NPC1

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

The new Prescription Drug User Fee Act (PDUFA) action date set by the FDA is September 21, 2024 March 04, 2024 -- Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra or the Company), a rare disease therapeutics company, today announced the U.S. Food and Drug Administration (FDA) has extended the review period for the New Drug Application (NDA) for arimoclomol, an investigational orally delivered, first-in-class treatment for Niemann-Pick disease type C (NPC). In addition, the FDA has set a new Prescription Drug User Fee Act (“PDUFA”) action date of September 21, 2024, and has re-affirmed its intent to present the resubmission for discussion at an advisory committee meeting to be scheduled. As previously reported, Zevra received acceptance of the NDA resubmission for arimoclomol in early January 2024, with an original PDUFA action date of June 21, 2024. The arimoclomol NDA resubmission included evidence supporting trial metrics, FDA-preferred analyses, and data from a multitude of additional studies that provide supportive evidence of arimoclomol’s impact in clinical and nonclinical settings. As part of the ongoing review, Zevra received notification from the FDA that it required more time to review the additional analyses provided by the Company in responses to recent information requests generated from the FDA’s review. The FDA has determined that the additional information constitutes a Major Amendment to the NDA, thereby resulting in an extension of the PDUFA action date.“While the PDUFA action date extension represents a delay, we remain confident in the potential for arimoclomol to help people living with NPC, and we will continue to work closely with the FDA as they complete their review,” said Neil F. McFarlane, President and Chief Executive Officer of Zevra. “We applaud the NPC Patient Advocacy Community who recently submitted an informal petition to the FDA in support of arimoclomol and reinforcing the urgent need for an FDA-approved treatment to improve the course of this relentless and fatal disease. As the review continues, Zevra will maintain the early access program for arimoclomol and work tirelessly to bring this potential therapy to patients as soon as possible.” Niemann-Pick disease type C (NPC) is an ultra-rare, progressive, and neurodegenerative lysosomal storage disorder characterized by an inability of the body to transport cholesterol and other lipids within the cell, leading to an accumulation of these substances in various tissue areas, including brain tissue. The disease is caused by mutations in the NPC1 or NPC2 genes, which are responsible for making lysosomal proteins. Both children and adults can be affected by NPC with varying clinical presentations. Those living with NPC lose independence due to physical and cognitive limitations, with key neurological impairments presenting in speech, cognition, swallowing, ambulation, and fine motor skills. Disease progression is irreversible and can be fatal within months or take years to be diagnosed and advance in severity. Arimoclomol, Zevra’s orally delivered, first-in-class investigational product candidate for the treatment of NPC, has been granted Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, and Rare Pediatric Disease designation by the FDA, and Orphan Medicinal Product designation for the treatment of NPC by the European Medicines Agency (EMA). The FDA has accepted the resubmission of the NDA for arimoclomol and has set a user fee goal date (PDUFA date) of September 21, 2024. Zevra Therapeutics is a rare disease company combining science, data, and patient needs to create transformational therapies for diseases with limited or no treatment options. Our mission is to bring life-changing therapeutics to people living with rare diseases. With unique, data-driven development and commercialization strategies, the Company is overcoming complex drug development challenges to make new therapies available to the rare disease community. Expanded access programs are made available by Zevra Therapeutics and its affiliates and are subject to the Company's Expanded Access Program (EAP) policy as published on its website at www.zevra.com. Participation in these programs is subject to the laws and regulations of each jurisdiction under which each respective program is operated. Eligibility for participation in any such program is at the treating physician's discretion. The content above comes from the network. if any infringement, please contact us to modify.

Azafaros to present data from PRONTO study in patients with GM1 and GM2 gangliosidoses at the 20th annual WORLDSymposium™ Four posters with baseline data from the natural history (PRONTO) study in patients with GM1 and GM2 gangliosidoses to be presentedTotal of eight posters from Azafaros, including study design for the Phase 2 RAINBOW study investigating the company’s lead product, nizubaglustat, in patients with GM2 gangliosidosis and Niemann-Pick disease type C (NPC) selected for presentationSeparately, the results of the Phase 1 first-in-human study, testing the safety of nizubaglustat in healthy volunteers, was recently published in the leading peer-reviewed journal, Molecular Genetics and Metabolism 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 20th annual WORLDSymposium™ in San Diego from 4-9 February, 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 nizubaglustatNizubaglustat 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 GangliosidosesGM1 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 AzafarosAzafaros 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 (BGV), BioMed Partners, Asahi Kasei Pharma Ventures, and Schroders Capital. For further information: Azafaros B.V. Email: info@azafaros.com www.azafaros.com