Polaryx Therapeutics Advances Phase 2 Trial for Rare Pediatric Lysosomal Storage Disorders

Polaryx Therapeutics, Inc. (NASDAQ:PLYX) announced it has selected a contract research organization (CRO) to conduct SOTERIA, a phase 2 trial evaluating its lead candidate PLX-200 across four rare lysosomal storage disorders (LSDs). The open-label, single-arm trial will assess PLX-200's safety, tolerability, and clinical activity in patients with CLN2, CLN3, Krabbe disease, and Sandhoff disease.

"Our selection of a CRO partner marks an important milestone for us as we continue to advance the clinical development of SOTERIA and move closer to the clinic," said the Chief Medical Officer in a press release statement. The company received a safe-to-proceed letter from the FDA in October 2025 and plans to initiate the trial in the first half of 2026 at sites in the United States, Europe, and potentially Asia.

The conditions targeted by the SOTERIA trial represent approximately one quarter of the LSD population. LSDs are a heterogeneous group of more than 50 inherited rare metabolic diseases caused by mutations in genes encoding lysosomal enzymes or associated proteins. These mutations result in the accumulation of undegraded substrates within lysosomes, leading to cellular dysfunction, chronic inflammation, and cell apoptosis. LSDs often manifest in infancy or early childhood and are associated with severe clinical outcomes, including developmental regression, seizures, blindness, motor impairment, and premature death. LSDs affect approximately 1 in 5,000 births.

CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis, is associated with mutations in the CLN2 gene, which encodes lysosomal tripeptidyl-tripeptidase I. This mutation results in a deficiency and/or loss of function of the TPP1 protein that leads to intralysosomal accumulation of auto-fluorescent lipopigments known as ceroid-lipofuscin. Globally, the classical form of CLN2 disease has a prevalence of 0.6 to 0.7 per million inhabitants.

CLN3 disease, also known as juvenile neuronal ceroid lipofuscinosis or juvenile Batten disease, is a rare inherited LSD that primarily affects the nervous system in childhood. With a prevalence of one in 100,000 births worldwide, CLN3 disease is caused by mutations in the CLN3 gene which encodes a lysosomal transmembrane protein, Battenin. Due to impaired lysosomal function, neurons accumulate waste material and progressively deteriorate, resulting in a neurodegenerative disease course.

Krabbe disease, also known as globoid cell leukodystrophy, is caused by mutations in the galactosylceramidase gene, leading to galactocerebrosidase deficiency and an inability to break down certain lipids in the body. This results in accumulation of toxic substances in the brain and other areas of the nervous system leading to demyelination and severe neurological decline. The incidence rate of Krabbe disease varies significantly, affecting 0.3 to 2.6 per 100,000 live births. Hematopoietic stem cell transplantation is considered the current standard of care.

Sandhoff disease is part of a group of inherited disorders called GM2 gangliosidoses, resulting from deficiencies in the hexosaminidase enzyme. This mutation leads to an accumulation of GM2 ganglioside in nerve cells, resulting in rapid neurodegeneration. Sandhoff Disease has a prevalence of approximately 0.67 per 100,000 births. There is currently no established standard of care for these diseases.

PLX-200 is an orally available compound comprised of gemfibrozil, an FDA-approved lipid regulating agent. According to the company, gemfibrozil's ability to cross the blood-brain barrier has been documented in preclinical trials. The company presented preclinical data at the 22nd Annual WORLDSymposium in San Diego. According to the press release, PLX-200 showed positive effects in a mouse model of Krabbe disease. The data revealed that the orally administered gemfibrozil reduced astrogliosis and neuroinflammation. It also protected myelin and decreased the accumulation of psychosine, a toxic metabolite linked to Krabbe disease, in the tested mouse models.

The SOTERIA trial design includes flexibility to compare treatment results against natural history data for the CLN2 and CLN3 cohorts. The company indicated that compelling clinical activity could potentially lead to seeking conditional marketing authorization.

Polaryx Therapeutics is a clinical-stage biotechnology company developing novel, disease-modifying therapies for rare, pediatric lysosomal storage disorders. The company completed its initial public offering earlier this year. The National Organization for Rare Diseases notes that a disease is considered rare when it affects fewer than 1 in 2,000 people globally, with approximately 70% of these diseases starting in childhood. There are more than 6,000 rare diseases identified, 72% of which are genetically inherited. More than 300 million people worldwide live with rare diseases, representing about 3.5% to 5.9% of the global population.