Therapeutic Areas

Our initial focus is on three distinct areas of unmet medical need: eye, neurodegenerative and salivary gland diseases. We selected these areas based on the lack of currently available treatments coupled with the high potential gene therapy has to provide meaningful clinical benefit in these areas.


We currently have four ongoing clinical programs in inherited retinal diseases, along with our compassionate use program for LCA-AIPL1 in the UK. Our four ongoing clinical stage programs include: RPE65-deficiency, Achromatopsia (ACHM) caused by mutation in both the CNGB3 and CNGA3 genes, and X-Linked Retinitis Pigmentosa (XLRP). We are currently enrolling patients in our ACHM (CNGA3) Phase 1/2 dose escalation trial and our XLRP Phase 1/2 does escalation trial expansion cohort. Phase 1/2 dose escalation trials have been completed in RPE65 and ACHM (CNGB3) with follow-up ongoing.


RPE65-deficiency is a rare, genetic disorder caused by variants in the RPE65 gene. Due to rod photoreceptor dysfunction, RPE65-deficiency causes impaired vision from birth and results in the degeneration of the entire retina over time. Most RPE65-deficient patients experience poor vision in low-light conditions from a young age and suffer from central vision loss that progresses to complete blindness by early adulthood.

RPE65-deficiency is often characterized as a specific subtype of LCA (LCA2), or a specific subtype of Retinitis Pigmentosa (RP20).

RPE65-deficiency occurs in approximately one in 125,000 people in the U.S.2There are estimated to be approximately 6,000 RPE65-deficient patients in the U.S., Japan and EU5, with almost 30% of those patients under the age of 30 years old. Approximately 50 new cases are diagnosed annually.


Achromatopsia (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. To date, mutations of any one of six genes encoding components of the light sensing machinery of cone photoreceptors have been identified as causing ACHM. The CNGB3 and CNGA3 genes are the two most common of these genes, together accounting for up to 92% of ACHM cases.1

Retinitis Pigmentosa

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.

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.

In addition to these clinical programs, we have preclinical programs that apply novel approaches to both wet and dry AMD.

1Koma´romy, A., Alexander, J., Rowlan, J., Garcia, M., Chiodo, V., Tanaka, J., Acland, G., Hauswirth, W., & Aguirre, G. (2010). Gene therapy rescues cone function in congenital achromatopsia. Human Molecular Genetics, 19(13), 2581–2593. doi: 10.1093/hmg/ddq136
2 Based on an estimated prevalence of approximately one in 500,000 people in the U.S. with LCA related to disease-causing variants in the RPE65 gene, and approximately one in 70,000 people in the U.S. with RP due to disease-causing variants in the RPE65 gene.

Neurodegenerative Disease

Neurodegenerative diseases are our second area of focus with research programs targeting amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease.

Parkinson’s Disease

Affecting nearly one million Americans and 10 million people worldwide, Parkinson’s disease is the second-most common neurodegenerative disease after Alzheimer’s disease, and the 14th-leading cause of death in the United States. It is associated with a progressive loss of motor control (e.g., shaking or tremor at rest and lack of facial expression), as well as non-motor symptoms (e.g., depression and anxiety). There is no cure for Parkinson’s disease and 60,000 new cases are diagnosed each year in the United States alone.


Amyotrophic lateral sclerosis (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.3 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. We believe that dysregulation of neuronal RNA processes results in the degeneration of motor neurons that leads to ALS. Rather than targeting a specific genetic defect that defines a small subset of ALS patients, we aim to target the underlying cell biology driving motor neuron death in ALS, potentially enabling us to treat both sporadic and inherited forms of the disease.

Alzheimer’s Disease

With the world population aging, Alzheimer’s disease has emerged as a common and costly disease. Two biological pathways have been identified that are considered causes of Alzheimer’s disease: (i) misprocessing of amyloid precursor protein (APP) caused by genetic defects in APP itself and the APP processing proteins presenilin 1 and 2 and (ii) the movement, or trafficking, of cellular protein which is controlled by a cell component called the endosome.

Over the past decade, evidence has emerged supporting endosomal trafficking dysfunction in neurons as a central process in Alzheimer’s disease. Our Alzheimer’s disease program is directed towards endosomal trafficking as an underlying cell biology of the disease.

3 Taylor, J., Brown Jr., R., & Cleveland, D. (2016). Decoding ALS: from genes to mechanism. Nature, 539, (197–206). doi:10.1038/nature20413

Salivary Gland

Our third area of clinical focus is xerostomia, 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.

Radiation as a treatment for head and neck cancer can cause irreversible damage to non-diseased tissues located near oral tumors, such as the salivary glands. 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 radiation-induced xerostomia (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.

There is currently no FDA approved treatment for RIX. Worldwide, there are approximately 500,000 new cases of head and neck cancer diagnosed each year, with approximately 50,000 cases in the United States alone, making it the fifth most common malignancy.4 Approximately 40% of patients who remain cancer free for two or more years after radiation treatment for head and neck cancer suffer from grade 2 or 3 RIX.5 There are approximately 170,000 of these patients in the United States, with approximately 10,000 new cases each year.6

We have an ongoing Phase 1 clinical trial and a second multi-site Phase 1/2 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.

4Howlader N., et al. (eds). SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda, MD,, based on November 2010 SEER data submission, posted to the SEER web site, 2011.
5Jensen S.B., et al. (2010). A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer. 18(8):1039-1060.
6Cox J.D., et al. (1995). Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment for Cancer (EORTC). Int. J. Radiation Oncology Biol. Phys. 31(5):1341-1346