Mucopolysaccharidosis III - Pipeline Insight, 2025

DelveInsight's, "Mucopolysaccharidosis III - Pipeline Insight, 2025" report provides comprehensive insights about 8+ companies and 10+ pipeline drugs in Mucopolysaccharidosis III pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered:

• Global coverage

Mucopolysaccharidosis III: Understanding

Mucopolysaccharidosis III: Overview

Mucopolysaccharidosis III, is a group of rare, autosomal recessive, neurodegenerative lysosomal storage disorders caused by deficiencies in enzymes responsible for the degradation of heparan sulfate. The syndrome is classified into four subtypes (A, B, C, and D) based on the specific enzyme deficiency, with each subtype leading to the accumulation of partially degraded heparan sulfate within lysosomes, affecting multiple organs. The clinical manifestations are characterized by severe, progressive neurodegeneration beginning in early childhood, with symptoms including cognitive decline, motor deterioration, and behavioral issues. While life expectancy is typically limited to the second or third decade, rarer, milder forms may extend survival. The incidence of Mucopolysaccharidosis III varies by subtype, with subtype A being more common in Northern Europe and subtype B in Southern Europe.

Somatic symptoms of Mucopolysaccharidosis III (MPS III) include coarse facial features with broad eyebrows, dark eyelashes, dry and rough hair, skeletal abnormalities leading to growth issues and degenerative joint disease, hepatosplenomegaly, macrocephaly, and hearing loss. However, the hallmark of the disorder is progressive degeneration of the central nervous system (CNS), which results in mental retardation and hyperactivity, typically beginning in childhood. Early development is usually normal, but between ages 1 and 3, delayed cognitive development, speech issues, and behavioral problems such as aggression may appear. As patients grow, severe behavioral disturbances like hyperactivity, sleep difficulties, and violent tendencies emerge, often peaking between ages 3 and 5. Over the next 5 to 10 years, cognitive and motor regression occurs, leading to a loss of speech, mobility, and swallowing abilities. Eventually, patients may regress to a vegetative state, with death typically occurring between the early teens and the sixth decade, depending on the disease severity.

The pathophysiology of MPS III involves the accumulation of heparan sulfate within lysosomes, which disrupts normal cellular function and leads to downstream biochemical changes, particularly in the central nervous system (CNS). This accumulation triggers secondary buildup of monosialic gangliosides GM2 and GM3 in lysosomes and other organelles, possibly due to inhibition of lysosomal enzymes or altered ganglioside trafficking. The exact role of GM2 and GM3 in neurodegeneration remains unclear, but studies suggest they contribute to neuroinflammation, exacerbating CNS damage. Heparan sulfate and ganglioside-laden neurons may activate microglia, further aggravating brain injury. Additionally, the dysfunction of lysosomal membranes, including the abnormal accumulation of cholesterol, impairs lysosomal trafficking and fusion, which in turn disrupts cellular processes like autophagy. This contributes to the accumulation of dysfunctional mitochondria, as seen in MPS III animal models, thereby intensifying cellular damage and the progressive degeneration of neuronal function.

Currently, no effective treatment halts or reverses neurodegeneration in MPS III, with management limited to palliative care. However, several approaches, including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), pharmacological chaperones, stem cell transplantation, and gene therapy, have been explored. ERT has limited success due to the blood-brain barrier, while SRT with compounds like genistein shows unclear neurological benefits. Pharmacological chaperones, such as glucosamine, stabilize mutant enzymes, and stem cell therapies aim to deliver the correct enzyme or replace damaged neurons. Gene therapy, particularly using adeno-associated viruses (AAV), has shown promising results in animal models and early clinical trials, with improvements in GAG accumulation and brain function. Challenges remain, particularly for MPS III-C due to enzyme delivery difficulties.

"Mucopolysaccharidosis III- Pipeline Insight, 2025" report by DelveInsight outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Mucopolysaccharidosis III pipeline landscape is provided which includes the disease overview and Mucopolysaccharidosis III treatment guidelines. The assessment part of the report embraces, in depth Mucopolysaccharidosis III commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Mucopolysaccharidosis III collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights:

• The companies and academics are working to assess challenges and seek opportunities that could influence Mucopolysaccharidosis III R&D. The therapies under development are focused on novel approaches to treat/improve Mucopolysaccharidosis III.

