Azafaros BV

NPC is a progressive disease where the patient has a mutation in NPC1 or NPC2 – genes that are involved in the processing of cholesterol and other lipids inside cells. Cells with this mutation have a faulty management of lipids, leading to organ damage and neurological symptoms including difficulty with speech and cognition. Delivered as an oral treatment three times per day, Miplyffa boosts the activity of two proteins in the cell called transcription factors EB (TFEB) and E3 (TFE3). These proteins upregulate genes encoding proteins that help lipids within cells to return to healthy levels. Miplyffa is specifically approved for use in combination with miglustat, a drug that is used off-label to treat NPC in around 80% of patients in the U.S. Miplyffa was approved based on results from a phase 2 trial where the drug slowed the progression of NPC compared to patients given a placebo. The company plans to launch the drug within 12 weeks of its approval and expects to set an average price of $85,000 per month for each patient, said president and CEO of Zevra Therapeutics Neil McFarlane in a public conference call ​. At the same time, Zevra launched a patient support program called AmplifyAssist to help patients and carers with personalized insurance coverage education and assistance with finding funding for their needs. “The FDA approval of Miplyffa marks a significant moment for those living with NPC and the global NPC community,” stated ​ Elizabeth Berry-Kravis, professor at Rush University Medical Center, who worked with Zevra to research Miplyffa use in a real-world setting. She added that effective NPC treatment “requires multiple treatment options due to the complexity of the disease” and that “patients will now have more access to treatments to tackle this devastating disease.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); Arimoclomol was previously developed by the Danish company Orphazyme, which rose to fame ​ in 2021 as a so-called ‘meme’ stock whose price was influenced by social media. In the same year, Orphazyme was slapped with a rejection of arimoclomol from the U.S. FDA in 2021, with the regulator requesting more data. Grappling with bankruptcy, Orphazyme sold its assets to Zevra (then known as KemPharm) in 2022 ​ for $12.8 million. Another candidate in development is IntraBio’s small molecule therapy which is being reviewed by the U.S. FDA with a decision expected in the coming days. And the Dutch company Azafaros is taking its candidate nizubaglustat into phase 3 testing in patients with a genetic diagnosis of either GM2 gangliosidosis or NPC next year ​.

LEIDEN, Netherlands--( BUSINESS WIRE )--Azafaros has announced that data from the ongoing double-blind, placebo-controlled Phase 2 RAINBOW study investigating its lead asset, nizubaglustat in patients with Niemann-Pick disease type C (NPC) or GM2 gangliosidosis, were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) annual symposium in Porto, Portugal. The results of part one of the study, designed to determine the safety, pharmacodynamics, and pharmacokinetics of the Company’s lead asset nizubaglustat, demonstrated the compound had a positive safety profile and was well-tolerated in the 13 participants in the study. All patients are now enrolled in the extension phase of the trial, where initial unblinded data on 10 patients showed 8 had improved or stabilized SARA (Scale for the Assessment and Rating of Ataxia) scores. Additionally, a reduction in seizure frequency was observed for the participants who had experienced daily seizures before recruitment into the study. Data from the RAINBOW study will be used to inform the target dose for Azafaros’ planned Phase 3 pivotal studies, due to be initiated 2025. At the conference, Azafaros also presented 12-month follow-up data from the company’s PRONTO trial, a natural history study of late-infantile/juvenile GM1 and GM2 gangliosidoses. PRONTO is the largest prospective natural history study of these two rare diseases, providing valuable insights for the further development of nizubaglustat in GM1 and GM2 and for the gangliosidoses research community in general. Stefano Portolano , MD, CEO of Azafaros, said: “ The RAINBOW trial results support the positive safety profile of nizubaglustat and provide us with encouraging early efficacy trends for the compound. We greatly appreciate the opportunity to discuss these data with the scientific community at the SSIEM annual symposium, and believe our compound offers a potential new solution to patients with rare lysosomal storage disorders with neurological involvement where there is a strong unmet medical need. We look forward to using the insights provided by results from both RAINBOW and PRONTO to keep the strong momentum of our clinical program and move the compound into pivotal trials next year .” Azafaros is thankful to the patients and their families for their participation in the RAINBOW study. Ends About the RAINBOW study The RAINBOW trial is a Phase 2 clinical study designed to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of AZ-3102 (nizubaglustat) in patients with GM2 and Niemann-Pick type C (NPC) diseases. The study was conducted across three sites in Brazil, involving 13 patients older than 12 years of age. In the first part of the study patients were randomized to receive either a high dose or low dose of nizubaglustat or placebo. All patients continued into the second part of the study where they are randomized to receive either high or low dose nizubaglustat for 52 weeks. About the PRONTO study The PRONTO study is a prospective natural history study designed to assess the progression of neurological disease in late-infantile and juvenile GM1 and GM2 gangliosidoses. The study includes participants with a late-infantile/juvenile form, genetic diagnosis, and who are between 2 and 20 years old and the main objective was to provide insight and understanding of disease progression using clinical scales, caregiver questionnaires, and actigraphy. A total of 30 participants were recruited from 6 countries with at least 12-month follow-up data on 21 participants. About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for 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. IND Clearance and Fast Track Designation for GM1/GM2 gangliosidoses and NPC 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 by scientists with a deep understanding of rare genetic disease mechanisms, using discoveries made by scientists at Leiden University and Amsterdam UMC. Azafaros is led by a team of highly experienced industry experts and aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. The Azafaros team is dedicated to rapidly bring new drugs to the rare disease patients who need them. The company is supported by a syndicate of leading investors including Forbion, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital.

Azafaros announces completion of 12-week Phase 2 RAINBOW study evaluating lead asset nizubaglustat in rare disease patients Major milestone reached in bringing new treatment options to patients and their families. Leiden, The Netherlands, March 12, 2024 – Azafaros B.V. today announced the completion of its 12-week Phase 2 clinical study, RAINBOW (Phase 2 RAINBOW studyNCT05758922). The randomized, double-blind, placebo-controlled study, conducted in Brazil, involved 13 patients from the age of 12 years who are affected by GM2 gangliosidosis or Niemann-Pick disease type C (NPC). The aim of the RAINBOW study is to determine the safety, pharmacodynamics, and pharmacokinetics of two different doses of nizubaglustat in patients, in order to identify the target dosage for Azafaros’ planned Phase 3 pivotal studies. The main part of the study is now complete, and patients are entering the extension phase, in which all of them will be given the study drug. Top line results of the RAINBOW study are expected to be announced in Q2 2024 and presented to the scientific community later this year. Prof. Dr. Roberto Giugliani, Chief of the Medical Genetics Clinical Research Group at the Hospital de Clinicas de Porto Alegre and Lead Principal Investigator for the study, said: “This is an important milestone because nizubaglustat has a dual mode of action that represents a leap forward from other agents. This dual activity targets some of the fundamental biology of the diseases with high potency and it might offer promise in pivotal studies.” Chris Freitag, Chief Medical Officer at Azafaros, said: “This is a major milestone on our journey to provide patients and their families with a potentially transformative treatment. With the RAINBOW data, we will be able to identify the optimal dose for a pediatric population in our Phase 3 efficacy study, which we plan to initiate as soon as the dose is determined, and the required approvals are in place. We are looking forward to presenting the data from RAINBOW to the scientific community. Azafaros is grateful to the patients and their families who made the decision to participate in this study.” About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for 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, a compound library from Leiden University, 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, BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital. Media ICR Consilium Amber Fennell, Ashley Tapp +44 (0)20 3709 5700 Azafaros@consilium-comms.com