Pipeline

New hope for people with previously untreatable central nervous system disorders

Our gene therapy portfolio spans pediatric and adult CNS indications. We are advancing lead clinical programs in GM1 gangliosidosis and frontotemporal dementia (FTD) and have built a promising preclinical pipeline including candidates for amyotrophic lateral sclerosis (ALS) and Huntington’s disease.

A FOCUSED PIPELINE OF PROMISING GENE THERAPIES

Program*

Indication

Gene

Discovery
Pre-clinical
Phase 1/2
Pivotal

Program*
PBFT02

Indication: Frontotemporal
dementia

Gene: GRN

Details

Our gene therapy product candidate, PBFT02, an AAV1 viral vector to deliver a modified DNA encoding the granulin gene (GRN) to a patient’s cells. The vector will be delivered directly to the cerebrospinal fluid by a single injection to the cisterna magna (ICM injection). The goal of this vector and delivery approach is to provide higher-than-normal levels of the progranulin protein (PGRN) to the CNS to overcome the progranulin deficiency in GRN gene mutation carriers.

Related link

Learn more about frontotemporal dementia

Program*
PBGM01

Indication: GM1
gangliosidosis

Gene: GLB1

Details

Our gene therapy product candidate, PBGM01, utilizes an AAVhu68 viral vector to deliver a codon-optimized gene sequence encoding functional β-gal enzyme. The vector will be delivered directly to the cerebrospinal fluid by a single injection to the cisterna magna (ICM injection), with the goal of increasing β-gal enzyme activity levels in both the central nervous system and periphery.

Related link

Learn more about GM1 gangliosidosis

Program*
PBAL05

Indication: Amyotrophic
lateral sclerosis

Gene: C9orf72

Details

We are developing PBAL05 to treat amyotrophic lateral sclerosis (ALS), a motor neuron disease characterized by rapid degeneration of upper and lower motor neurons, leading to progressive weakness and premature death. We are targeting ALS patients who have a gain-of-function mutation in the C9orf72 gene. Most cases of ALS are sporadic with an unknown etiology, but there are also genetic forms of the disease inherited in an autosomal dominant fashion. Mutations in the C9orf72 gene are the most common genetic defects implicated in ALS, accounting for approximately 34% of familial ALS cases and approximately 5% of sporadic ALS cases.

Program*
Unnamed

Indication: Huntington’s Disease

Gene: HTT & Undisclosed

Program*
Unnamed

Indication: Temporal lobe epilepsy

Gene: Undisclosed

Program*
PBKR03

Indication: Krabbe disease

Gene: GALC

Details

Our gene therapy product candidate, PBKR03, utilizes an AAVhu68 viral vector to deliver a functional GALC enzyme gene that codes for galactosylceramidase (GAL-C). The vector will be delivered directly to the cerebrospinal fluid by a single injection to the cisterna magna (ICM injection), with the goal of increasing levels of the GALC enzyme in both the central nervous system (CNS) and the peripheral nervous system (PNS).

Program*
PBML04

Indication: Metachromatic
leukodystrophy

Gene: ARSA

Details

We are developing PBML04 to treat metachromatic leukodystrophy (MLD), a recessive lysosomal storage disease caused by genetic mutations that result in demyelination of the fibers of the central and peripheral nervous systems, leading to progressive motor and cognitive impairments. We are developing PBML04 for patients who have MLD and mutations in the enzyme ARSA gene, which encodes the lysosomal enzyme ARSA.

*8 additional CNS pipeline options remain; 3 license options were previously exercised, and rights were subsequently returned to the University of Pennsylvannia
Program includes ongoing natural history study of infantile and juvenile GM1 gangliosidosis patients.