Mucopolysaccharidosis III Emerging Drugs Chapters

This segment of the Mucopolysaccharidosis III report encloses its detailed analysis of various drugs in different stages of clinical development, including Phase III, II, I, Preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

Mucopolysaccharidosis III Emerging Drugs

• UX111: Ultragenyx Pharmaceutical Inc

UX111 (rebisufligene etisparvovec) is an investigational novel in vivo gene therapy under evaluation for Mucopolysaccharidosis III type A (MPS IIIA). UX111 is designed to be dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. The therapy is designed to address the underlying sulfamidase enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. The UX111 program has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., and PRIME and Orphan Drug designations in the EU. Currently, the drug is in Preregistration stage of its development for the treatment of Mucopolysaccharidosis III.

• Trehalose: Seelos Therapeutics

Trehalose, developed by Seelos Therapeutics under the designation SLS-005, is a therapeutic agent for the treatment of Mucopolysaccharidosis III. As a low molecular weight disaccharide, trehalose is known for its ability to cross the blood-brain barrier and has been shown to activate autophagy, a crucial cellular process that helps clear misfolded proteins and cellular debris. By enhancing autophagic activity, trehalose aims to mitigate neurodegenerative effects and improve neurological function in patients with Mucopolysaccharidosis III. Trehalose has also received Orphan Drug Designation by the FDA. Currently, the drug is in Phase II stage of its clinical trial for the treatment of Mucopolysaccharidosis III.

• DNL126: Denali Therapeutics Inc.

DNL126 is an investigational enzyme replacement therapy developed for the treatment of Mucopolysaccharidosis III type A (MPS IIIA). Utilizing Denali's proprietary Enzyme Transport Vehicle (ETV) technology, DNL126 is designed to effectively cross the blood-brain barrier through receptor-mediated transcytosis, allowing for targeted delivery of SGSH to the central nervous system. By replenishing the deficient enzyme, DNL126 aims to reduce the toxic buildup of heparan sulfate in brain tissues, potentially alleviating neurological symptoms and improving overall outcomes for patients. DNL126 is a recombinant SGSH enzyme engineered to cross the blood-brain barrier, replace the SGSH enzyme and treat neuropathic and systemic forms of the Mucopolysaccharidosis III A. Currently, the drug is in Phase I/II stage of its clinical trial for the treatment of Mucopolysaccharidosis III.

Mucopolysaccharidosis III: Therapeutic Assessment

This segment of the report provides insights about the different Mucopolysaccharidosis III drugs segregated based on following parameters that define the scope of the report, such as:

• Major Players in Mucopolysaccharidosis III
• There are approx. 8+ key companies which are developing the therapies for Mucopolysaccharidosis III. The companies which have their Mucopolysaccharidosis III drug candidates in the most advanced stage, i.e. Phase III include, Ultragenyx Pharmaceutical Inc.
• Phases

DelveInsight's report covers around 10+ products under different phases of clinical development like

• Late stage products (Phase III)
• Mid-stage products (Phase II)
• Early-stage product (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates
• Route of Administration

Mucopolysaccharidosis III pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Oral
• Intravenous
• Subcutaneous
• Parenteral
• Topical
• Molecule Type

Products have been categorized under various Molecule types such as

• Recombinant fusion proteins
• Small molecule
• Monoclonal antibody
• Peptide
• Polymer
• Gene therapy
• Product Type

Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.

Mucopolysaccharidosis III: Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, II, I, preclinical and discovery stage. It also analyses Mucopolysaccharidosis III therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Mucopolysaccharidosis III drugs.

Mucopolysaccharidosis III Report Insights

• Mucopolysaccharidosis III Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Mucopolysaccharidosis III Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions:

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Mucopolysaccharidosis III drugs?
• How many Mucopolysaccharidosis III drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Mucopolysaccharidosis III?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Mucopolysaccharidosis III therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for Mucopolysaccharidosis III and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• Ultragenyx Pharmaceutical Inc
• JCR Pharmaceuticals Co., Ltd.
• GC Biopharma Corp
• Denali Therapeutics Inc.
• Orchard Therapeutics plc
• Seelos Therapeutics

Key Products

• UX111
• JR-446
• GC1130A
• DNL126
• OTL-201
• Trehalose