International Niemann–Pick Disease Alliance

Azafaros announces positive topline Phase 2 study data with nizubaglustat

Azafaros announces positive topline Phase 2 study data with nizubaglustat in
GM2 gangliosidosis and Niemann-Pick disease type C.

  • Study primary endpoint met, with confirmed safety profile
  • Investigators and Patient Organisations supportive of continued development

Leiden, The Netherlands, 19 June 2024 – Azafaros B.V. has today announced positive topline data
from its RAINBOW study, a Phase 2 clinical trial investigating nizubaglustat in patients with a genetic
diagnosis of either GM2 gangliosidosis or Niemann-Pick disease type C (NPC).

The trial was conducted across three sites in Brazil, involving 13 patients older than 12 years of age,
with the aim of determining the safety, pharmacodynamics, and pharmacokinetics of two different
doses of nizubaglustat. The results will guide the identification of the target dose for Azafaros’ planned
Phase 3 pivotal studies.

With the 12-week, double-blind and placebo-controlled part of the study complete, patients have now
entered the extension phase, in which they all receive the study drug.

Data from the RAINBOW study will be presented at the SSIEM conference in Porto in September.

Stefano Portolano, CEO at Azafaros, said: “The results of the Phase 2 RAINBOW study mark a pivotal
moment in the development of nizubaglustat. The dual mode of action sets nizubaglustat apart as a
leap forward from other agents. We are reassured by the results of the study and more than confident
that nizubaglustat has the potential to become a convenient, life-changing therapy for patients
affected by GM1 and GM2 gangliosidoses and NPC. Azafaros is thankful to the patients and their
families for their important contribution to the RAINBOW study. Azafaros is now poised to embark on
the global Phase 3 trial next year.

Lead RAINBOW investigator, Roberto Giugliani, added: “We are pleased to report the completion of
this important step in the development of a new therapy for GM2 gangliosidosis and Niemann-Pick
disease type C, which delivers data to determine the best dosing of nizubaglustat and allows the
planning of the next phase.

In a statement, a representative from the Associação Niemann-Pick & Batten Brasil (ANPB), a patient
organisation in Brazil, said there was an urgent need for new treatments for NPC.

Current therapeutic options are limited and do not offer a definitive cure,” the statement read.
Clinical research plays a crucial role in this process, allowing the development and evaluation of new
therapies that can improve patients’ quality of life and slow the progression of the disease.
Therefore, we are excited about developing innovative and convenient therapies.

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 Dutch and Swiss investors including Forbion,
BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital.

For further information:
Azafaros B.V.
Email: info@azafaros.com
www.azafaros.com

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