GEMMABio Announces First Patient Dosed in CHARISMA Trial of GB221, Investigational Next‑Generation Gene Therapy for Spinal Muscular Atrophy Type 1 (SMA1)

-U.S. FDA grants GB221 rare pediatric disease designation

PHILADELPHIA, Feb. 26, 2026 /PRNewswire/ -- Gemma Biotherapeutics ("GEMMABio"), a clinical‑stage global genetic medicines company, announced today that the first patient has been dosed in the Phase 1/2 CHARISMA clinical trial of GB221, an investigational, next‑generation gene therapy for SMA1.

The CHARISMA trial (NCT07070999) is the first clinical evaluation of a next‑generation gene therapy for SMA1 delivered directly to the cerebrospinal fluid (CSF) by intracisterna‑magna (ICM) injection.  Using proprietary, central nervous system (CNS) platform technology licensed from the University of Pennsylvania, GB221 was developed to express a functional, codon‑optimized SMN1 gene from a modified transgene expression cassette designed to reduce overexpression-related toxicities and sensory neurotoxicity.  The trial will evaluate safety, tolerability, and efficacy in pediatric participants from two weeks to younger than twelve months of age.  Cohorts will include symptomatic and presymptomatic participants.

"I would like to express our gratitude for the young child and family who were courageous in being the first to accept our investigational gene therapy for SMA1," said GEMMABio CEO James M. Wilson, MD, PhD, who also serves as a Member of the International Expert Advisory Board at Brazil's Casa dos Raros ("House of Rare").  "We appreciate our steadfast partners at Fiocruz / Bio-Manguinhos, Brazil Ministry of Health, ANVISA (Brazil health regulatory agency), Casa dos Raros, Intrials, and the Hospital de Clínicas de Porto Alegre medical team who worked with us and who demonstrated the tremendous potential of international public-private partnerships with designated regional Research and Treatment Centers (RTCs).  We anticipate expanding the CHARISMA clinical trial in Brazil and working together on future clinical trials for other rare disease gene therapies."

The SMA1 clinical activities are a core element in the partnership agreement between GEMMABio and the Oswaldo Cruz Foundation (Fiocruz) which was announced in October 2024.  Intrials, a contract research organization based in Brazil, is helping manage the clinical trials in the country.  Brazil serves as a regional hub in Latin America for GEMMABio's gene therapy programs.

"The medical team is monitoring the first patient carefully, hoping to see therapeutic benefit and progress towards developmental milestones," said Jonas Morales Saute, MD, PhD, who specializes in neurology and neurogenetics at the Hospital de Clínicas de Porto Alegre in Brazil and who is a principal investigator on the clinical trial.  "We are excited to leverage our experience in genetic diseases and clinical research to accelerate the development and evaluation of genetic medicines for other rare diseases."

"The ongoing clinical study opens a front of action that can transform the lives of families and children who deal with the disease on a daily basis," highlights Fiocruz President, Mario Moreira, PhD, MPH. "The technology incorporation agreement also guarantees the opening of pathways for access to an innovative gene therapy for the first time in the Unified Health System."

Recently, the U.S. FDA granted GB221 rare pediatric disease designation (RPDD).  Upon clinical trial completion, if GB221 meets criteria for a rare pediatric disease product application and the therapy is approved by the U.S. FDA, GEMMABio will be eligible to receive a priority review voucher (PRV).  The recently reauthorized Rare Pediatric Disease Priority Review Voucher Program was renewed by the U.S. Congress in the Consolidated Appropriations Act of 2026 and will be in effect through September 2029 (requiring congressional reauthorization to extend that date).  The PRV may be used by the original recipient to obtain a quicker FDA review of a future drug, or it can be sold to another company for their use in securing a priority review.  The program is intended to incentivize the development of new therapies for rare pediatric diseases.

For information on the clinical trial design for GB221, please visit ClinicalTrials.gov.

About GB221
GB221 is an investigational, next‑generation gene therapy for SMA1 developed to express SMN1 in motor neurons.  The absence of functional SMN1 protein in motor neurons is the underlying cause of SMA.  GB221 is a one-time gene therapy that consists of an adeno‑associated virus (AAV) human isolate, AAVhu68, encasing a functional copy of a codon‑optimized SMN1 gene in a modified transgene expression cassette designed to reduce overexpression and sensory neurotoxicity.  It is delivered directly to the cerebrospinal fluid (CSF) via intra-cisterna magna (ICM) injection.

The proprietary central nervous system (CNS) platform technology was developed by Dr. Jim Wilson's research team and licensed from the University of Pennsylvania.

About CHARISMA
CHARISMA (NCT07070999) is a first‑in‑human clinical study of GB221 in SMA1 that will evaluate safety, tolerability, and efficacy in pediatric participants.  Additional details can be found at ClinicalTrials.gov.

About SMA1
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that affects motor neurons in the spinal cord and adversely affects the skeletal muscles.  Progressive muscle weakness impairs breathing, eating, crawling/walking, and other activities.  SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1), and it follows an autosomal recessive pattern of inheritance.  The global incidence of all types of SMA, whose severity is modulated by the number of SMN2 gene copies, is approximately 1:10,000 live births.

SMA Type 1 (SMA1) is a very severe form with early onset and diagnosis occurring at less than 6 months of age.  Untreated SMA1 patients do not survive beyond 18 months of age.  SMA1 patients typically have 1-2 copies of the SMN2 gene.  The global incidence of SMA1 is approximately 1:17,000 live births.

About GEMMABio
GEMMABio is a clinical-stage therapeutics company focused on speeding the research of and global access to life-changing advanced therapies for those living with rare diseases.  The company conducts research and product development functions to bring gene therapy discoveries from the bench to the bedside faster and affordably.  GEMMABio is led by gene therapy industry pioneer Jim Wilson and his team of experts, who previously conducted their work in academia. Learn more about GEMMABio at gemmabiotx.com and follow us on LinkedIn.

University of Pennsylvania Financial Disclosure
The University of Pennsylvania ("Penn") owns an equity interest in GEMMABio.  Penn has either received, or may receive in the future, financial consideration related to the licensing of certain Penn intellectual property to GEMMABio.

SOURCE GEMMA Biotherapeutics