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™ Ophthalmology specialty topic page includes the most recent clinical care news related to the development of cell therapies, gene therapies, and engineered and regenerative medicines for disorders and diseases of the eye. It also contains video interviews with key opinion leaders in the field of ophthalmology discussing related FDA actions, clinical guideline updates, and clinical trial findings in the field of gene and cell therapy for ophthalmic conditions.

Videos

According to Henry Kaplan, MD, University of Louisville School of Medicine, "One has to recognize that there are multiple approaches like gene therapy, neuroprotection, stem cell transplantation, and pharmacologic manipulation of other genes really holds the greatest benefit in terms of trying to reverse the inevitable loss of vision."

Henry Kaplan from University of Louisville School of Medicine: Combatting Retinal Degeneration with Glucose

Articles

Gene therapy with the CRISPR/Cas9 system corrects mutations identified with patient-specific models that use stem cells generated from skin.

Genetics-Based Advances in Retinitis Pigmentosa Research

Study results show that transplanted human retinal stem cells rescue photoreceptors in rabbit retinas for 8 months.

Milestone in Stem Cell Transplant Therapy for Advanced Age-Related Macular Degeneration

In Episode 5 of ImmunoLogic, Michael T. Lotze, MD, discussed the evolution and future of tumor infiltrating lymphocyte (TIL) therapies.

ImmunoLogic, Episode 5: "Tumor Infiltrating Lymphocytes" With Michael T. Lotze, MD

We're excited to introduce another episode of the 

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is often joined by cohost 

 a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

a professor of surgery, immunology, and bioengineering at the University of Pittsburgh, about his work on tumor infiltrating lymphoctye (TIL) therapy. Fraietta and Lotze covered topics including the history of TIL research, the potential of TIL therapy in different tumor types, Lotze and his colleagues' new reciprocal learning model hypothesis, and concluded with some philosophical reflections on cancer research.

 is tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. This podcast is an essential resource for those driving the future of immunotherapy.

Interested in co-hosting an episode or being a guest? Have feedback to share? 

If you'd like to get in touch to talk about the show, contact our editorial director, Matt Hoffman: 

Podcasts

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with CAR-T.

 ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances" With Caroline Diorio, MD, FRCPC, FAAP

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is joined by cohost 

an attending physician at the Cancer Center at Children's Hospital of Philadelphia, about her research into inflammatory toxicities in cell therapy. Diorio, Fraietta, and Minehart covered topics including predicting and managing toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), the need for rigorous research to understand the underlying biology of these toxicities, the importance of transparency in manufacturing processes, and the potential for decoupling potency from toxicity.

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with cell therapy.

ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances: Navigating Toxicities in Immunotherapies" With Caroline Diorio, MD, FRCPC, FAAP

In Episode 3 of ImmunoLogic, Marcela Maus, MD, PhD, discussed her research on CAR-T for treating glioblastoma.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

the director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center, about her research into the use of chimeric antigen receptor T-cell (CAR-T) therapy to treat glioblastoma. Maus, Fraietta, and Minehart covered topics including challenges and insights from early clinical trials, innovations and clinical results, antigen expression and the possibility of readministration, as well as the autologous versus allogeneic debate.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T-Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

In Episode 2 of ImmunoLogic, Bruce Levine, PhD, discussed the current the risk-benefit-ratio for CAR-T therapy.

ImmunoLogic, Episode 2: "Charting New Frontiers in CAR T-Cell Safety" With Bruce Levine, PhD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

 the Barbara and Edward Netter Professor in Cancer Gene Therapy at the Perelman School of Medicine at the University of Pennsylvania, about the black box warnings for secondary malignancies that were issued by the FDA with regard to the autologous chimeric antigen receptor T-cell (CAR-T) therapies approved by the agency, and the implications of the findings that informed these warnings for the risk-benefit ratio of these therapies. Levine, Fraietta, and Minehart covered topics including risk and informed consent, genetic modification as it relates to safety, epitope spreading and T-cell stimulation, and the importance of the National Institutes of Health (NIH) to CAR T-cell research.

In Episode 1 of ImmunoLogic, Stephen J. Schuster, MD, discussed the potential of treating lymphoma without chemotherapy.

