Forty High-Impact Retinal-Research Efforts Highlighted at FFB-Casey Innovation Summit

Hosted by the Foundation Fighting Blindness and Casey Eye Institute at Oregon Health & Science University, the Innovation Summit for Retinal Cell and Gene Therapy has emerged as one of the most essential events for researchers and companies developing treatments and cures for retinal degenerative diseases.
In its fifth year, the Innovation Summit featured 40 presentations from industry experts from around the world. More than 250 people were in attendance. The event was held on April 27, the day before the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Honolulu.

Spark Therapeutics, Applied Genetic Technologies Corporation (AGTC), REGENXBIO, and Nightstar Therapeutics sponsored the event.
Summit co-hosts were Casey’s Mark Pennesi, MD, PhD, and Trevor McGill, PhD, and Steven Rose, PhD, FFB’s chief scientific officer.
While the ARVO meeting is the world’s largest eye research conference with about 12,000 attendees, the Innovation Summit provided an unparalleled focus on potential therapies, many of which are in clinical trials, for the entire spectrum of retinal degenerative diseases.
Here are summaries of the meeting presentations:
Cell Therapy Presentations

  • On behalf of the California Project to Cure Blindness, Dennis Clegg, PhD, and Amir Kashani, MD, PhD, presented the interim results of Regenerative Patch Technologies Phase 1/2a safety study on the implantation of a human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) graft in subjects with advanced, dry age-related macular degeneration (AMD). RPE provides support for photoreceptors and is lost early in AMD progression. The RPE is on an ultrathin synthetic parylene membrane. The implant is designed to replace the retinal pigmented epithelium (RPE) and Bruch’s membrane which are critical functional elements of the eye that degenerate in dry AMD,. Initial results suggest that the treatment is safe and well tolerated.
  • Eyal Banin, MD, PhD, at Hadassah Medical Center (Israel), provided an update on the Phase 1/2a OpRegen trial in dry AMD. OpRegen is a cell suspension composed of hESC-derived RPE cells that are injected into the subretinal space, where they are expected to integrate into areas of geographic atrophy (GA) and replace missing RPE cells. Initial results from the clinical trial indicate that vision has stabilized or improved in most patients.
  • Christelle Monville, PhD, University Evry (France), described the development, design, and preclinical validation of hESC-derived RPE cells on a scaffold of human amniotic membrane. It is hoped that these implants will eventually be used to treat dry AMD and retinitis pigementosa (RP).
  • Boris Stanzel, MD, Sulzbach Eye Clinic (Germany), shared the results from the preclinical validation of hESC-derived RPE cells in a model of dry AMD. This study looked at both the feasibility of worldwide transportation of cells for the graft and its functional and structural integration into the host retina.
  • Opsis Therapeutics (Madison, Wisconsin) is working to develop several different therapies based on induced pluripotent stem cells (iPSCs, stem cells derived from the blood and skin of humans). Lucas Chase, PhD, presented the design, development, and validation of these iPSC therapies in preclinical studies. The treatments include a scaffold to enhance cell survival, organization, and integration. The goal of Opsis Therapeutics is to treat AMD and inherited orphan conditions with these therapies.
  • Biju Thomas, PhD, at the University of Southern California, presented his work on a multilayer graft comprised of a hESC-derived RPE, an artificial Bruch’s membrane, and retinal organoids, which when implanted together can better recapitulate a real retina. Retinal organoids are a 3D cell culture comprised of retinal progenitor cells (RPCs) that can differentiate into rod photoreceptors. In addition to being important for peripheral vision, rod photoreceptors help to protect cone photoreceptors from degeneration. It is hoped that a multilayer graft comprised of several different cell types can regenerate all the layers of the retina and may be a better option for advanced retinal degenerative diseases.
