Our Therapeutic Approach
A small molecule with the potential to become the first disease-modifying therapy for GM1 and GM2 gangliosidoses and Niemann-Pick disease type C
In recent years, researchers have discovered several enzymes that may serve as potential targets for the treatment of neurodegenerative lysosomal storage disorders.
Our lead candidate, nizubaglustat, was discovered by a group of scientists in the Netherlands (read more on Our Story and Mission) and belongs to the drug class of small molecules. With their ability to pass through cell membranes and the blood-brain barrier, these small molecules offer the opportunity to reach intracellular targets, including in the brain and spinal cord (central nervous system).
Nizubaglustat is designed to reach the central nervous system and to change the metabolism of certain fats or lipids. Through this mechanism, nizubaglustat has the potential to reduce the harmful accumulation of “waste” lipids and to reduce the impact of the impaired lysosome on cell function. Our initial goal with nizubaglustat is to develop a disease-modifying therapy for GM1 and GM2 gangliosidoses and Niemann-Pick disease type C to improve the lives of these patients.
Nizubaglustat can be swallowed in tablet form and therefore offers the possibility of convenient administration and treatment at home, which would significantly preserve the life quality of patients and their families. Nizubaglustat has the potential to provide the first disease-modifying therapy that that can be effective regardless of whether the patient is afflicted by GM1/ GM2 gangliosidoses, or NPC.
An essential stage of all drug development is human trials
Our Phase I first-in-human Study with AZ-3102 (now nizubaglustat)
Our Phase I Study in healthy volunteers assessed the safety and tolerability of nizubaglustat, with specific measurements on drug levels and biomarkers in plasma and cerebrospinal fluid (CSF). The study design served the future development of nizubaglustat in neurological lysosomal storage disorders, including GM1 and GM2 gangliosidoses, and Niemann-Pick disease type C
Our Natural History Study: PRONTO
This is a prospective longitudinal study of neurological disease trajectory in children living with late-infantile or juvenile onset of GM1 or GM2 gangliosidoses.
It was designed by our clinical team to gain more insight in the natural development of the disease, with this prospective Natural History Study named PRONTO (PROspective Neurological Disease TrajectOry Study).
By enrolling children with late infantile and juvenile onset of GM1 and GM2 gangliosidoses, we aim to understand how the disease progresses, with a focus on how it affects neurological signs and symptoms, and to identify if some patients have different traits that could explain and predict how their disease will progress.
In this way, we can build an external control dataset and develop a model of disease progression. This study will support the future development of a clinical trial investigating the potential of our lead therapeutic candidate, nizubaglustat, in this patient group.
PRONTO is an ongoing multinational study being conducted in 6 countries, with 31 participants between the ages of 2 and 20 years enrolled. All participants had neurological disease onset after their 1st birthday. Enrolment was initiated in 2021 and follow-ups with participants will continue until September 2025. The enrolment is now closed.
We are grateful to the families and the patients for their commitment and support in the gathering of this important data which will be highly valuable for the development of future treatments.
Click here for the published clinical trial information: www.clinicaltrials.gov.
For any questions and specific information on our PRONTO study, please send an email to pronto@azafaros.com
Our Phase II Study: RAINBOW
A RAndomised, double-blINd, placeBo-controlled, multicenter, 12-week study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Oral nizubaglustat in patients With GM2 gangliosidosis or Niemann-Pick disease type C (NPC).
The aim of this study was to assess the correct doses of nizubaglustat to treat GM2 and NPC diseases by evaluating the clearance of nizubaglustat from the body and the effect of two different doses in a small number of patients with those diseases.
RAINBOW was designed as a short, multinational study, with 12 participants (six per disease) between the ages of 12 and 20 years, with late-infantile or juvenile onsets. Enrolment commenced in early 2023 and there was a duration study time of three months per patient. This study has now been completed. For more information, please send an email to info@azafaros.com.