ImmunoLogic, Episode 1: "Chemo-Free Lymphoma? Seriously?" With Stephen J. Schuster, MD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

, the director of the Lymphoma Program at Penn Medicine, about the changing role of chemotherapy in lymphoma treatment, and the potential for its elimination. Schuster covered topics including trials for chimeric antigen receptor T-cell (CAR-T) therapy without lymphodepletion, using AI to predict CAR-T treatment outcomes, the importance of T-cell fitness, and the role of persistence in CAR-T success.

Joseph Fraietta, PhD, previews his new podcast, ImmunoLogic

ImmunoLogic Episode 0

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions.

In this short preview episode, Fraietta outlines the podcast’s mission to scrutinize the critical milestones shaping immunotherapy today and discuss how episodes will analyze the journey from bench to bedside—focusing on the real-world implementation of clinical data and the impact of regulatory achievements on patient outcomes. Topics will include discussions on chimeric antigen receptor (CAR) T-cell therapies, tumor-infiltrating lymphocyte (TIL)-based approaches, antibody-driven treatments, and the latest advances in gene editing technologies such as CRISPR, with a goal of expanding the conversation outside of the field of oncology.

 will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. With its first full episode launching in early 2025, this podcast promises to be an essential resource for those driving the future of immunotherapy.

Hosted by Joseph Fraietta, PhD, ImmunoLogic will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility.

CGTLive® Presents: ImmunoLogic, A Video Podcast With Joseph Fraietta, PhD

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – July 30, 2025

Review top news and interview highlights from the week ending July 25, 2025.

CGTLive®’s Weekly Rewind – July 25, 2025

Ocugen initiates pivotal confirmatory trial for OCU410ST, its second modifier gene therapy candidate, in patients with Stargardt disease.

First Patient Dosed in Phase 2/3 GARDian3 Trial of OCU410ST for Stargardt Disease

Around the Helix: Cell and Gene Therapy Company Updates – July 23, 2025

Review top news and interview highlights from the week ending July 18, 2025.

CGTLive®’s Weekly Rewind – July 18, 2025

The chief scientific officer and head of research, development, and Medical at Ocugen, also discussed future plans for the gene therapy, which is now in a phase 3 study.

Arun Upadhyay, PhD, on Results from IRD Gene Therapy OCU400’s Phase 1/2 Trial

“I would like to highlight that currently we are enrolling patients in our OCU400 phase 3 study... It is for a broader indication, and this is the first of its own kind of trial in this space. No other company to our knowledge is running a broader RP designation trial.”

Currently, substantial unmet need remains for patients with inherited retinal diseases (IRDs) such as retinitis pigmentosa (RP). Because mutations in a wide range of genes can cause IRDs like RP, developing targeted gene therapy products with the traditional “1 therapy for 1 gene” approach is impractical. As such, Ocugen has decided upon pursuing a gene-agnostic approach to treating IRDs with its Modifier Gene Therapy Platform. OCU400, a gene therapy product based on this platform, is currently being evaluated in a phase 1/2 clinical trial (NCT05203939) for the treatment of RP and Leber congenital amaurosis (LCA), as well as a more recently-initiated phase 3 clinical trial (liMeliGhT; NCT06388200), which dosed its first patient 

 of this year. Notably, data from the earlier phase 1/2 trial was recently presented at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain.

 spoke with Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to learn more about the updated data. Upadhyay pointed out that across 18 patients treated in the study, OCU400 was generally safe and well-tolerated. In terms of efficacy, he emphasized that close to 60% of the intent-to-treat population responded to OCU400 with regard to a luminance dependent navigation assessment, which constitutes a primary end point in the phase 3 trial. Upadhyay also noted that OCU400 has received orphan drug designation from both the FDA and the European Medicines Agency for RP and LCA, and that it has received regenerative medicines advanced therapy designation from the FDA, as well as an expanded access protocol from the FDA in RP.

REFERENCE
1. Ocugen, Inc. Announces First Patient Dosed in Phase 3 liMeliGhT Clinical Trial for OCU400—First Gene Therapy in Phase 3 with a Broad Retinitis Pigmentosa Indication. June 20, 2024. Accessed September 30, 2024. https://www.globenewswire.com/news-release/2024/06/20/2901513/0/en/Ocugen-Inc-Announces-First-Patient-Dosed-in-Phase-3-liMeliGhT-Clinical-Trial-for-OCU400-First-Gene-Therapy-in-Phase-3-with-a-Broad-Retinitis-Pigmentosa-Indication.html

The chief scientific officer and head of research, development, and Medical at Ocugen, discussed OCU400, the company’s gene-agnostic gene therapy for IRDs.

