Vyznova (neltependocel) / Aurion Biotech - LARVOL DELTA

Safety and Efficacy of Mature Cultured Corneal Endothelial Cell Therapy (Vyznova) in Eyes With Declining Long-term Efficacy After Prototype Cell Transplantation. (PubMed, Cornea) - "Administration of Vyznova was safe and demonstrated favorable clinical outcomes in eyes with declining long-term efficacy after initial treatment with prototype CECs. These findings support the feasibility of Vyznova as a treatment strategy for corneal endothelial failure in patients previously treated with cultured CECs."

First-in-human • Journal • Ocular Inflammation • Ophthalmology • Transplant Rejection • Transplantation • Uveitis

Cystoid Macular Edema After Cultured Human Corneal Endothelial Cell Injection: Frequency, Associated Factors, and Visual Outcomes. (PubMed, Am J Ophthalmol) - "CME was detected postoperatively in approximately one-quarter of eyes after cHCEC injection therapy and was associated with preoperative prostaglandin analog use. Most cases were detected during the early postoperative period and resolved with treatment without adversely affecting 6-month visual outcomes. Careful perioperative management of prostaglandin analogs and routine postoperative optical coherence tomography may facilitate early detection and management of CME."

Journal • Glaucoma • Macular Edema • Ophthalmology

Endothelial Cell Therapy for Post-Keratoplasty Corneal Endothelial Failure. (PubMed, Ophthalmology) - No abstract available

Journal • Ophthalmology • Transplantation

Designing a Large-Scale Cell Therapy: Clinical Validation and Early Commercialization of Corneal Endothelial Cell Therapy (ASGCT 2026) - "Vyznova, or cultured human corneal endothelial cell (cHCEC) therapy, is the first approved cell therapy for the treatment of corneal dystrophy, a blinding eye disease affecting millions worldwide...With approval in Japan and RMAT/BTD designations, in the US, this therapeutic is positioned to become a large-scale cell therapy that solves the global donor cornea shortage with the potential to help eliminate a leading cause of corneal blindness that affects millions worldwide. Figure Legend Figure 1: Meta-analysis of functional and anatomical improvements in corneal endothelial dysfunctionFigure 2: Efficacy of cHCEC therapy in varying stages of corneal endothelial disease"

Clinical • Ophthalmology

Early Clinical Outcomes of Cultured Human Corneal Endothelial Cell Injection (Vyznova) for Bullous Keratopathy (ARVO 2026) - "Conclusions Vyznova therapy using cultured human corneal endothelial cells demonstrated favorable safety and efficacy across various etiologies of bullous keratopathy. Nevertheless, postoperative complications require careful monitoring and management."

Clinical data • Glaucoma • Keratitis • Macular Edema • Ocular Infections • Ocular Inflammation • Ophthalmology

Cultured Human Corneal Endothelial Cell Injection (Vyznova) in Eyes with Extremely Low Intraocular Pressure After Glaucoma Surgery: Case Reports. (PubMed, Cornea) - "These cases highlight that cHCEC therapy may be a safe and effective treatment for BK in eyes with extremely low IOP after glaucoma surgery, representing a promising alternative when conventional endothelial keratoplasty carries a high risk."

Journal • Glaucoma • Ophthalmology • Transplantation

The "Polish Sign": A Novel Intraoperative Visual Indicator During Descemet Membrane Polishing in Cultured Human Corneal Endothelial Cell Injection Therapy. (PubMed, Cornea) - "The polish sign provides a simple, real-time indicator that enables safe and consistent DM polishing while minimizing the risk of DM injury. Although its visibility may decrease in eyes with dense stromal opacity, adjusting illumination can enhance recognition, suggesting that the sign may have relevance across various endothelial cell-based therapies."

Journal • Infectious Disease • Ophthalmology • Transplantation

AURN001 Efficacy in Participants With Corneal Edema Secondary to Corneal Endothelial Dysfunction (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Aurion Biotech | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology

A Modified Long Corneal Tunnel Technique for Intracameral Injection in Cultured Human Corneal Endothelial Cell Therapy (Vyznova): A Preliminary Technical Report. (PubMed, Cornea) - "This preliminary single-surgeon case series suggests that the long corneal tunnel technique may facilitate macroscopically leak-free wound closure during cHCEC injection. Although encouraging, these findings are limited by subjective leak assessment and small sample size. Larger multicenter studies incorporating objective leak quantification are required to determine reproducibility and comparative performance."

