Iveric Bio Expands into Gene Therapy for Untreated Retinal Diseases

Gene Therapy

When Iveric Bio established its gene therapy advisory committee recently, the move signaled the opening of a second front in its mission to treat retinal diseases for which there are no treatments.

“Retinal medicine is an extremely nuanced field, so we needed the best of the best scientists and clinicians out there,” said Pravin U. Dugel, M.D., president of Iveric Bio. “We established the committee once the basic science matured. Now we’re at the precipice of putting retinal gene therapy into humans.”

The mission of the Gene Therapy Inherited Retina Disease Scientific Advisory Committee is to translate the science to the clinic.

“A lot of companies miss the translation aspect. Just because the science is valid in the lab and in pre-clinical studies, doesn’t necessarily mean it will be adapted to the clinic,” Dugel told BioSpace.

“The committee’s insights also will help us prioritize our pipeline and design clinical trials to be more impactful,” he added. For example, determining clinical impact “isn’t as simple as checking vision. The visual acuity, which is a measure only of the central retina, may not improve in first-in-human studies and may not be the appropriate biomarker for some diseases.”

Instead, better trial endpoints may be multi-luminance mobility testing, microperimetry, quality of life questionnaires, etc., depending on the target disease. Choosing the appropriate biomarkers, such as reading speed, contrast sensitivity, or other elements would offer meaningful improvements to people who are going blind. Also, the factors that are meaningful to an 85-year-old patient may be different than those of a 14-year-old, he pointed out.

Iveric Bio was founded by retinal specialists. Before joining Iveric Bio 18 months ago and recently becoming president of the company, Dugel himself was a practicing retinal specialist and remains an internationally known physician.

He is a clinical professor at the USC Roski Eye Institute, Keck School of Medicine, University of Southern California; has served as a visiting professor in some 16 nations; and has been the principal investigator in more than 100 multicenter trials. He received the Senior Honor Award from the American Academy of Ophthalmology and has served as a board member for the largest retina society in the United States, the American Society of Retina Specialists (ASRS), and the largest retina society in Europe, EURETINA.

In selecting the gene therapy advisory committee, therefore, “we weren’t starting from scratch. The retinal world is small. There are only 2,500 retinal specialists in the U.S., and everybody knows everybody. They each have a certain niche,” he said.

Dugel has worked with many of these committee members before joining the company and has known many throughout his professional life. This collegiality is expected to enhance Iveric Bio’s gene therapy program.

Members of the new Gene Therapy Inherited Retina Disease Scientific Advisory Committee are:

  • Elias Traboulsi, M.D., head, department of pediatric ophthalmology and director of the Center for Genetic Eye Diseases at the Cole Eye Institute, and professor of Ophthalmology at the Cleveland Clinic
  • Andreas K. Lauer, M.D., chair, department of ophthalmology, Casey Eye Institute, Oregon Health & Science University
  • Bart P. Leroy, M.D., Ph.D., head, department of ophthalmology, Ghent University Hospital, and director of the retinal degenerations clinic at Children’s Hospital of Philadelphia
  • Mark Pennesi, M.D., Ph.D., division chief, ophthalmic genetics and associate professor in ophthalmology, Oregon Health & Science University 
  • Eleonora Lad, M.D., Ph.D., director of grading, Duke Reading Center, and associate professor of ophthalmology, Duke University Medical Center

The gene therapy program on which they are advising currently has five different products, all in the pre-clinical and research phases. The furthest along are IC-100 for RHO-adRP and IC-200 for best1-related retinal diseases. For IC-200, a Phase I/II trial is planned for the second half of this year.

The remaining programs are miniCEP290 for Leber’s congential amaurosis type 10; miniABDA4 for autosomal recessive Stargardt disease; and miniUSH2A for Usher’s syndrome Type 2A. They are dubbed “mini-gene” programs because, in these programs, the naturally occurring gene is larger than the capacity of the standard adeno-associated viral (AAV) vector used for gene therapy. Iveric Bio, therefore, is working to develop smaller gene constructs to enable AAV gene delivery.

The company also has two therapeutic product candidates in development. One, Zimura® (avacincaptad pegol), is in development for the treatment of geographic atrophy secondary to macular degeneration.

“Zimura currently is being studied in a Phase III clinical program, and if results at 12 months are positive, we plan to submit Zimura to the FDA for final approval in this indication,” Dugel said.

Zimura® also is in a Phase IIb clinical trial to treat autosomal recessive Stargardt disease.

The other product candidate, IC 500, is an HtrA1 inhibitor. It is designed to stop the progression of macular degeneration and is in preclinical development.

“When I entered this field, about 30 years ago, treatments for retinal diseases were almost entirely surgical. We couldn’t do anything for macular degeneration or most inherited diseases. We could repair retinal detachments, but were unable to treat most of the medical problems we encountered,” Dugel recalled. “Since then, there’s been astonishing progress in this field.”

Many of the advances have been in wet macular degeneration.

“We’re not doing that. We are focusing on diseases for which there is no treatment,” Dugel told BioSpace. Retinal conditions with unmet needs are not necessarily rare, either. “The biggest cause of blindness is dry macular degeneration, yet there’s no treatment for that.”

He’s hoping Zimura® will solve that.

These two silos, therapeutics and gene therapy, will help Iveric Bio expand its footprint in the retinal arena. The ultimate goal is to uphold Iveric Bio’s mission statement: to develop transformative therapies for retinal diseases.

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