adrabetadex (VTS-270) / Mandos Health - LARVOL DELTA

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2024 ➔ Oct 2025 | Trial primary completion date: Jun 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders

Elevated Cerebrospinal Fluid Total Tau in Niemann-Pick Disease Type C1: Correlation With Clinical Severity and Response to Therapeutic Interventions. (PubMed, J Inherit Metab Dis) - "Baseline CSF total Tau levels were decreased 40% (p = 0.0066) in individuals being treated with miglustat, and longitudinal analysis substantiated this observation with a 40% decrease (p < 0.0001, 95% CI 32%-47.4%). Longitudinal analysis also showed a significant (p = 0.004) decrease of 19% (95% CI 7%-30%) in total Tau levels associated with intrathecal 2-hydroxypropyl-β-cyclodextrin therapy. These data show that CSF total Tau levels are significantly increased in individuals with NPC1, positively correlated with increased disease severity, and respond to therapeutic interventions."

Biomarker • Journal • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases • CSF T-tau

Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System (clinicaltrials.gov) - P3 | N=27 | Terminated | Sponsor: Mandos LLC | Completed ➔ Terminated; Sponsor had determined that the benefit-risk profile of adrabetadex was not favorable and the clinical development program for adrabetadex was discontinued.

Trial termination • Genetic Disorders • Lysosomal Storage Diseases

Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1 (clinicaltrials.gov) - P2/3 | N=2 | Terminated | Sponsor: Mandos LLC | Phase classification: P2b ➔ P2/3

Phase classification • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Recruiting

Enrollment open • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2 | N=3 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders • NPC1

Low Risk Profile of Long-Term Repeated Lumbar Puncture for Intrathecal Delivery of 2-Hydroxypropyl-Beta-Cyclodextrin in Patients With Niemann-Pick Type C. (PubMed, Pediatr Neurol) - "This study shows that frequent repeated LPs are possible for delivery of intrathecal therapy and can be accomplished with a very low rate of post-LP adverse events."

Journal • Anesthesia • Back Pain • Musculoskeletal Pain • Pain

VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease (clinicaltrials.gov) - P2b | N=56 | Completed | Sponsor: Mandos LLC | Active, not recruiting ➔ Completed

Trial completion • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • NPC1

Neurofilament Light Chain in Cerebrospinal Fluid as a Novel Biomarker in Evaluating Both Clinical Severity and Therapeutic Response in Niemann-Pick Disease, Type C1. (PubMed, Genet Med) - "CSF NfL levels are increased in individuals with NPC1, are associated with clinical disease severity and are decreased with miglustat therapy. These data suggest that NfL is a biomarker that may have utility in future therapeutic trials."

Biomarker • Journal • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • CSF NfL • NEFL

Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1 (clinicaltrials.gov) - P1/2 | N=2 | Terminated | Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Completed ➔ Terminated; Enrollment was poor due to COVID-19 pandemic

Trial termination • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • NPC1

Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1 (clinicaltrials.gov) - P2b | N=2 | Terminated | Sponsor: Mandos LLC | Active, not recruiting ➔ Terminated; Terminated by previous Sponsor decision

Trial termination • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Adrabetadex to Treat Niemann-Pick Type C1 (NPC1) Disease (clinicaltrials.gov) - P2b | N=66 | Terminated | Sponsor: Mandos LLC | Active, not recruiting ➔ Terminated; Terminated by previous Sponsor decision

Trial termination • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System (clinicaltrials.gov) - P3 | N=27 | Completed | Sponsor: Mandos LLC | Active, not recruiting ➔ Completed | N=60 ➔ 27

Enrollment change • Trial completion • Genetic Disorders • Lysosomal Storage Diseases

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2 | N=3 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Feb 2022 ➔ Jun 2023 | Trial primary completion date: Feb 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders

Consistently High Agreement Between Independent Raters of Niemann-Pick Type C1 Clinical Severity Scale in Phase 2/3 Trial. (PubMed, Pediatr Neurol) - "These results support the NPC-SS, including derived four- and five-item composite scores, as reliable measures for use in a clinical trial setting."

Clinical • Journal • P2/3 data • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1 (clinicaltrials.gov) - P1/2; N=2; Completed; Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1 (clinicaltrials.gov) - P1/2; N=2; Active, not recruiting; Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Recruiting ➔ Active, not recruiting; N=30 ➔ 2

Enrollment change • Enrollment closed • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Adrabetadex to Treat Niemann-Pick Type C1 (NPC1) Disease (clinicaltrials.gov) - P2b; N=66; Active, not recruiting; Sponsor: Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company

Clinical • New P2b trial • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Adrabetadex for Patients With Nerve Symptoms of Niemann-Pick Type C Disease (NPC) (clinicaltrials.gov) - P3; N=60; Active, not recruiting; Sponsor: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company; Trial completion date: Jul 2021 ➔ Nov 2021; Trial primary completion date: May 2021 ➔ Oct 2021

Clinical • Trial completion date • Trial primary completion date

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C (clinicaltrials.gov) - P1/2; N=3; Active, not recruiting; Sponsor: Washington University School of Medicine; Recruiting ➔ Active, not recruiting; N=12 ➔ 3

Enrollment change • Enrollment closed • Frontotemporal Lobar Degeneration • Hepatology • Metabolic Disorders

Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1 (clinicaltrials.gov) - P2b; N=7; Active, not recruiting; Sponsor: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company; Enrolling by invitation ➔ Active, not recruiting

Clinical • Enrollment closed • Frontotemporal Lobar Degeneration • Metabolic Disorders

Adrabetadex for Patients With Nerve Symptoms of Niemann-Pick Type C Disease (NPC) (clinicaltrials.gov) - P3; N=60; Active, not recruiting; Sponsor: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-β-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1. (PubMed, CNS Drugs) - P1 | "In conjunction with previous findings, these results provide support for the slowing of disease progress up to 36 months post-initiation of intrathecal VTS-270."

Clinical • Journal • P1/2 data • CNS Disorders • Frontotemporal Lobar Degeneration • Metabolic Disorders

Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company; N=14 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Frontotemporal Lobar Degeneration • Metabolic Disorders • Pediatrics