Journal • Astigmatism • Ophthalmology

AURN001 Efficacy in Participants With Corneal Edema Secondary to Corneal Endothelial Dysfunction (clinicaltrials.gov) - P3 | N=120 | Not yet recruiting | Sponsor: Aurion Biotech

New P3 trial • Ophthalmology

CLARA: A Phase 1/2 Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1) (clinicaltrials.gov) - P1/2 | N=97 | Completed | Sponsor: Aurion Biotech | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Apr 2025

Trial completion • Trial completion date

Aurion Biotech Achieves All Primary, Secondary, and Exploratory Endpoints in AURN001 Phase 1/2 CLARA Trial at 12 Months (Businesswire) - "The findings were presented at Cornea Day during the American Academy of Ophthalmology (AAO) meeting....At 12 months, 65% of subjects in the high-dose AURN001 group vs. 0% of the Y-27632 group achieved a ≥15-letter best corrected visual acuity (BCVA) gain (p<0.0001). Also, in the high-dose group, the mean change in BCVA from baseline was 12.5 letters, mean reduction in central corneal thickness (CCT) was 23.2 µm....Data strongly supports advancing high dose AURN001 regenerative cell therapy for patients with corneal endothelial disease to pivotal Phase 3 trial in H1 2026."

New P3 trial • P1/2 data • Ophthalmology

Early Clinical Outcomes of Cultured Human Corneal Endothelial Cell Injection (Vyznova) for Bullous Keratopathy: Initial Clinical Experience. (PubMed, Cornea) - "Vyznova therapy seems to be effective in restoring corneal clarity in patients with BK. This real-world experience underscores the feasibility of implementing cHCEC injections in institutions beyond the developer sites. Careful intraoperative management is necessary to avoid complications, such as detachment of Descemet membrane."

Clinical data • Journal • Ophthalmology • Transplantation

Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval. (PubMed, Regen Ther) - "The period for Luxturna Injection® (Novartis Pharma), categorized as a pharmaceutical product, to be included was 65 days, which was within the standard administrative processing time for pharmaceutical products, (i.e., 60 days or less, yet no later than 90 days), while the elapsed periods for Nepic® and Ocural® (Japan Tissue Engineering), Sakracy® (CynosBio), and Vyznova® (Aurion Biotech Japan), which are categorized as medical devices, were 74, 173, 224, and 534 days, respectively. Regenerative medical products categorized as medical devices are required to undergo a review process conducted by the Technical Committee for Insurance Materials on Medical Devices of the Japanese Central Social Insurance Medical Council. Our findings suggest that both manufacturers and regulatory authorities need to revise the Technical Committee's strategy from the aspect of putting regenerative medical products into practical clinical use in Japan."

Journal • Reimbursement • US reimbursement • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Six-Month Interim Data Analysis of CLARA; A Phase 1/2 Prospective, Clinical Trial of Investigational Human Corneal Endothelial Cell Therapy for Corneal Edema Secondary to Corneal Endothelial Dysfunction. (ARVO 2025) - "Purpose The primary objective of the CLARA trial is to evaluate the efficacy of a single administered dose of varied concentrations of human corneal endothelial cells (CECs) in combination with Y-27632 Rho-Kinase Inhibitor (i.e., AURN001) compared to CECs alone, and Y-27632 alone in subjects with corneal edema...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P1/2 data • Ophthalmology

Study of Cryopreserved AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Aurion Biotech

New P2 trial

Status and prospects for the development of regenerative therapies for corneal and ocular diseases. (PubMed, Regen Ther) - "Based on these advances, four regenerative therapy products for corneal epithelial disease, each employing distinct cell sources and culture techniques, have been commercialized since the regulatory approval of Holoclar® in Italy as a regenerative therapy product for corneal epithelial disease in 2015...The product was approved in Japan as Vyznova® in 2023. The development of regenerative therapies for retinal and ocular surface diseases is actively being pursued, and these therapies use somatic stem cells and pluripotent stem cells (PSCs), especially induced pluripotent stem cells (iPSCs). Accordingly, the eye field is anticipated to play a pioneering role in regenerative therapy development going forward."

Journal • Review • Ophthalmology

Aurion Biotech Receives Breakthrough Therapy Designation and Regenerative Medicine Advanced Therapy Designation for Its Drug Candidate AURN001 (Businesswire) - "Aurion Biotech...announced that the U.S. Food and Drug Administration (FDA) has granted both Breakthrough Therapy Designation (BTD) and Regenerative Medicine Advanced Therapy (RMAT) Designation for AURN001, the Company’s allogeneic cell therapy candidate for the treatment of corneal edema secondary to corneal endothelial disease."

Breakthrough therapy • Ophthalmology

CLARA: A Phase 1/2 Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1) (clinicaltrials.gov) - P1/2 | N=100 | Active, not recruiting | Sponsor: Aurion Biotech | Recruiting ➔ Active, not recruiting

Enrollment closed

CLARA: A Phase 1/2 Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1) (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Aurion Biotech

Trial completion date • Trial primary completion date

CLARA: A Phase 1/2 Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1) (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Aurion Biotech | Not yet recruiting ➔ Recruiting

Enrollment open

CLARA: A Phase 1/2 Multi-center, Randomized, Double-Masked, Prospective, Parallel- Arm Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1) (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Aurion Biotech

New P1/2 trial