  • The Regenerative Medicine Division of BOCO Silicon Valley is developing stem cells from the central nervous system (CNS-SC) to treat retinal diseases. Nobuko Uchida, PhD, described the development of CNS-SCs for retinal use and presented data from the Phase 1/2 clinical trial in dry AMD. The results of the trial show that the treatment was relatively safe and well tolerated, while also slowing the growth of geographic atrophy and producing modest gains in contrast sensitivity.
  • Michael Young, PhD, at Massachusetts Eye and Ear Infirmary (Boston), shared his work on the preclinical validation of retinal progenitor cells (RPCs) to treat blindness in animal models. On the basis of this research, ReNeuron is sponsoring an on-going Phase 1/2a clinical trial using RPCs to treat patients with RP. RPCs can differentiate into rod photoreceptors, thereby helping to stabilize cone photoreceptors and prevent progression of RP.
  • At the National Institutes of Health (NIH, Bethesda), Kapil Bharti, PhD, is developing patient-specific iPSCs to create 3D models of retinal diseases that can be used to understand disease progression and test potential therapies. Advanced differentiation techniques and 3D printing have been used to create a model of wet AMD. Future work will focus on using similar techniques to model other retinal diseases, such as dry AMD.
  • Magdalene Seiler, PhD, at the University of California, Irvine, presented her work on developing sheets from hESC-derived retina organoids. Preclinical animal models show that these sheets can be transplanted into damaged retinas and replace degenerated photoreceptors.
  • ProQR Therapeutics N.V. (Netherlands) focuses on using RNA oligonucleotides, small pieces of DNA or RNA that can modulate gene expression, to treat retinal diseases. Pete Adamson, PhD, discussed the development of QR-110 for the treatment of Leber congenital amaurosis caused by a mutation in the gene CEP290, which is the furthest along the development pathway. QR-110 has passed preclinical validation in retinal organoid models and ProQR Therapeutics N.V. has an ongoing Phase 1/2 clinical trial to study safety and dosing.
  • Maria Mirotsou, PhD, at the Astellas Institute for Regenerative Medicine (Massachusetts), described her work generating three different lines of photoreceptor-like cells from ESCs (two cell lines) and iPSCs (one cell line). The functional utility of these cell lines was tested by transplanting them into animal models that lack photoreceptors.
  • Henry Klassen, MD, PhD, University of California, Irvine, shared the results of his work on developing and validating retinal progenitor cells (stem cells that have nearly developed into photoreceptors) for the treatment of RP. He also shared some of the results of a recently completed Phase 1/2 clinical trial. The clinical trial showed that intraocular injection of RPCs was relatively safe and well tolerated, and there was a consistent elevation of visual acuity over baseline with a possible a dose response. His company jCyte has launched a Phase 2b study in 85 patients.
  • Jason Meyer, PhD, at Indiana University, presented his research on the differentiation of stem cells into retinal ganglion cells (RGCs) that can be used to model glaucoma and other diseases. It is hoped that markers can be identified from subsets of RGCs that will correlate to their ability to differentiate into specific cell types. This will aid in identifying specific RGCs that can treat specific diseases.
  • William Merigan, PhD, University of Rochester Medical Center (New York), reported his work on restoring vision using optogenetics, a technique that uses gene therapy to introduce light-sensitivity to retinal cells that survive after photoreceptors are lost to advanced retinal diseases. Research shows that optogenetic engineering can restore light sensitivity in animal models. Allergan and GenSight currently have clinical trials underway for optogenetic treatments for people with retinal diseases.
  • Jens Duebel, PhD, Institut de la Vision (France), presented on the transplantation of optogenetically engineered photoreceptors to restore visual function. Whole mature photoreceptors cannot be transplanted, so the work focuses on transplanting rod photoreceptor precursors that will then mature in the retina.

Gene Therapy Presentations

  • Shannon Boye, PhD, University of Florida, shared her work on intravitreal gene therapy delivery to treat LCA-1 that is caused by mutations in GUCY2D. Various animal studies have shown proof-of-concept that GUCY2D gene therapy could work and clinical trials are being designed. Dr. Boye is partnering with Genzyme to advance the treatment into the clinic.
