Melpida / CureSPG50, Elpida Therap - LARVOL DELTA

AAV9/AP4M1-DK01: A Phase IIb, Non-Profit, Open-label Trial for the Intrathecal Administration of AAV9/AP4M1 for Hereditary Spastic Paraplegia Type 50 (SPG50) (clinicaltrialsregister.eu) - P1/2 | N=2 | Not yet recruiting | Sponsor: Rigshospitalet, Elpida Therapeutics SPC

New P1/2 trial • Genetic Disorders

Preliminary safety results from a phase I/II open label gene therapy trial of Spastic Paraplegia 50 (NCT05518188) (ASGCT 2026) - P1/2 | "An immunomodulatory regimen (corticosteroids, sirolimus, and tacrolimus) was implemented to allow inclusion of both CRIM- and CRIM+ patients...There have been 10 serious adverse events (SAEs) reported of which 7 were attributed to MELPIDA...Conclusion Preliminary results from the phase I/II study demonstrate that AAV9/AP4M1 was well tolerated in children with SPG50, with a manageable side effect profile. This investigational therapy may be a promising option for this ultra-rare disease."

Clinical • Gene therapy • P1/2 data • CNS Disorders • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Inflammation • Mental Retardation • Movement Disorders • Neutropenia • Otorhinolaryngology • Rare Diseases • Respiratory Diseases

AAV9/AP4M1-ITA-01: Administration of a new gene therapy to patients affected by Hereditary Spastic Paraplegia Type 50 (SPG50) (clinicaltrialsregister.eu) - P1/2 | N=5 | Not yet recruiting | Sponsor: Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

New P1/2 trial • Gene Therapies • Genetic Disorders

Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls. (clinicaltrials.gov) - P3 | N=24 | Recruiting | Sponsor: Elpida Therapeutics SPC | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

A father's crusade in rare disease drug development: a case study of Elpida therapeutics and Melpida. (PubMed, Orphanet J Rare Dis) - "We identify the factors that led to the success of Melpida and analyze the business model of Elpida Therapeutics, a social purpose corporation founded by Pirovolakis to reproduce the success of Melpida for other rare diseases. We conclude with four lessons from Melpida to inform caregivers like Pirovolakis on developing novel gene therapies to save their loved ones."

Journal • Gene Therapies • Rare Diseases

A Unique Model for Accelerating Drug Development and Clinical Trials towards Drug Approvals in Rare Pediatric CNS disorders (ASGCT 2025) - "Our lead clinical-stage program for SPG50 disease has progressed through clinical phases in half the time of traditional pipelines, and our lead product MELPIDA currently at Phase 3 trials. Our strategy at Elpida Therapeutics exemplifies a novel and highly effective approach to drug development in rare CNS disorders where there is a limited patient population and a significant unmet medical need. This model not only promises to shorten timelines but also aims to make the drug development process more patient-centric, cost-effective, and scalable for the future of precision medicine in rare diseases."

Clinical • Late-breaking abstract • CNS Disorders • Pediatrics • Rare Diseases

Phase 3, Open-label Study to Assess the Efficacy and Safety of a Single Lumbar Intrathecal Administration of MELPIDA in Individuals with Hereditary Spastic Paraplegia Type 50 (SPG50) Versus Matched Prospective Concurrent Controls. (clinicaltrials.gov) - P3 | N=24 | Not yet recruiting | Sponsor: Elpida Therapeutics SPC

New P3 trial • Genetic Disorders

Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50 (clinicaltrials.gov) - P1 | N=1 | Active, not recruiting | Sponsor: The Hospital for Sick Children

New P1 trial • Genetic Disorders

Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt) (clinicaltrials.gov) - P1/2 | N=2 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Movement Disorders • Muscle Spasticity

Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt) (clinicaltrials.gov) - P1/2 | N=2 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center | Initiation date: Oct 2022 ➔ Jan 2023

Trial initiation date • Genetic Disorders • Movement Disorders • Muscle Spasticity

Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt) (clinicaltrials.gov) - P1/2 | N=2 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center

New P1/2 trial • Genetic Disorders • Movement Disorders • Muscle Spasticity