Our Pipeline

We currently have four ongoing clinical programs, including Phase 1/2 clinical stage programs in Achromatopsia (ACHM), X-Linked Retinitis Pigmentosa (XLRP) and RPE65-Deficiency, and a Phase 1 program in radiation induced xerostomia (RIX). In addition, we anticipate initiating a clinical program in xerostomia related to Sjogren’s syndrome in 2019 and have preclinical programs in neurodegenerative diseases.

Ocular Programs

Product Candidate

AAV-CNGB3

Indication

Achromatopsia
(CNGB3)

Phase

Phase 1/2

AAV-CNGB3, a gene therapy treatment designed to restore cone function, is delivered via subretinal injection to the area of the eye where most of the cones in the retina are located. Our CNGB3 gene therapy product candidate, AAV-CNGB3, was granted orphan drug, rare pediatric disease and Fast Track designations by the FDA, and orphan drug and PRIME designations by the EMA for the treatment of achromatopsia caused by mutations in the CNGB3 gene. We are currently conducting a Phase 1/2 clinical trial of AAV-CNGB3 in both adult and pediatric patients.

ACHM is an inherited retinal disease that specifically prevents cone photoreceptors from functioning. ACHM patients are legally blind from birth and usually suffer from severely reduced visual acuity of 20/200 or worse, a disabling sensitivity to light, or photophobia, total color blindness and involuntary back and forth eye movements, or nystagmus. ACHM occurs in approximately one in 30,000 people in the United States.

Product Candidate

AAV-CNGA3

Indication

Achromatopsia
(CNGA3)

Phase

Phase 1/2

AAV-CNGA3, a gene therapy treatment designed to restore cone function, is delivered to the cone receptors at the back of the eye via subretinal injection. Our AAV-CNGA3 gene therapy product candidate was granted orphan drug designation in the United States and European Union, as well as rare pediatric disease designation in the United States. It was designed with a synthetic promoter associated with strong gene expression to account for the larger amount of protein needed to restore cone function in patients with a CNGA3 mutation.

ACHM is an inherited retinal disease that specifically prevents cone photoreceptors from functioning. ACHM patients are legally blind from birth and usually suffer from severely reduced visual acuity of 20/200 or worse, a disabling sensitivity to light, or photophobia, total color blindness and involuntary back and forth eye movements, or nystagmus. ACHM occurs in approximately one in 30,000 people in the United States.

Product Candidate

AAV-RPE65

Indication

RPE65-Deficiency
(RPE65)

Phase

Phase 1/2

AAV-RPE65 is a gene therapy product candidate in which expression of a codon-optimized RPE65 gene is driven by a novel synthetic retinal pigment epithelium (a thin layer of cells at the back of the eye) cell-specific promoter.  The RPE65 protein is essential for rod function because it recycles the light sensing machinery in rod photoreceptors. The codon and vector optimization resulted in a gene therapy that is 100 to 1,000 times more potent than the first generation therapy. The FDA and EMA each granted orphan status to AAV-RPE65 for the treatment of Leber’s Congential Amaurosis (LCA). The FDA also granted AAV-RPE65 rare pediatric disease designation for the treatment of inherited retinal dystrophy due to biallelic RPE65 mutations. We are currently conducting a Phase 1/2 clinical trial of AAV-RPE65 in both adult and pediatric patients.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders (IRDs) which represent the most common genetic cause of blindness. The condition is characterized by progressive retinal degeneration and vision loss that ends in complete blindness. There are currently no approved treatments for RP. RP initially presents as nighttime blindness during childhood or early adulthood, progressing to peripheral visual field loss and “tunnel vision,” central visual impairment, reduced visual acuity and, ultimately, complete blindness.

Product Candidate

AAV-RPGR

Indication

X-linked RP
(RPGR)

Phase

Phase 1/2

AAV-RPGR, is designed to treat the most common form of XLRP caused by mutations in the eye-specific form of the RPGR gene called RPGR open reading frame 15 (RPGR-ORF 15). Both rods and cones photoreceptors require RPGR-ORF 15 to function. AAV-RPGR has received Fast Track and Orphan Drug designations from the U.S. FDA and Orphan Medicinal Product designation from the European Medicines Agency (EMA). We are currently conducting a Phase 1/2 clinical trial of AAV-RPGR in adult and pediatric patients.

X-linked retinitis pigmentosa (XLRP) represent some of the most severe forms of RP, resulting in early onset in childhood and rapid progression to blindness by the time patients reach 20 to 30 years old. In XLRP, both rods and cones function poorly, leading to degeneration of the retina and total blindness. There are currently no approved treatments for XLRP.

Salivary Gland Programs

Product Candidate

AAV-AQP1

Indication

Xerostomia
(hAQP1)

Phase

Phase 1/2

We are developing AAV-AQP1 to treat radiation-induced xerostomia (RIX) by increasing water conduction in the salivary glands damaged by radiation therapy. The gene therapy works by introducing a water conducting channel into the remaining epithelial cells of these damaged glands. We are currently conducting a Phase 1 clinical trial in patients who have survived cancer free for five or more years following treatment for head and neck cancer and are suffering from grade 2 or 3 radiation-induced late xerostomia.

 

Xerostomia is a chronic and debilitating disorder of the salivary glands in which saliva production is impaired. Xerostomia has a number of different potential causes, including radiation therapy for head and neck cancer and certain autoimmune diseases. The fluid secreting, or acinar cells, of the salivary glands are uniquely sensitive to radiation, resulting in chronically reduced salivary output. Because saliva plays such a critical role in the physiology and protection of upper gastrointestinal tract tissues, patients with chronic RIX suffer severe long-term complications that have a significant impact on the patient’s daily living, including difficulty swallowing, or dysphagia, oral discomfort, malnutrition, oral mucositis, changes in taste, increased oral infections and dental cavities.

Product Candidate

AAV-AQP1

Indication

Sjogren’s
(hAQP1)

Phase

Preclinical

We are developing AAV-AQP1 to Sjogren’s syndrome, a disease affecting more than two million people in the United States. Sjogren’s syndrome is an autoimmune disease in which a patient’s immune system may target the salivary glands. Chronic inflammation of the salivary glands results in long term damage and chronic xerostomia in many Sjogren’s patients.

We intend to initiate a Phase 1/2 clinical trial for the treatment of patients with chronic xerostomia caused by Sjogren’s syndrome in 2019.

Neurodegenerative Diseases Program

Product Candidate

AAV-UPF1

Indication

ALS
(UPF1)

Phase

Preclinical

We have designed our product candidate, AAV-UPF1, with the aim of increasing UPF1 expression in the motor neurons of ALS patients. UPF1 plays an important role in nonsense mediated decay (NMD), a quality control system that regulates RNA processing in neurons. AAV-UPF1 is currently being investigated in preclinical studies.

ALS is a devastating, progressive, neurodegenerative disease leading to the loss of motor neurons, which are the neurons that control the ability to move, speak, swallow and ultimately to breathe. The gradual paralysis in ALS invariably leads to death. While 10 percent of ALS cases are caused by inherited genetic mutations, most ALS occurs sporadically, with no known genetic cause. Mutations in over 20 genes have been identified that cause the inherited ALS cases. Characterization of these disease-causing genes have implicated several cellular pathways in the disease, with a prominent role emerging for genes involved in the cellular control of RNA. Many new regulatory roles are being discovered for RNA, particularly in neurons.