Eluminex Biosciences (Suzhou) Limited (Eluminex), an ophthalmology-focused biotechnology company headquartered in Suzhou, China with a US-subsidiary office in the San Francisco Bay Area, California, announced today that it has acquired certain assets and the related global development and commercialization rights for a novel oral therapy, zuretinol acetate (zuretinol), from Retinagenix Holdings, LLC (Retinagenix), a privately-held ophthalmic company based in Seattle, Washington. Zuretinol is an investigational treatment that is currently being developed to treat rare forms of childhood blindness in patients with LCA or RP caused by mutations of the RPE65 or LRAT gene.

"The addition of zuretinol into our growing retinal disease pipeline further bolsters our commitment towards the development of innovative therapies for vision-threatening diseases around the world," said Charles Semba, MD, Chief Medical Officer of Eluminex. "Currently, the only approved treatment for LCA and RP due to RPE65 and LRAT mutations is gene therapy which requires the child to undergo surgery and can treat only a small portion of the retina. Zuretinol offers hope in the ability to treat the entire retina and both eyes simultaneously either as a monotherapy treatment or adjunctive to gene therapy in restoring vision to these children and young adults."

Under terms of the agreement, Eluminex will make an upfront payment and earnout payments to Retinagenix for the purchase of the assets. The earnout payments to Retinagenix shall include (a) clinical, regulatory, and commercial milestone payments and (b) payments based upon worldwide net sales of products and the sale or use of priority review vouchers. The closing of this transaction is subject to certain customary conditions.

"Our focus at Retinagenix has been to see the zuretinol clinical program advance and for the drug to obtain regulatory approval in order to provide a safe, oral therapy for children and adults with these debilitating retinal degenerations. We believe Eluminex Biosciences is uniquely situated to complete the zuretinol development program and efficiently gain global regulatory approval for the compound," said David Saperstein, MD, Chief Medical Officer of Retinagenix.

About the Zuretinol Retinal Rare Pediatric Disease Program

The Eluminex zuretinol program (EB-109) is a clinical stage, novel, oral therapy for the treatment of a rare form of childhood blindness in patients with LCA or RP caused by mutations of the RPE65 or LRAT gene. EB-109 is regulated as a small molecule pharmaceutical product and is anticipated to enter a global Phase 2b/3 pediatric study in 2H 2022 to confirm its efficacy and safety. Orally administered zuretinol has been previously evaluated in 144 human subjects in 8 clinical studies, including healthy subjects, patients with recessive RPE65/LCA[1],[2], autosomal dominant RPE65[1],[2], and adults with early age-related macular degeneration (AMD) with poor night vision[3], which has demonstrated that zuretinol appears safe and well-tolerated and can rapidly improve visual function.

The zuretinol program was granted Orphan Drug Designation by the United States Food and Drug Administration (FDA) and the European Medicine Agency (EMA). It has also received FDA Rare Pediatric Disease and Fast Track designation and is eligible for a Rare Pediatric Disease Priority Review Voucher (PRV) which is transferable and allows the holder Priority Review (6 months) instead of the standard 10 months for any future regulatory submission.

About LCA and RP Caused by RPE65/LRAT Mutations

Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration and Leber congenital amaurosis (LCA) is a severe inherited form of retinal degeneration, each have a prevalence of approximately 1 in 3,000-4,000 and 1 in 33,000 live births worldwide, respectively. About 5% of RP patients and 10% of LCA patients have mutations in the LRAT or RPE65 genes.

Mutations in RPE65 and LRAT cause both RP and LCA in humans where two key enzymes of the visual cycle, retinoid isomerase (RPE65) and lecithin:retinol acyltransferase (LRAT), are missing which cause severe impairment in rod photoreceptor function. These patients suffer from severe vision loss or eventual total blindness.

Currently, the only approved treatment for patients with RPE65 mutations is LUXTURNA? (voretigene neparvovec-rzyl) in the United States and the European Union. There are no approved treatments for LRAT mutations. LUXTURNA? is a gene therapy administered through subretinal injection into the diseased eye. Besides the high cost and the need to perform surgery and inject each eye separately, only about 15-25% of the injected retina is treated which leads to limited vision recovery. Long-term safety follow-up studies have reported adverse reactions including dyschromatopsia, glare, and probable surgery-related macular scar and thinning.[4] Therefore, an unmet needs exist for non-surgical, bilateral treatment of retinal dystrophies secondary to RPE65/LRAT mutations at improved cost.

