What is Azafaros?
Azafaros is a Netherlands-based clinical-stage biotech company founded in 2018 that focuses on developing disease-modifying, oral small molecule therapeutics for patients with severe rare genetic lysosomal storage disorders affecting the central nervous system. Headquartered in Leiden with operations in Switzerland, the company raised an oversubscribed €132 million Series B financing round in May 2025, one of the largest European rare disease biotech fundraises of the year.
The company’s lead candidate, nizubaglustat, represents decades of research from Leiden University and Amsterdam University Medical Center. This orally available, brain-penetrant drug entered global Phase 3 pivotal trials in late 2025 for Niemann-Pick disease Type C and GM1/GM2 gangliosidoses, conditions that predominantly affect infants and children, causing progressive neurodegeneration with often fatal outcomes. Currently, no disease-modifying treatments exist for these devastating conditions.
The Diseases: Understanding Fatal Childhood Neurological Disorders
Niemann-Pick Disease Type C
Niemann-Pick disease Type C (NPC) is a progressive, life-limiting neurological lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes. These genetic defects lead to aberrant endosomal-lysosomal trafficking, causing various lipids, including gangliosides, to accumulate in the brain and other organs.
Children with NPC typically appear healthy at birth but develop symptoms in early childhood. Initial signs often include clumsiness, difficulty walking, and problems with eye movements. As the disease progresses, affected children experience seizures, intellectual disability, loss of previously acquired skills, difficulty swallowing, and progressive dementia. Most children with the late-infantile form, which represents the majority of cases, survive only into their teenage years.
The condition affects approximately 1 in 100,000 to 150,000 live births globally. Whilst rare, the devastating impact on families and the absence of effective treatments create enormous medical need and emotional toll. Parents watch helplessly as their children lose abilities, knowing current medicine offers only palliative care.
GM1 and GM2 Gangliosidoses
GM1 gangliosidosis and GM2 gangliosidoses, which include Tay-Sachs disease and Sandhoff disease, are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides in the central nervous system. These complex lipids build up because enzyme deficiencies prevent their normal breakdown in cells’ lysosomes, the cellular compartments responsible for recycling biomolecules.
The infantile forms of these conditions are particularly tragic. Babies typically appear normal for the first few months of life before developmental delays become apparent around 3 to 6 months of age. Affected infants lose motor skills, develop seizures, become blind and deaf, and experience progressive paralysis. Most children with infantile GM1 or GM2 gangliosidosis die by age 3 to 5 years.
Juvenile-onset forms present later in childhood with slower progression but similarly devastating outcomes. Children develop problems with movement and balance, experience progressive intellectual decline, and ultimately lose all independence. Like NPC, these conditions have no approved disease-modifying treatments. Current care focuses solely on managing symptoms and providing comfort.
Revolutionary Science: How Nizubaglustat Works
The Drug’s Unique Dual Mechanism
Nizubaglustat is a small molecule, orally available azasugar with a unique dual mode of action addressing lipid accumulation through two complementary pathways. This dual approach distinguishes nizubaglustat from most therapies for lysosomal storage disorders, which typically target only the missing enzyme.
The drug works as a brain-penetrant inhibitor of two enzymes in glycosphingolipid metabolism: ceramide glucosyltransferase and non-lysosomal neutral glucosylceramidase (NLGase). By inhibiting ceramide glucosyltransferase, nizubaglustat reduces the production of glucosylceramide, the precursor to gangliosides and other complex lipids that accumulate in disease. By inhibiting NLGase, the drug promotes alternative lysosomal pathways for lipid degradation that remain functional even when primary enzymes are deficient.
This dual mechanism maintains the balance of complex membrane lipids regardless of which specific enzyme is deficient due to genetic mutations. The approach enables nizubaglustat to potentially treat multiple lysosomal storage disorders with different underlying genetic causes, a major advantage over enzyme replacement therapies specific to single conditions.
Brain Penetration: Overcoming the Blood-Brain Barrier
One of nizubaglustat’s most critical properties is its ability to cross the blood-brain barrier, the protective membrane that prevents most substances from reaching brain tissue. This barrier protects the brain from toxins but also blocks most drugs, creating enormous challenges for treating neurological conditions.
Nizubaglustat’s small molecular size and chemical properties enable it to pass through the blood-brain barrier effectively, reaching the brain tissues where lipid accumulation causes damage. This brain penetration proves essential because NPC and gangliosidoses primarily affect the nervous system. Treatments that cannot reach the brain offer little benefit regardless of their effects elsewhere in the body.
The drug’s oral availability represents another crucial advantage. Patients take nizubaglustat as a daily pill rather than requiring intravenous infusions in hospitals. For families already burdened by caring for severely ill children, this convenience reduces treatment burden whilst maintaining consistent drug levels that continuous oral dosing provides.
From Academic Discovery to Clinical Candidate
Nizubaglustat emerged from decades of research by teams led by Professors Hermen Overkleeft, Stan van Boeckel, and Hans Aerts at Leiden University. Professor Aerts, a pioneer in glycosphingolipid metabolism research, developed fundamental understanding of how these complex lipids function in health and disease.
