Allievex, a new clinical-stage biotechnology company founded by Pappas Capital, will continue the clinical program of BioMarin Pharmaceutical‘s tralesinidase alfa (formerly known as BMN 250) for the treatment of people with Sanfilippo syndrome type B.
Allievex has obtained an exclusive worldwide license for tralesinidase alfa from BioMarin, and will assume all financial obligations associated with the therapy’s development and commercialization, and manage all studies in the clinical program, which will continue uninterrupted.
“Our mission at Allievex is to develop novel therapies for children with rare pediatric neurodegenerative diseases, and we are pleased to begin executing on this mission with tralesinidase alfa,” Thomas P. Mathers, Allievex’s founder, president, and CEO, and a partner at Pappas Ventures, said in a news release.
BioMarin will provide certain manufacturing services to support a marketing authorization filing.
Allievex has completed the first round of funding co-led by Novo Holdings and Pappas Capital, and the earnings will be used to support registrational Phase 2 clinical studies of tralesinidase alfa, according to the company.
Sanfilippo syndrome type B — also known as mucopolysaccharidosis type IIIB — is an early neurodegenerative disorder caused by a deficiency in the alpha-N-acetylglucosaminidase (NAGLU) enzyme, which leads to the toxic accumulation of long complex sugar molecules called heparan sulfate.
Tralesinidase alfa is an investigational enzyme replacement therapy (ERT) designed to replace the faulty NAGLU enzyme with a healthy one in people with Sanfilippo type B. This ERT comprises a healthy version of the human NAGLU enzyme fused with a small protein derived from insulin-like growth factor 2 (IGF2), which enhances the enzyme’s ability to enter cells and do its work.
It is administered through an intracerebroventricular infusion, meaning that it is injected directly into the cerebrospinal fluid (the fluid surrounding the brain and spinal cord) of the cerebral ventricles, the four fluid-filled interconnected cavities in the brain.
This method of administration bypasses the blood-brain barrier — a protective membrane that prevents large molecules in the blood from reaching the brain — and other mechanisms that limit a therapy’s distribution in the brain, which is tralesinidase alfa’s target organ.
Preclinical studies in animal models of the disease and cells from patients have shown that tralesinidase alfa increased NAGLU activity in all brain cell types, normalized heparan sulfate levels, and reversed several disease-specific tissue changes.
Tralesinidase alfa was granted orphan drug designation by the U.S. Food and Drug Administration in 2014 and by the European Commission in 2016.
So far, the clinical program of tralesinidase alfa consists of four multicenter international studies.
The BMN 250-901 observational study (NCT02493998) evaluating the progression of Sanfilippo type B over time in 21 children up to 10 years old has been completed. The BMN 250-902 trial (NCT03227042), which is still recruiting up to 60 participants, is a natural history study of the progression of the disease over three and a half years in patients up to 18 years of age.
Data from these trials are expected to help the design and interpretation of subsequent interventional studies.
The ongoing open-label, BMN 250-201 Phase 1/2 clinical trial (NCT02754076) is evaluating the safety, tolerability, and effectiveness of tralesinidase alfa in children (up to 10 years old) with Sanfilippo type B.
In the completed Phase 1 dose-escalation part of the study, which involved three children, 300 mg of tralesinidase alfa per week was found to be the maximum tolerated dose. In the Phase 2 part of the study, these three children and up to 30 others from the BMN 250-901 observational study will receive that dose for 48 weeks while their cognitive function is assessed.
The trial’s preliminary data showed that tralesinidase alfa treatment was well-tolerated, restored the levels of heparan sulfate, halted cognitive decline, and reduced the size of the children’s liver, which is typically enlarged in people with this condition.
The open-label, BMN 250-202 Phase 2 trial (NCT03784287) is an extension study of BMN 250-201 and will evaluate the long-term safety and effectiveness of 300 mg of tralesinidase alfa given weekly over four and a half years.
“It is with confidence that we transition the development of the tralesinidase alfa program to Allievex,” said Hank Fuchs, MD, BioMarin’s president of worldwide research and development.
“We are grateful to the children and families participating in the clinical studies and will support Allievex through a smooth transition,” he added.