Luxturna®, the only approved treatment for one of 27 identified forms of Leber congenital amaurosis (LCA), cost $500 million to develop and took more than 12 years to come to market.

With such an enormous investment in time and money, it would make sense to use that same platform for developing new treatments to improve vision or halt progression of blindness.

But that’s just not how it works, said Chad R. Jackson, PhD, Senior Director of the Foundation Fighting Blindness Preclinical Transitional Acceleration Research Program.

Every individual clinical study must complete a set of rigorous requirements – which cost time and money – to receive regulatory approval from the Food and Drug Administration (FDA).

The Foundation’s translational research program steps up the pace of preclinical studies toward clinical studies involving humans through proactive management and industry-level advice to drive research leading to prevention, treatment, and vision restoration for degenerative retinal diseases.

A Hope in Focus partner, the Foundation has raised nearly $900 million since its founding in 1971 and funds more than 90 programs worldwide, including no-cost genetic testing and the My Retina Tracker® patient registry. The Foundation also launched a Retinal Degeneration Fund (RD Fund) to help accelerate life-changing outcomes for people with retinal degenerations through direct mission-related investments in therapeutic companies.

Chad and other presenters shared information about drug development, gene therapies, and non-gene therapies during two sessions of the Hope in Focus 2023 LCA Family Conference* in Indianapolis this summer.

More than 100 people attended the forum to hear the latest in LCA research and to network with families living with LCA and other rare inherited retinal diseases (IRDs).

Bringing a drug from inception to market takes 10 to 15 years, Chad said, and costs tens and tens of millions of dollars. He said bringing a developing drug from preclinical studies to the FDA requires three steps:

Identify your target to know what you’re seeking to do; conduct invitro studies by expressing patient cells in a lab or as it’s referred to, retinas in a dish; and perform animal-model studies, which save time and money to determine whether emerging therapies are safe and perhaps ready to move toward clinical trials using humans.

Gene-Agnostic Therapies

Chad moderated a panel discussion about research moving beyond single-gene correction to gene-independent therapies to help delay progression of blindness or restore levels of vision.

Kiora Pharmaceuticals’ Chief Development Officer Eric J. Daniels, MD, MBA, discussed the company’s first-in-human study for a non-gene therapy treatment for retinitis pigmentosa (RP), a group of inherited eye diseases that cause progressive vision loss. It is characterized by the gradual death of light-sensitive photoreceptor cells in the retina, known as rods and cones, responsible for converting light into neutral signals sent to the brain.

Dr. Daniels said his company’s technology shifts retinal ganglion cells from their off state, in which they respond to decreases in light. Kiora has discovered a way to shift these cells into their on state in the presence of light through channeled photoswitch molecules.

According to Kiora, the mutation-agnostic treatment has the potential for use in any of the various genetic forms of RP, as well as other retinal degenerative diseases; its intravitreal injection allows for more consistent and tolerable administration, and the small molecule can be manufactured and provided to patients at a much lower expense than the $450,000 per eye cost of Luxturna.

Huma Qamar, MD, MPH, CMI, the head of Clinical Development and Medical Affairs for Ocugen, discussed the biotech’s work on treatments for LCA10 (CEP290), RP, and other IRDs. One of their clinical trials involves a novel gene therapy, OCU400, consisting of a functional copy of a nuclear hormone receptor gene delivered to target retinal cells using an adeno-associated viral (AAV) vector. Expression of this receptor within the retina may potentially help stabilize cells and rescue photoreceptor degeneration, Dr. Qamar said.

Ocugen demonstrated the potential of a novel modifier gene therapy to elicit broad-spectrum benefits in early and intermediate stages of RP and LCA, based on animal studies, showing the potential for a mutation-agnostic treatment.

Since the conference, Ocugen reported an update on its Phase 1/2 clinical trial for OCU400 for 12 patients who had follow-ups from six to 12 months after a subretinal injection in one eye. The developing drug had a favorable safety profile in this trial phase. Also eight of the 12 patients showed stabilization or improvement in the visual function measures of best corrected visual acuity, low-luminance visual activity, and navigating a multi-luminance mobility test.

The trial is currently enrolling patients, including pediatric patients with LCA10.

Gene Therapies

In the conference’s final session, moderated by Foundation Vice President of Science Communications Ben Shaberman, four panelists discussed their work on LCA gene therapies.

Shannon Boye, PhD, Co-Founder, Director, and Acting Chief Science Officer of Atsena Therapeutics, said the road to drug development is long and bumpy. She helped design early studies on LCA1 (GUCY2D) in 2001.

With the process going so slowly, Shannon reached out to then-Foundation CEO Ben Yerxa, who helped push her and her husband into starting their own company.

In 2019 doctors dosed the first patient. Earlier this year, in a Phase 1/2 clinical trial, their LCA1 gene therapy, known as ATSN-101, showed clinically meaningful improvements in vision at the highest dose with no drug-related serious adverse events at six months after treatment.

At Opus Genetics, Chief Scientific Officer Ash Jayagopal, PhD, discussed the biotech’s progress for various programs in, or advancing toward, early-stage clinical trials.

Opus, headed by CEO Ben Yerxa, PhD, is the first spin-out company internally conceived and launched by the Foundation’s RD Fund. The Fund’s purpose is to accelerate advancing research into gene therapy for several forms of LCA and other retinal degenerative diseases.

Opus’ most advanced program for LCA5 (lebercilin), OPGx-LCA5, is dosing patients, while two other LCA programs involving LCA13 (RDH12) and LCA9 (NMNAT1) are in preclinical development.

Thomas Mendel, MD, PhD, talked about his research at The Ohio State University, where he is Assistant Professor of Ophthalmology and Vitreoretinal Surgery at the university’s Havener Eye Institute, Department of Ophthalmology & Visual Sciences. He is building a research program to develop and implement gene therapies for  Professor of Ophthalmology and Vitreoretinal patients with inherited retinal disease.

The goal is to build a translational lab with a team and accelerate development and clinical trials with gene-based treatments.

Bikash R. Pattnaik, PhD, told the audience about his work at the University of Wisconsin-Madison (UWM), where he is a professor and Clinical Director for Electrophysiology in the departments of Pediatrics, Ophthalmology, and Visual Sciences.

This summer, the National Institutes of Health awarded UWM a $29 million grant to develop gene-editing therapies for two inherited retinal conditions: LCA16 (KCNJ13) and Best disease. Bikash said the LCA16 treatment in development could be in clinical trials next year.

*Please go to our Hope in Focus website to see our previous three stories detailing sessions from our 2023 LCA Family Conference. Click here to see a video about the conference.