The Leiden researchers designed azasugars, sugar-like molecules that can inhibit enzymes involved in glycosphingolipid metabolism. Through systematic medicinal chemistry, they optimised these molecules for potency, selectivity, brain penetration, and safety. The work spanned years of laboratory research, animal testing, and iterative refinement before producing nizubaglustat as a clinical candidate.
Professor Overkleeft reflects on the journey: “It is really rewarding to see the results of decades of research between my lab and that of Hans progress to this stage. I sincerely hope the company will succeed in its programme to get registration of this new drug so that these devastating diseases for which currently no satisfying solutions exist can be treated.”
Clinical Development: From Laboratory to Late-Stage Trials
Phase 2 Results: Promising Early Data
Earlier in 2025, the company reported positive topline results from its ongoing Phase 2 study evaluating nizubaglustat in patients with GM2 gangliosidosis and NPC. The extension study demonstrated a favourable safety profile after more than 12 months of treatment, addressing a primary concern for any novel therapy.
More encouragingly, preliminary improvements or stabilisation in key clinical endpoints were observed in the majority of patients. For progressive, invariably fatal conditions, stabilisation represents meaningful benefit. Slowing or halting disease progression could provide affected children with months or years of additional quality life whilst researchers work toward more complete treatments.
The Phase 2 data provided sufficient confidence for the company and its investors to commit to Phase 3 pivotal trials, the final and most expensive stage of clinical development. Positive Phase 2 results don’t guarantee Phase 3 success, but they substantially reduce risk and demonstrate proof-of-concept that the drug’s mechanism translates to clinical benefit.
Phase 3 NAVIGATE Studies: The Pivotal Trials
In late 2025, the company initiated two global Phase 3 studies, collectively called the NAVIGATE programme, targeting late-infantile and juvenile-onset forms of NPC and GM1/GM2 gangliosidoses. The first patient was dosed in the pivotal, multicentre clinical programme, marking a significant milestone for the company and families affected by these conditions.
The Phase 3 programme aims to assess nizubaglustat’s potential to alter disease progression and improve functional outcomes in these patient populations. The studies will recruit approximately 70 patients in each indication across 35 centres globally. This extensive network ensures sufficient patient enrollment whilst enabling families to access trials relatively near their homes rather than travelling to distant centres.
The trials are projected to take 18 months, with primary endpoints focused on slowing functional decline measured through standardised neurological assessments. Secondary endpoints will evaluate safety, tolerability, quality of life, and biomarkers indicating drug mechanism of action. Regulatory authorities including the FDA and EMA will review this data to determine whether to approve nizubaglustat for commercial use.
If successful, introduction to the market could occur by the end of 2028, representing an unusually rapid timeline from Phase 3 initiation to potential approval. The timeline reflects both regulatory designations enabling accelerated review and the severe unmet need motivating expedited development.
Record €132 Million Funding: Building a Rare Disease Leader
The Series B Round Details
In May 2025, the company completed an oversubscribed €132 million Series B financing, one of the largest European rare disease biotech rounds of the year. The round was led by Jeito Capital and co-led by Forbion Growth, with participation from Seroba, Pictet Group, and existing investors including Forbion Ventures, Schroders Capital, and BioGeneration Ventures.
The oversubscribed nature proved particularly significant. Multiple additional investors sought to participate but were unable to secure allocations, reflecting strong demand from the life sciences investment community. This investor enthusiasm validated both the scientific rationale and commercial opportunity whilst ensuring the company received favourable terms.
Three new board members joined from the investor group: Rachel Mears and Julien Elric from Jeito Capital, and Audrey Cacaly from Forbion Growth. These experienced rare disease investors bring operational expertise, strategic guidance, and connections to pharmaceutical companies potentially interested in partnerships or acquisition.
What the Funding Enables
The €132 million provides runway to complete both Phase 3 studies and prepare for potential commercial launch. Specific uses include patient recruitment across 35 global centres, ongoing clinical trial operations over 18 months, regulatory filings with FDA, EMA, and other agencies, commercial manufacturing scale-up, market access and reimbursement preparations, and pipeline expansion to additional lysosomal storage disorders.
The company emphasised that funding will also support expanding its pipeline beyond nizubaglustat to other indications. Whilst details remain undisclosed, the scientific understanding and technical capabilities developed through nizubaglustat position the company to address additional rare diseases using similar approaches.
Previous Funding History
The company was founded in 2018 by BioGeneration Ventures partnering with Leiden Libertatis Ergo Holding, Leiden University’s technology transfer office. Initial seed funding came from BGV and the university, supporting early preclinical development and IND-enabling studies.
In 2020, the company raised a €25 million Series A led by Forbion Ventures with participation from Schroders Capital and BGV. This financing enabled Phase 1 and Phase 2 clinical trials demonstrating safety and preliminary efficacy that de-risked the asset before the much larger Series B.