Arun Upadhyay, PhD, on the Potential of Gene Therapy in Inherited Retinal Disease

“Our approach is more gene-agnostic in nature, which not only enhances the function of the photoreceptor, but also helps with preserving the surviving retinal cells through cellular and molecular homeostasis.”

Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) that affects more than 100,000 people in the United States. Symptoms of RP include night blindness, a gradual loss of peripheral vision, and potentially blindness in the long-run. The condition is associated with over 100 genes. Although, currently the only targeted FDA-approved product for RP can only be used for the treatment of patients with a mutation in the 

 gene; this represents only around 2% of patients with RP. As such, great unmet need remains for the overall patient population with RP. Because of the wide range of genes implicated in the condition, it is unlikely to be feasible for gene therapy approaches targeted at each specific gene to be developed and commercialized in a reasonable amount of time. In order to work around this issue, Ocugen has developed its Modifier Gene Therapy Platform, which may allow for a gene-agnostic approach to treating IRDs. One of the company’s gene therapy products based on this platform, OCU400, recently entered a phase 3 clinical trial (liMeliGhT; NCT06388200). The first patient in liMeliGhT 

 of this year. Furthermore, findings from a phase 1/2 clinical trial (NCT05203939) in RP and Leber congenital amaurosis were recently presented at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain.

 reached out to Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to learn more about the company’s approach. Upadhyay described the current landscape of care for RP and the unmet needs that remain. He then spoke about how OCU400 works and the design of the new phase 3 trial.

REFERENCES
1. Ocugen, Inc. Announces First Patient Dosed in Phase 3liMeliGhT Clinical Trial for OCU400—First Gene Therapy in Phase 3 with a Broad Retinitis Pigmentosa Indication. June 20, 2024. Accessed September 25, 2024. https://www.globenewswire.com/news-release/2024/06/20/2901513/0/en/Ocugen-Inc-Announces-First-Patient-Dosed-in-Phase-3-liMeliGhT-Clinical-Trial-for-OCU400-First-Gene-Therapy-in-Phase-3-with-a-Broad-Retinitis-Pigmentosa-Indication.html

The chief technology officer at GenSight Biologics discussed using Verdot’s FlexiPro system to produce Lumevoq gene therapy. 

Scott Jeffers, PhD, on The Importance of Precise Reproducibility of AAVs 

“The purity of the viral vector is super important. It needs to be ultra pure and ready to go to be injected into people, in order to be safe and effective and potent, and to make sure that that it's doing what it's supposed to do. But the purification process needs to also be controlled really well. We need it to be reproducible. We need to do it over and over again. It needs to do the same thing every time we do it. We need to know that it's doing it in the same way, as well as being able to monitor that.”

Manufacturing adeno-associated virus (AAV) vector-based gene therapy is a complex and expensive process that needs to be precisely reproducible and controlled. New platforms and technologies are constantly being pursued to help streamline and improve gene therapy manufacturing. GenSight Biologics recently turned to Verdot Biotechnologies’ FlexiPro system to improve the purification of its gene therapy product, Lumevoq (GS010).

Lumevoq is being evaluated in the phase 3 REFLECT clinical trial (NCT03293524) in participants with Leber hereditary optic neuropath. GenSight recently presented long-term follow-up data from REFLECT that demonstrated sustained improvements in best corrected visual acuity.

Scott Jeffers, PhD, chief technology officer, GenSight, also gave a talk about how the company has improved viral purification during AAV manufacturing with the FlexiPro system at 

the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting

, held May 7 to 10, 2024, in Baltimore, Maryland.

 spoke with Jeffers to learn more about the changes in manufacturing. He emphasized the importance of having a system that can yield accurate and precise reproducibility of its products.

1. GenSight Biologics confirms sustained efficacy and safety of bilateral LUMEVOQ® injections four years after one-time administration. News release. GenSight Biologics. March 20, 2024. https://www.gensight-biologics.com/2024/03/20/gensight-biologics-confirms-sustained-efficacy-and-safety-of-bilateral-lumevoq-injections-four-years-after-one-time-administration/
2. Increased Reproducibility in a Critical Downstream Processing Step Allows for Speed to Commercialization of Gene Therapy Product to Treat Leber's Hereditary Optic Neuropathy (LHON). Presented at: Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #1031

The chief medical officer and head of translational research at Ring Therapeutics discussed research presented at ASGCT 2024. 