  • Simon Petersen-Jones, DVet Med, PhD, DECVO, Michigan State University, described his work on large animal models of retinal diseases, in particular mutations in CNGB1 that cause progressive retinal atrophy (PRA) in dogs and RP in humans. Gene therapy has been highly successful in dogs and has provided data that will be used to design clinical trials.
  • Stargardt disease is usually caused by various mutations in the ABCA4 gene. However, only some disease-causing ABCA4 mutations have been identified. Rob Collin, PhD, Radboud University (Netherlands), is working to identify additional ABCA4 mutations that are responsible for Stargardt disease and has so far discovered six novel mutations. Work is now underway to develop antisense oligonucleotides that can be used to correct these mutations.
  • Hammerhead ribozymes (hhRz, RNA moecules) can target specific genes and decrease their expression. In dominant diseases, a mutated gene leads to the production of a toxic protein and needs to be “knocked down.” Jack Sullivan, MD, PhD, University at Buffalo-SUNY, is working to increase the efficacy and design of hhRz enzymes so that they are viable therapies for knocking down genes in autosomal dominant retinal diseases.
  • Clearside Biomedical (Gerogia) is focused on the administration of ocular treatments via suprachoroidal injection. The suprachoroidal space is between the sclera (white of the eye) and the choroid (layer of vasculature). As Glenn Noronha, PhD, explained, animal models have shown the feasibility of this approach for the delivery of triamcinolone acetonide, and Clearside Biomedical has completed a Phase 3 clinical trial for the treatment of macular edema associated with noninfectious uveitis (PEACHTREE). The results from PEACHTREE were positive, with treated patients experiencing increased visual acuity.
  • Yashodhan Chinchore, PhD, Harvard Medical School (Massachusetts), hypothesizes that energy metabolism can be targeted as a treatment for heterogenous diseases such as RP. Data shows that after rod photoreceptors degenerate, cone photoreceptors go through metabolic changes and eventually die because of glucose insufficiency. Glucose deprivation may be resolved by introducing genes responsible for increasing glucose concentrations, thereby preventing cone photoreceptors from dying.
  • 4D Molecular Therapeutics (California) specializes in creating large libraries of novel adeno-associated vectors (human-engineered viruses) to deliver gene therapies. These vectors can be shared (licensed) to meet the specific needs and disease targets of gene therapy developers. David Kirn, MD, shared the process of optimizing and validating vector libraries for retinal delivery.
  • Ellery Mangas, senior director of regulatory affairs, described how AGTC (Florida) is working on the intravitreal delivery of an engineered AAV2 (AAV2tYF) vector for the treatment of X-linked retinoschisis (XLRS). Preclinical work in animal models shows that this AAV2tYF vector delivers a higher amount of gene therapy to the retina and induces the same amount of inflammation as the normal AAV2 vector.
  • Francine Behar-Cohen, MD, PhD, at Eyevensys (France) is developing a non-viral gene therapy (EYS606) for the treatment of noninfectious uveitis. EYS606 is delivered using electro-transfection in which a pulse of electricity is used to open pores in cell membranes for gene delivery. Preliminary data from an ongoing Phase 1/2 clinical trial suggests that it is quick, easy, and relatively painless to deliver EYS606, and the treatment is relatively safe.
  • Huber Vasconcelos Jr, MD, Paulista Institute of Studies and Research in Ophthalmology (Brazil), shared surgical videos that illustrated his tips and techniques to optimize retinal gene therapy. Intraoperative optical coherence tomography (iOCT) can help the surgeon visualize the entire treatment application process, which can increase therapeutic efficacy.
