Sanfilippo Syndrome- Pipeline Insight, 2025

This “Sanfilippo Syndrome - Pipeline Insight, 2025” report provides comprehensive insights about 8+ companies and 10+ pipeline drugs in Sanfilippo Syndrome 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.

Sanfilippo Syndrome: Understanding

Sanfilippo Syndrome: Overview

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS 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 Sanfilippo syndrome varies by subtype, with subtype A being more common in Northern Europe and subtype B in Southern Europe.

Somatic symptoms of Sanfilippo syndrome (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 Sanfilippo syndrome (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 Sanfilippo syndrome (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.

'Sanfilippo Syndrome- Pipeline Insight, 2025' report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Sanfilippo Syndrome pipeline landscape is provided which includes the disease overview and Sanfilippo Syndrome treatment guidelines. The assessment part of the report embraces, in depth Sanfilippo Syndrome 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, Sanfilippo Syndrome 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 Sanfilippo Syndrome R&D. The therapies under development are focused on novel approaches to treat/improve Sanfilippo Syndrome.

Sanfilippo Syndrome Emerging Drugs Chapters

This segment of the Sanfilippo Syndrome 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.

Sanfilippo Syndrome Emerging Drugs

UX111: Ultragenyx Pharmaceutical Inc

UX111 (rebisufligene etisparvovec) is an investigational novel in vivo gene therapy under evaluation for Sanfilippo syndrome 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. In December 2024, Ultragenyx Pharmaceutical announced the submission of a Biologics License Application to the US Food and Drug Administration seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A.

OTL-201: Orchard Therapeutics

OTL-201 is an ex vivo autologous gene therapy being developed for the treatment of Sanfilippo syndrome. It uses a modified virus to insert a functional copy of the SGSH gene into a patient’s cells. OTL-201 has received rare pediatric disease designation from the FDA and is currently being evaluated in an ongoing proof-of-concept clinical trial. OTL-201 is an investigational therapy and has not been approved by any regulatory agency or health authority.

DNL126: Denali Therapeutics Inc.

DNL126 is an investigational enzyme replacement therapy developed for the treatment of Sanfilippo Syndrome 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 Sanfilippo syndrome A. Currently, the drug is in Phase I/II stage of its clinical trial for the treatment of Sanfilippo Syndrome.

Sanfilippo Syndrome: Therapeutic Assessment

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

Major Players in Sanfilippo Syndrome

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

Phases

The 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

Sanfilippo Syndrome 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.

Sanfilippo Syndrome: Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, II, I, preclinical and discovery stage. It also analyses Sanfilippo Syndrome 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 Sanfilippo Syndrome drugs.

Sanfilippo Syndrome Report Insights

• Sanfilippo Syndrome Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Sanfilippo Syndrome 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 Sanfilippo Syndrome drugs?
• How many Sanfilippo Syndrome drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Sanfilippo Syndrome?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Sanfilippo Syndrome 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 Sanfilippo Syndrome 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

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