About Zuretinol for Impaired Dark Adaptation (Night Blindness) in Early Dry AMD

Dark adaptation (night vision) is the ability for the eye to adjust from seeing in the light to seeing in dark or dim light environments. Research shows this function is compromised from the earliest stages of AMD and impairment increases as the disease progresses. Impaired dark adaptation (also referred to as night blindness or nyctalopia) has been observed in AMD at least three years before drusen are visible and there is a positive correlation between the degree of dark adaptation impairment and severity of AMD.[5],[6]

Future developments for zuretinol include potential treatment for impaired dark adaption in adult patients due to early AMD. A prior multicenter, placebo-controlled Phase 2a study of oral zuretinol in adult patients (N=43) with impaired dark adaptation in early-stage AMD demonstrated evidence of rapidly improved dark adaptation, glare recovery, and low luminance, low contrast best corrected visual acuity in patients receiving zuretinol compared to placebo and appeared safe and well-tolerated and provides support for further clinical development.[3]

About Eluminex Biosciences

Eluminex Biosciences is a privately-held clinical-stage biotechnology company focused on both global and regional development and commercialization of innovative therapeutics to fulfill unmet medical needs in the treatment and management of ophthalmic diseases. Eluminex is devoted towards innovating the next generation of first-in-class or best-in-class ocular therapeutics for vision-threatening or lifestyle-limiting ocular diseases.

In addition to the zuretinol program (EB-109), Eluminex has exclusively licensed global rights for the development and commercialization of an investigational clinical-stage biosynthetic cornea derived from recombinant human collagen Type III for the treatment of corneal blindness.

Eluminex is developing a pipeline of next generation protein therapeutics for retinal diseases (EB-101, EB-102, EB-105, and EB-107) including age-related macular degeneration, macular edema, and diabetic retinopathy; these assets are wholly owned and developed by Eluminex.

The Eluminex global headquarters and research and development center are located in Suzhou BioBay Industrial Park, China, with a US-subsidiary located in the San Francisco Bay Area. Eluminex is supported by three premiere global life science venture funds: Lilly Asia Ventures, Hillhouse Capital, and Quan Capital.

About Retinagenix Holdings, LLC

Retinagenix is a privately-held biotechnology company devoted to addressing the large and expanding unmet medical needs in genetically determined orphan diseases of the eye. Retinagenix was founded by Marco Northland, serial entrepreneur, and David Saperstein, MD, co-inventor of the technology behind the zuretinol program developed while Dr. Saperstein was at the University of Washington. Dr. Saperstein has been engaged in retina research for more than 30 years and is a practicing retinal surgeon.  

References:  

[1] Koenekoop RK, Sui R, Sallum J, Ingeborgh van den Born L, Ajlan R, et al. Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label Phase 1b trial. Lancet 2014; 384: 1513-20.   

[2]  Scholl HPN, Moore AT, Koenekoop RK, Wen Y, Fishman GA, et al. Safety and proof-of-concept study of oral QLT091001 in retinitis pigmentosa due to   

[3]  Eluminex Biosciences, Ltd (Suzhou), data on file.   

[4]  "Study investigates safety, efficacy of LUXTURNA in real-world clinical practice," Ocular Surgery News, September 23, 2021. https://www.healio.com/news/ophthalmology/20210923/study-investigates-safety-efficacy-of-luxturna-in-realworld-clinical-practice.  

[5] Owsley C, McGwin G, Clark ME, Jackson GR, Callahan MA, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration. Ophthalmology. 2016; 123: 344-351. 

[6] Echols BS, Clark ME, Swain TA, Chen L, Kar D, et al. Hyperreflective foci and specks are associated with delayed rod-mediated dark adaptation in non-neovascular age-related macular degeneration. Ophthalmol Retina. 2020; 4: 1059-1068.

Source: Eluminex Biosciences