EyeDNA Therapeutics Announces Positive 24-Month Data Presented at ARVO from Ongoing Phase I/II Trial of HORA-PDE6b Gene Therapy in Patients With Retinitis Pigmentosa Caused by Bi-allelic PDE6b Mutations

Clinically significant benefit in visual functions and good security profile of HORA-PDE6b is confirmed at 24 months follow-up

Phase I/II results will be discussed with US and European health authorities to define the optimal pathway to make HORA-PDE6b accessible to patients with PDE6b retinitis pigmentosa.

Paris, France, May 7, 2024 – eyeDNA Therapeutics (“eyeDNA”), a newly formed subsidiary of Coave Therapeutics (“Coave”), a genetic medicine company focused on developing life-changing therapies, today announces positive 24-month follow-up results of its phase I/II study. study (NCT03328130) evaluating the safety and efficacy of HORA-PDE6b, its investigational gene therapy for retinitis pigmentosa (RP) caused by bi-allelic mutations in the PDE6b gene (PDE6b RP). These data were reported in an oral presentation* on May 6, at the 2024 Association for Research in Vision and Ophthalmology (ARVO) meeting in Seattle, WA, USA.

The positive 24-month follow-up data presented confirms the results of the previous interim analysis of the trial conducted at the 12-month follow-up point and supports preparation for a registrational trial for HORA-PDE6b in patients with PDE6b RP. Further discussions with health authorities in the United States and Europe are planned to define the optimal pathway to make HORA-PDE6b available to patients with PDE6b RP.

To date, HORA-PDE6b has been administered in 17 evaluable patients aged 18 years and older with advanced PDE6b RP using two escalating doses in four consecutive cohorts. Treatment was administered in the more affected eye while the fellow eye served as an untreated control.

In a subgroup of clinical interest of six patients receiving the high dose, with less advanced disease (best corrected visual acuity (BCVA) score ≤ 75 ETDRS letters (≤ 20/32 Snellen equivalent), Goldmann visual field ( GVF) ≥ 10 degrees), positive efficacy results were reported at 24 months on BCVA and GVF results. The mean change in BCVA from baseline increased by +0.09 LogMar in the untreated eye, while acuity in the treated eye stabilized (+0.02 LogMar). Compared to baseline, the mean reduction in GVF was more than 300 deg² greater in the untreated eyes compared to the treated eye.

Interestingly, long-term data available from patients in the low-dose group (n=7) followed over a five-year period revealed that the BCVA of untreated eyes consistently decreased (increase from 0.05 to 0.08 LogMAR/year from the second year). ), which corresponds to the natural history of the disease. During this time, the mean change from baseline in BCVA of treated eyes in the same group is stabilized (between +0.03 and +0.06 LogMAR over the same follow-up period). The difference in mean change from baseline in BCVA between treated and untreated eyes at five years is 0.25 LogMAR (12 letters).

The story continues

Furthermore, the blue light full-field stimulation test (FFST) evaluating the function of the rods continues to show an improvement in the light perception threshold in favor of the treated eyes, considered clinically significant (improvement of almost six decibels). The interesting positive trend in retinal anatomical evaluation by Optical Coherence Tomography (OCT; horizontal length of the ellipsoid zone) observed at 12-month follow-up in the subgroup of clinical interest is maintained after 24 months.

After the 24-month study period, both doses were well tolerated (n=17). Five serious ocular adverse events (SAEs) occurred, two of which resolved, possibly related to HORA-PDE6b (one chorioretinitis and reduced visual acuity). Patients did not receive preventive oral corticosteroids.

An additional cohort of four to six younger patients aged 13 to 17 years with baseline GVF ≥20 degrees in each meridian and early stage disease is underway with three patients enrolled.

“The very encouraging safety and efficacy data observed in patients two years after treatment with HORA-PDE6b continue to support our view that this new gene therapy could provide significant clinical benefit to patients with PDE6b RP. This data will support our discussions with regulators to determine the optimal route to administer HORA-PDE6b to patients. declared Rodolphe Clerval, Managing Director. “At the same time, we continue to evaluate HORA-PDE6 in an expansion cohort of younger patients with less advanced disease, for whom treatment with HORA-PDE6b could have an even greater therapeutic impact. »

“PDE6b retinitis pigmentosa is a progressive and irreversible hereditary degenerative disease that causes significant visual impairment and blindness. These promising two-year safety and efficacy results are of great medical interest and could represent a significant step toward providing effective treatment to patients with this devastating disease. » » commented Dr. Jean-Baptiste Ducloyer, MD, Department of Ophthalmology at the University of Nantes.

*Summary 2134:

JB Ducloyer, et al. 12-Month Safety and Efficacy Evaluation of HORA-PDE6b, a Gene Therapy Targeting Patients With Retinitis Pigmentosa Due to a Biallelic Mutation in the PDE6B Gene

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About eyeDNA Therapeutics and HORA-PDE6b

eyeDNA Therapeutics, a wholly owned subsidiary of Coave Therapeutics, is a clinical-stage gene therapy company focused on developing life-changing therapies for inherited retinal disorders. Our lead program HORA-PDE6b, an AAV5-based gene replacement therapy, is being evaluated in a Phase I/II trial for the treatment of retinitis pigmentosa (RP) caused by bi-allelic mutations in PDE6b gene (PDE6b RP) (NCT03328130).

eyeDNA and Théa Open Innovation (“TOI”) are partners for the development and commercialization of HORA-PDE6b. eyeDNA is responsible for the global development of HORA-PDE6b and retains commercial rights to the product in the United States, Japan, South Korea, China and other territories outside Europe. In Europe and certain other countries, HORA-PDE6b is co-developed by Coave and TOI under a licensing and development agreement with exclusive rights granted to TOI to market HORA-PDE6b in these territories.

About Coave Therapeutic

At Coave Therapeutics, we are leading the transition of genetic medicine from rare to prevalent diseases, starting with neurodegenerative and ocular diseases. Our proprietary ALIGATER™ (Advanced Vectors-Ligand Conjugates) platform introduces chemical modifications to AAV capsids or lipid nanoparticles (LNPs) to overcome the limitations of current vectors in terms of efficacy, safety and manufacturability.

With low doses and optimized routes of administration, our conjugated vectors demonstrated significantly improved transduction and biodistribution in the central nervous system and eye in different species. Our diverse portfolio of novel genetic medicines has the potential to transform the lives of people with rare and prevalent neurodegenerative and ocular diseases, including in genetically and non-genetically defined indications.

Coave recently established its subsidiary eyeDNA Therapeutics to focus on the development – ​​up to marketing authorization application – of its unique gene therapy HORA-PDE6b for the treatment of inherited retinal diseases caused by mutations in the human PDE6b gene.

Headquartered in Paris, France, Coave Therapeutics is backed by leading international life sciences investors. For more information about the science, pipeline and people, please visit https://coavetx.com/ and follow us LinkedIn.

CONTACTS
eyeDNA Therapeutics and Coave Therapeutics
Rodolphe Clerval, CEO
[email protected]

MEDiSTRAVA
Sylvie Berrebi, Leïla Adlam, Mark Swallow
[email protected]