Chris Wright, MD, PhD, on Annelloviruses, a Potential Alternative to AAV for Gene Therapy 

“We were looking in the body for different viruses that are persisting there, but not causing any problems. So, we did find a number of viruses, the anelloviruses. Anelloviruses actually make up about 80% of all the viruses in a person's body. And it turns out that that they've been there throughout all of the person's life, pretty much shortly after birth. So, they persist for a long period of time, and they don't appear to cause any problems, they don't induce an immune reaction, and they don't seem to have any associations with diseases. So, we thought that could be a great virus to use to try to deliver gene therapy, because it should be a safe approach.”

Ring Therapeutics is developing anellovectors as potential alternatives to adeno-associated virus (AAV) gene therapies. AAV therapies, although currently the standard for gene therapies and an approved modality, have inherent challenges, including immune responses and lack of redosability. Anelloviruses, found naturally in the human body, have potential to address these challenges for gene therapies.

Ring presented data from multiple studies on anelloviruses at 

, held May 7 to 10, 2024, in Baltimore, Maryland. 

spoke with Chris Wright, MD, PhD, chief medical officer and head, translational research, Ring Therapeutics, to learn more about anelloviruses and the data presented at ASGCT. He overviewed the outstanding issues with AAV therapies and how anelloviruses may address these challenges. He also outlined the different research presented at the meeting, including demonstrating a large payload with anelloviruses, demonstrating transduction in the eye in nonhuman primates, and demonstrating redosability without issue.

Bounoutas GS, Pozsgai R, Gold I, et al. Anellovectors, a Gene Delivery Platform Based on Commensal Human Anelloviruses, Have the Potential to Evade the Immune System and Deliver DNA Payloads to a Broad Range of Tissues in a Redosable Manner. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #203

Chris Wright, MD, PhD, on Anelloviruses, a Potential Alternative to AAV for Gene Therapy 

The clinical professor of neurology and pediatrics at Keck School of Medicine of USC also discussed current strategies with gene therapy administration. 

Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth 

“I think gene therapies in general are going to grow. If we look at the approvals that have happened, at first it was just Luxturna and then maybe onasemnogene... and then they just started taking off. I mean, last year, there were several that were approved. I'm listening to not just in neuromuscular, but also in epilepsy, neurodevelopmental disorders, all of these therapies that are coming out in the hematology world, in the leukodystrophy world. And I think it's going to be a very different experience as a pediatric medicine provider in the next 10 years. It's exciting. It's scary. I don't know how our systems are going to be able to handle all of these kinds of treatments. But it's always a learning experience."

As gene therapies become more common and grow in prevalence in the clinical space, it is important to strategize their administered in the clinic and examine current strategies for logistics of delivering gene therapies.Coordinating interdepartmental collaboration in centers delivering these therapies is also paramount, as well as ensuring informed consent.

Leigh Ramos-Platt, MD, Medical Director, Muscular Dystrophy Association Neuromuscular Clinic and attending physician, Division of Neurology, Children’s Hospital Los Angeles, and Clinical Professor of Neurology and Pediatrics, Keck School of Medicine, University of Southern California (USC), gave a talk around this topic at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 3-6, in Orlando, Florida.

® spoke with Ramos-Platt to learn more about some takeaways from the talk, including communication between parties and strategizing care as the most salient points. She also shared her excitement for the gene therapy space in general, which she has seen grow since her time in the field and expects to continue to grow in the near future.

Ramos-Platt L. DMD Gene Therapy Day Of: Institutional and Patient/Family Readiness- When We Were Not a Trial Site. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Orlando, FL.

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison shared highlights of discussion. 

Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary 

“I shared the kickoff plenary of the ISCT, which is branded as La Présidentielle. The whole idea is to bring in leaders of sister societies to come and speak to us about what's the mission and vision, for us to have an understanding of the broader ecosystem of cell and gene therapy, especially for knowledge-based societies like ours... there is sort of a common theme in Europe, the UK, the US, that there are so called deserts where there are commercially approved products but eligible patients, especially if they live in rural areas and are of modest means, even though they’re eligible to receive the treatment, don't receive it. How do you tackle that?”