  • Katherine High, MD, president and head of research and development at Spark Therapeutics (Philadelphia), gave a keynote speech on the development of LUXTURNAÔ and the clinical trial results that led to it becoming the first FDA-approved gene therapy for a genetic disease or the eye. LUXTURNA is a one-time gene therapy for individuals with LCA or RP due to mutations in both copies of the RPE65 gene. As an accompaniment to this presentation, Jason Comander, MD, PhD, Massachusetts Eye and Ear Infirmary, showed a compelling video testimonial from a patient treated with LUXTURNA.
  • Kari Branham, assistant research Scientist and director of ophthalmic genetic counseling at the University of Michigan’s Kellogg Eye Center, shared tips and techniques on identifying patients with the appropriate genetics that would make them suitable candidates for gene therapy trials.
  • Jason Comander, MD, PhD, Massachusetts Eye and Ear Infirmary, discussed his work on using functional assays to clarify the importance of variants of unknown significance in genetic diseases. In any gene, there are many variants of unknown significance that may or may not play a role in disease development. Determining their value is important to understanding which patients can be successfully treated by gene therapy.
  • Thomas Ciulla, MD, MBA, Spark Therapeutics (Philadelphia), shared data from the three-year endpoint of the LUXTURNA clinical trial that illustrated the durability of treatment. Three years after treatment, patients continued to improve in the luminance mobility course, a method to measure functional vision, and had stable visual acuity.
  • José-Alain Sahel, MD, Institut de la Vision (France) and University of Pittsburgh, reported on the results of the Phase 1b/2a and Phase 3 (REVERSE) trials of gene therapy to treat Leber’s hereditary optic neuropathy (LHON) that have been sponsored by GenSight Biologics. The Phase 1b/2a trial is in its extension phase to look at long term safety and the 2.5-year results show that the gene therapy has excellent systemic safety and good ocular safety. While there are three phase 3 trials currently underway, only the results from the REVERSE trial were shared. Patients experienced visual improvement in both eyes (treated and untreated) and there were modest structural changes indicating a positive treatment effect.
  • Byron Lam, MD provided an overview of the clinical trials in gene therapy for LHON and choroideremia that have involved the Bascom Palmer Eye Institute at the University of Miami. For LHON, Bascom Palmer has participated in both a National Eye Institute (NEI)-funded Phase 1 clinical trial and the REVERSE clinical trial. In both trials, there have been slight improvements in visual acuity and both therapies have been relatively safe and well tolerated. Nightstar Therapeutics funded a Phase 1/2 clinical trial for choroideremia that has resulted in some patients, so called hyper-responders, having dramatic improvement one month after treatment. Additional clinical trials are on-going.
  • Mark Pennesi, MD, PhD, Oregon Health & Science University, reviewed the preliminary safety results from a Phase 1/2a study of an intravitreal gene therapy for To date, 27 patients have been treated in the AGTC-sponsored clinical trial and only the safety results can be reported. Efficacy data for the clinical trial will be reported later.
  • Paul Sieving, MD, PhD, presented an update on the NEI-funded Phase 1/2a trial of gene transfer (Bethesda) to treat XLRS. Nine patients have been treated so far and the safety profile of the gene therapy looks good. There were also preliminary signs of a biological response in at least one patient.
  • Isabelle Audo, MD, PhD, Institut de la Vision (France), discussed the two Phase 1/2a trials being conducted by Sanofi, one on Stargardt disease and the other on Usher 1B syndrome. In total, 25 patients have been treated in the Stargardt trial and 9 patients in the Usher trial. For both treatments, the safety profiles are similar to that of any intraocular surgery and no significant systemic reactions were observed. Both treatments also prevented further visual acuity loss.
  • Allen Ho, MD, FACS, Wills Eye Institute (Philadelphia), shared his tips and techniques to optimize the subretinal delivery of the gene therapy RGX-314 in wet AMD. Blocking vascular endothelial growth factor (VEGF) has been shown to be effective in wet AMD treatment, so REGENXBIO developed RGX-314 that causes cells to create their own anti-VEGF proteins. Topline results from the Phase 1 study are expected in late 2018.