Total funding now exceeds €160 million, substantial capitalization for a clinical-stage rare disease company. This financial strength ensures the company can complete development without needing additional financing during critical Phase 3 trials, avoiding potential delays or dilution at inopportune times.
Leadership: A Seasoned Rare Disease Team
Stefano Portolano: Chief Executive Officer
Stefano Portolano serves as CEO, bringing extensive rare disease drug development and commercialisation experience. His background spans roles at major pharmaceutical companies and biotech startups, providing the operational expertise and industry relationships essential for successfully bringing rare disease drugs to market.
Portolano emphasises the mission driving the company: “This successful Series B round marks a significant milestone, allowing us to accelerate the development of nizubaglustat and leverage our scientific understanding and competencies to bring additional candidates into development. The fact that we have been able to attract leading life sciences investors to join our existing, strong group of specialist investors is a testament to the impressive accomplishments of the team and the large unmet medical need that currently exists for patients with these hugely debilitating neurological diseases. We look forward to bringing nizubaglustat to patients.”
His leadership focuses on execution excellence, ensuring clinical trials enroll efficiently, regulatory strategies maximize approval probability, and commercial preparations position nizubaglustat for successful launch if trials succeed.
The Scientific Advisory Board
The company’s Scientific Advisory Board includes world-leading specialists in lysosomal storage disorders, clinical neurology, and rare disease drug development. These advisers guide trial design, help interpret clinical data, connect the company with key opinion leaders who influence treatment decisions, and provide credibility with regulators and investors.
The involvement of Professors Overkleeft and Aerts, the drug’s inventors, ensures continuity between academic discovery and clinical development. Their deep mechanistic understanding proves invaluable when interpreting clinical results or troubleshooting unexpected findings.
Regulatory Designations: Accelerated Pathways to Patients
Nizubaglustat has received an impressive array of regulatory designations recognizing both the severe unmet need and the drug’s potential to address it.
Orphan Drug Designation (US and Europe): Granted for GM1 gangliosidosis, GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), and NPC. This designation provides seven years of market exclusivity in the US and ten years in Europe, along with protocol assistance, fee waivers, and tax incentives.
Rare Pediatric Disease Designation (US): Granted for all three conditions. If nizubaglustat is approved, the company will receive a Priority Review Voucher that can be used to obtain expedited FDA review of another drug or sold to other companies, often for $100 million or more.
Fast Track Designation (US): Enables more frequent FDA interactions, rolling review of clinical trial data, and potential for accelerated approval based on surrogate endpoints rather than requiring full demonstration of clinical benefit.
Orphan Medicinal Product Designation (Europe): Granted by the European Medicines Agency for GM1 and GM2 gangliosidoses.
Innovation Passport (UK): Granted by the UK MHRA for GM1 and GM2 gangliosidoses, enabling access to the Innovative Licensing and Access Pathway designed to accelerate time to patients for promising new medicines.
These designations reflect consensus amongst global regulators that nizubaglustat addresses critical unmet need and merits expedited development and review.
Frequently Asked Questions About Azafaros
What diseases does nizubaglustat treat?
Nizubaglustat is being developed for Niemann-Pick disease Type C (NPC) and GM1/GM2 gangliosidoses, which include Tay-Sachs disease and Sandhoff disease. These are fatal rare genetic conditions primarily affecting children, causing progressive brain damage due to lipid accumulation. Currently, no disease-modifying treatments exist for these conditions.
How does nizubaglustat work differently from other treatments?
Nizubaglustat has a unique dual mechanism of action. It inhibits two enzymes involved in glycosphingolipid metabolism, both reducing production of harmful lipids and promoting their degradation through alternative pathways. This approach works regardless of which specific enzyme is genetically deficient, potentially enabling one drug to treat multiple conditions. The drug also crosses the blood-brain barrier, reaching affected tissues.
When could nizubaglustat be available to patients?
Phase 3 clinical trials began in late 2025 with results expected in 18 months. If trials are successful, regulatory submissions would follow immediately. Given the multiple expedited regulatory designations and severe unmet need, approval could potentially occur by the end of 2028. However, clinical trial success is never guaranteed, and timelines depend on trial outcomes and regulatory review.
Where is the company based and who leads it?
The company is headquartered in Leiden, Netherlands, with operations in Switzerland. CEO Stefano Portolano leads a seasoned team of rare disease drug development professionals. The company was founded in 2018 by BioGeneration Ventures based on decades of research from Leiden University and Amsterdam University Medical Center.
How much funding has the company raised?
In May 2025, the company raised an oversubscribed €132 million Series B led by Jeito Capital and co-led by Forbion Growth. Previous funding included a €25 million Series A in 2020. Total capital raised exceeds €160 million, providing resources to complete Phase 3 trials and prepare for commercial launch if trials succeed.
Will nizubaglustat be expensive?
Pricing has not been announced, as the drug is still in clinical trials. Rare disease drugs typically carry high prices reflecting small patient populations, development costs, and value to patients. However, regulatory designations and potential Priority Review Vouchers provide economic incentives. Many countries have special funding mechanisms for rare disease treatments ensuring patient access regardless of cost.