The presidential plenary of the International Society for Cell and Gene Therapy (ISCT) 2024 Meeting, held in Vancouver, Canada, from May 29 - June 1, brought together leaders of sister scholarly societies, including Anna Sureda, MD, PhD, president of European Society for Blood and Marrow Transplantation; Amander Clark, PhD, president, International Society for Stem Cell Research; and Corey Cutler, MD, MPH, FRCP(C), president, American Society for Transplantation and Cellular Therapy, with Jacques Galipeau, MD, president, ISCT, chairing the session, to discuss the current state of development with cell and gene therapies and challenges that the process faces, within each country and internationally.

 spoke with Galipeau to learn more about the plenary and the highlights discussed between the speakers. He shared the different perspectives that each speaker brought to the discussion, with Sureda speaking about the state of development in Spain with the European Medicines Agency. One challenge, Galipeau noted, was relevant regardless of country, and that is tackling the problem of “deserts” in the treatment landscape.

Galipeau J, Sureda A, Clark A, Cutler C. La présidentielle. Presented at: ISCT 2024 Meeting, held in Vancouver, Canada, from May 29 – June 1.

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison shared highlights from the discussion. 

The associate professor of otolaryngology from Harvard Medical School also shared his excitement for the positive data on AAV1-hOTOF.

Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials 

“This clearly shows how this kind of collaborative approach can really advance medical discovery much more rapidly, and in the end will help everybody… So that I think is one of the very important messages. We need to have this kind of collaboration, we can do more… to find out where the patient population comes from, to treat more patients, to do more trials, and then we can have a new treatment out quicker.”

AAV1-hOTOF gene therapy yielded significant, clinically meaningful improvements in hearing in 5 of 6 children with autosomal recessive deafness 9 (DFNB9) caused by mutations of the OTOF gene. The clinical trial assessing AAV1-hOTOF is being conducted in collaboration with investigators from Mass Eye and Ear at the Eye & ENT Hospital of Fudan University in Shanghai, China.

Investigators observed no serious adverse events or dose-limiting toxicities. The improvements included hearing recovery, improvements in speech recovery, and significant reductions in the average auditory brainstem response. One participant did not have a response to AAV1-hOTOF, and the investigators theorized that the nonresponse may have been due to their higher concentration of neutralizing antibodies at baseline, or, alternatively, a possible leakage of the AAV1-hOTOF solution from the round window membrane during or after surgery.

 spoke with study investigator Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, to learn more about the international trial and the collaboration that allowed it and enriched it. He shared his excitement for the positive data and adding to the body of supporting literature for gene therapy in general.

Lu J, Wang H, Cheng X, et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. 

. Published online January 24, 2024. doi: 10.1016/S0140-6736(23)02874-X

The cofounder, chairman, and CEO of Kriya Therapeutics discussed the company’s goal of bringing gene therapy to a much broader population of patients.

Shankar Ramaswamy, MD, on Bringing Gene Therapy to Common Diseases

“The technology has really matured to a point where we can take that next leap as a field to bring gene therapies into a broader universe of diseases. I think we as a field need to figure out how we can scale the technology, how we can bring down the cost, and how we can improve throughput and quality of the products that we engineer and manufacture. But those are solvable challenges.”

Gene therapy, particularly adeno-associated virus vector-based gene therapy, first gained its foothold in the field of medicine by targeting relatively rare inherited disorders like Duchenne muscular dystrophy and hemophilia A, both of which are now among the indications for the 6 FDA-approved AAV vector-based gene therapies. Indeed, this trend has continued, with many companies and academic institutions continuing to pursue the development of AAV vector-based gene therapies for rare and even ultrarare genetic disorders. Because of the high cost and lengthy and complex manufacturing process for gene therapy products, targeting smaller patient populations for both clinical trials and commercial products is in some ways a good fit for the modality. That said, gene therapy may have the potential to treat much more common diseases, as well. One company currently seeking to bring AAV vector-based gene therapy to common diseases is Kriya Therapeutics. Kriya gave 6 presentations regarding their work on this endeavor at 

, held May 7 to 10, 2024, in Baltimore, MD.

