Asahi Kasei Pharma Ventures, and Schroders Capital.