Enriched Tear Film Gene Therapy Shows Promise for Ocular Surface Diseases


According to the company, preclinical study results from a 42-day proof-of-concept in vivo study demonstrated a single, intralacrimal gland injection of an adeno-associated virus containing the NGF gene produced statistically significant increase in NGF in tear film, as compared to placebo, as early as Day 7.

Oyster Point Pharma Inc. today announced the expansion of its pipeline with the introduction of Enriched Tear Film (ETF) Gene Therapy and proof-of-concept in vivo study results from its first gene therapy candidate, OC-101.

ETF Gene Therapy is a proprietary adeno-associated virus (AAV) based gene therapy approach where a

target gene is delivered to human lacrimal gland cells via intralacrimal gland injection.

Rather than replacing a gene that is defective or missing, a new target gene is delivered that potentially may produce a selected naturally occurring protein, enzyme, or other therapeutic gene product.

The goal for this target gene is to produce a selected gene product to change cell behavior and function on the ocular surface. Oyster Point’s investigational drug, OC-01 (varenicline) nasal spray, a highly selective cholinergic agonist, may play a role in ocular surface diseases treated with ETF Gene Therapy through its potential to modulate the secretion of a selected gene product.

In this proof-of-concept in vivo study evaluating OC-101 (AAV-NGF), a single, intralacrimal gland injection of an AAV containing the human NGF (hNGF) gene resulted in statistically significant levels of hNGF protein being expressed within the lacrimal gland and tear film of a rabbit model, as compared to control.

According to the company, hNGF was secreted into the tear film as early as 7 days after the intralacrimal gland injection. No control animals showed evidence of hNGF in the lacrimal gland or tear film. Additionally, three weeks following OC-101 (AAV-NGF) transduction of the lacrimal gland, cholinergic activation of the lacrimal gland with OC-01 (varenicline) nasal spray resulted in statistically significant increases in hNGF expression in the tear film, as compared to pre-cholinergic stimulation levels and as compared to control.

After cessation of OC-01 (varenicline) nasal spray, hNGF tear protein levels returned to pre-cholinergic activation levels (measured at Day 14). During the 42-day study, there were no macroscopic or microscopic safety findings observed associated with the intralacrimal gland administration of OC-101 (AAV-NGF) or OC-01 (varenicline) nasal spray.

“Oyster Point’s proprietary ETF Gene Therapy approach has shown the potential to increase basal levels

of NGF in the tear film and sustain NGF secretion onto the ocular surface as a part of the natural tear

film,” Jeffrey Nau, PhD, MMS, president and chief executive officer of Oyster Point Pharma., saind in a statement. “With additional preclinical studies underway, Oyster Point plans to meet with the FDA for a pre-IND meeting to discuss development of OC-101 (AAV-NGF) for patients with Stage 2 and Stage 3 neurotrophic keratopathy. In addition, Oyster Point will focus its Phase 2 OLYMPIA study of OC-01 (varenicline) nasal spray monotherapy on Stage 1 neurotrophic keratopathy patients.”

Eric Carlson, PhD, chief scientific officer of Oyster Point Pharma, the company believes that this is the first proof of concept study to show that a cholinergic agonist nasal spray (OC-01) has modulated protein secretion into the tear film after intralacrimal injection of an AAV-based gene therapy.

“We believe the translated protein may be processed and secreted in the same manner as endogenous proteins in the lacrimal gland by incorporating the proper post-translational modifications and folding,” he said in a statement. “Cholinergic stimulation of the lacrimal gland to increase secretion of tear film components and protein content may represent a potential new approach to treating a number of ocular surface diseases.”

The company will present proof of concept data at the upcoming Oyster Point Analyst Day, planned for July 15.

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