® sat down with Shankar Ramaswamy, MD, the cofounder, chairman, and CEO of Kriya Therapeutics, to learn more about the company’s efforts. Ramaswamy explained that gene therapy has significant potential to address unmet needs for relatively common diseases like type 1 diabetes and geographic atrophy, but that bringing gene therapy to such indications will require overcoming challenges such as scaling manufacturing, reducing costs, and characterizing products. He noted that Kriya is currently working on technologies and methods to address these concerns, and gave his view that gene therapy is on the precipice of reaching much broader use in clinical practice.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

The associate professor of otolaryngology from Harvard Medical School discussed further research being pursued with AAV1-hOTOF gene therapy. 

Zheng-Yi Chen, DPhil, on Looking Deeper Into Effects of Gene Therapy on OTOF Deafness 

“The one major limitation of cochlear implants is music appreciation, which is completely different than what we experience. So, we're doing a study to see whether they have a better sense of music appreciation, they can hear the pitch, frequency and everything embedded in the music, because we know how important that is to a person.”

Five out of 6 children with autosomal recessive deafness 9 (DFNB9) caused by mutations of the OTOF gene experienced significant, clinically meaningful improvements in hearing after receiving AAV1-hOTOF gene therapy. The participants were treated as part of a clinical trial conducted in collaboration with investigators from Mass Eye and Ear at the Eye & ENT Hospital of Fudan University in Shanghai, China.

The participants had hearing recovery, improvements in speech recovery, and significant reductions in the average auditory brainstem response. In the 1 nonresponding participant, the investigators theorized that the nonresponse may have been due to their higher concentration of neutralizing antibodies at baseline, or, alternatively, a possible leakage of the AAV1-hOTOF solution from the round window membrane during or after surgery. There were no serious adverse events or dose-limiting toxicities.

spoke with study investigator Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, to learn more about the progress of the trial. He also shared some other research efforts ongoing with AAV1-hOTOF gene therapy, including effects on music appreciation.

Khanani discussed also discussed the latest results announced from the phase 2 portion of the PRISM study.

Arshad Khanani, MD, on Comparing Wet AMD Gene Therapy 4D-150 to Aflibercept in a Randomized Clinical Trial

“I'm thrilled to see these results in terms of efficacy and safety. Because of these positive results, the program is moving forward into the phase 3 pivotal stage.”

Currently, the standard of care (SOC) treatment option for patients with wet age-related macular degeneration (AMD) involves repeated injections of an antivascular endothelial growth factor (VEGF) drug such as aflibercept. For some patients, these injections are needed about every 2 months in order to maintain stability of vision, but because of the high burden of receiving this treatment, many patients do not actually receive injections with ideal frequency in the real-world setting. As such, many patients with wet AMD tend to experience additional loss of vision over time. 4D Molecular Therapeutics (4DMT) is currently developing 4D-150, an investigational dual-mechanism gene therapy, with the intention of overcoming this limitation of the SOC treatment approach. 4D-150 is intended to provide patients’ cells with the ability to consistently produce both aflibercept and an interference RNA for VEGF-C after a single, 1-time injection. The gene therapy is currently being evaluated in the phase 1/2 PRISM clinical trial (NCT05197270). Notably, positive interim results from the randomized-control phase 2 portion of PRISM, which included patients with particularly high-need for antiVEGF injections,were recently announced by 4DMT in February of this year.

® sat down with lead principal investigator Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, to learn more about the latest findings. Khanani provided some background information about 4D-150 and the PRISM study, and then went over the new data in detail. He emphasized that patients treated with 4D-150 showed much less fluctuation in central subfield thickness (CST) compared to patients treated with aflibercept in the control arm. Khanani also went over the continued promising safety outcomes seen with the gene therapy in PRISM, noting that there were no serious adverse events related to 4D-150 observed.

REFERENCES
1. 4DMT presents positive interim data from randomized phase 2 PRISM clinical trial of intravitreal 4D-150 demonstrating favorable tolerability & clinical activity in wet AMD. News release. 4D Molecular Therapeutics. February 3 ,2024. Accessed March 11, 2024. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-presents-positive-interim-data-randomized-phase-2-prism


The assistant professor in the department of pediatrics at the University of Florida College of Medicine discussed also discussed the latest results announced from the phase 2 portion of the PRISM study.

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