AAV gene therapy for Krabbe disease is 100% effective

Forge Biologics recently announced the latest clinical data
of its Phase 1/2 RESKUE for the treatment of Krabbe's disease in AAV gene therapy FBX-101 at the 29th Congress of the European Gene Therapy Association (ESGCT).

Key information:

• Chief Medical Officer Maria Escolar, MD, will present clinical data demonstrating the safety and efficacy of the RESKUE trial at the 29th European Society for Gene and Cell Therapy (ESGCT) Congress from 11 to 14 October 2022
• Subjects treated with FBX-101 showed increased galactocerebrosidase (GALC) enzyme activity, normal white matter myelination, and normalization of motor development in plasma and cerebrospinal fluid (CSF) at 90 days and 9 months after treatment
• FBX-101 is well tolerated, has no serious adverse events associated with treatment, and has no humoral reaction to the vehicle after intravenous administration
• The company will also present data at the Alliance for Regenerative Medicine (ARM) Cell and Genomics Conference in Carlsbad, California, on October 12, 2022 at 9:15 a.
  m.
  PT

RESKUE is the first human clinical trial in which patients with Krabe's disease receive FBX-101, a systemic gonad-associated virus (AAV) gene replacement strategy
after complete myeloablation and hematopoietic stem cell transplantation (HSCT).
Krabbe is a rare inherited neurodegenerative leukodystrophy that affects the central nervous system (CNS) and peripheral nervous system (PNS).

Crabberg disease affects infants with an incidence of 1 to 2.
5 per 100,000 and leads to premature death, usually 2 years of age
.
Clinical data support preclinical observations that this gene therapy approach after HSCT may alleviate many of the immune challenges previously observed in systemic AAV gene delivery and may create a safer environment
for gene replacement.
The findings also support this new approach for scaling the delivery of gene replacement strategies to target metabolic diseases
suitable for HSCT.

Data from treatment subjects suggest that intravenous FBX-101 after HSCT is safe and well
tolerated.
Notably, data indicate that there is no humoral immune response against systemically delivered AAV, and significant increases in galactocerebrosidase (GALC) enzyme activity
have been observed in plasma and cerebrospinal fluid (CSF).
Krabbe disease is characterized by mutations in the GALC gene, resulting in loss
of motor function.
All subjects treated to date have also shown improved motor activity and normal brain development, which would not have been expected in the absence of
systematic gene transfer of the GALC gene.

"We are pleased to present data from multiple patients in our RESKUE trial and are encouraged by the safety and efficacy results observed in FBX-101-treated subjects," said
Dr.
Escolar.
"An update of our first cohort data indicates that intravenous FBX-101 is safe and well tolerated after HSCT, including increased GALC enzyme activity in plasma and CSF, normal white matter myelination, and normalization
of motor development.
The results are exciting and offer hope for patients with Krabe's disease, who often don't live to be two years
old without treatment.
”

Dr.
Escolar's presentation, "Intravenous FBX-101 (AAVrh10.
hGALC) Increases GALC Activity, Supports Brain Development, and Improves Motor Function in Infant Krabey Disease Patients After Hematopoietic Stem Cell Transplantation: RESKUE Phase 1/2 Clinical Trial" is available to all ESGCT participants
from October 11 to October 14, 2022.

Dr.
Timothy J.
Miller, CEO, President, and Co-Founder of Forge, will also share clinical data during a corporate presentation at the Regenerative Alliance on Wednesday, October 12, 2022 at 9:15 a.
m.
PT at the Medical (ARM) Cell & Gene Conference
in Mesa, Carlsbad, California.

About Krabbe disease

Krabbe disease is a rare neurodegenerative disease that affects
approximately 1-2.
5 people per 100,000 people in the United States.
It is a rare autosomal recessive neurodegenerative disease caused by loss-of-function mutations in the lysosomal enzyme galactosylceramisase (GALC) gene, which causes the accumulation of certain lipids (such as psychosine) in cells and causes the death of myelin cells of the brain and peripheral nervous system, resulting in loss
of motor function.
Without functional GALC, psychosine accumulates in cells to toxic levels, particularly in cells that isolate the nerves of the brain and peripheral nervous system, leading to rapid demyelination
.
Krabbe disease initially presents with irritability, developmental delay, and progressive muscle weakness; Symptoms rapidly progress to dysphagia, dyspnea, worsening developmental delays, and vision and hearing loss
.
Infantile Krabbe disease (0 to 12 months of age at onset) usually causes untreated patients to die
at age 2 years.
Patients with advanced infant disease (12 to 36 months of age at onset) usually die
at age 6 years.
The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes
when performed before symptom onset.
However, HSCT does not correct peripheral neuropathy that progresses as the patient grows, leading to loss of gross motor skills and eventual death
.
Early diagnosis is key
to treating patients with Krabbe before severe nerve damage occurs.
Currently, 10 states in the United States are screening
newborns for Clabeth's disease.
Infants who screen positive means that insufficient GALC activity is detected, and psychotropin and mutation analysis is performed to confirm the diagnosis and predict the onset
of disease.

About FBX-101

FBX-101 is an adeno-associated virus serotype rh10 (AAVrh10) gene therapy administered intravenously after hematopoietic stem cell transplantation (HSCT) to deliver functional copies of the GALC gene to cells of the central and peripheral nervous systems to encode the desired enzyme.

In animal models, FBX-101 has been shown to functionally correct central and peripheral neuropathy and significantly extend animal lifespan
.
The results also show that systemic AAV gene delivery after HSCT is expected to overcome the safety challenges of traditional AAV immunology and create a safer environment
for gene replacement.

Data from this trial showed that patients showed increased activity in plasma and cerebrospinal fluid (CSF) in plasma and cerebrospinal fluid (CSF) after 90 days and 9 months of treatment with FBX-101, normal white matter myelination, and all subjects also showed improved motor function and normal brain development
.
In addition, FBX-101 was well tolerated, there were no treatment-related serious adverse events, and no humoral immune response was
observed.
The efficacy and safety
of FBX-101 in the treatment of Krabbe disease has been preliminarily demonstrated.

Resources: