CRX

PARIS, April 3, 2025 /PRNewswire/ -- Variant, a company dedicated to developing innovative treatments for orphan inherited eye diseases, and the Rare Ocular Diseases Center at the University of Campania Luigi Vanvitelli (UCLV) in Naples today announced that they have received positive feedback from the European Medicines Agency (EMA) on VAR002, an adeno-associated viral vector gene therapy targeting inherited retinal dystrophies linked to CRX mutations. This consultation and subsequent feedback from the EMA ensure that the non-clinical development plan of VAR002 is suitable for a future first-in-human clinical trial. It also confirmed that the planned pivotal toxicology study design will support a Marketing Authorisation Application in the EU. EMA Scientific Advice : Positive Feedback on VAR002 The European Medicines Agency (EMA) provided scientific advice supporting the non-clinical development plan of VAR002, an adeno-associated viral vector gene therapy targeting inherited retinal dystrophies linked to CRX mutations. The preclinical program, including pivotal toxicology and biodistribution studies, was deemed appropriate to advance towards a first-in-human clinical trial. This endorsement confirms that the data generated so far adequately supports the safety and pharmacological profile of VAR002, ensuring a solid foundation for clinical translation. The planned study will assess VAR002 in patients with CRX-associated retinal diseases, addressing a critical unmet medical need in ophthalmic gene therapy. The EMA also confirmed that the planned pivotal toxicology study design for VAR002 aligns with the requirements to support a future Marketing Authorisation Application (MAA) in the EU. The study, conducted in compliance with Good Laboratory Practice (GLP), will assess the safety, biodistribution, and potential toxicity of VAR002, ensuring a comprehensive evaluation of its risk-benefit profile. The EMA acknowledged the study's relevance in addressing key regulatory expectations for gene therapies, reinforcing the robustness of VAR002's non-clinical development strategy as it advances towards clinical trials and eventual market approval. Securing the Development Pathway for VAR002 "The EMA has highlighted the need for particular attention to the potential risks associated with CRX transgene expression outside of photoreceptor cells due to autoactivation of the hGRK1 promoter" says Denis Cayet, CEO of Variant. "These recommendations are instrumental in strengthening the robustness of our preclinical studies and, ultimately, securing the development pathway for VAR002, ensuring the highest safety and efficacy standards as we progress toward clinical trials." ABOUT VAR002 VAR002 is a recombinant adeno-associated viral (rAAV) vector initially developed to treat Leber's congenital amaurosis, Retinitis pigmentosa, and Cone-rod dystrophy due to a mutation in the CRX gene. This gene replacement therapy provides an unmutated copy of the human CRX gene to replace the defective gene, inducing the expression of a functional CRX protein in the photoreceptors. VAR002 is administered as a sterile suspension of viral particles, injected directly into the subretinal space. This triggers the expression of the transgene in the rods and the cones. Recent discoveries have further demonstrated the potential of VAR002 beyond CRX-related inherited retinal dystrophies, particularly in diseases associated with defects in phototransduction pathways and ciliopathies. Preclinical studies in relevant animal models, including CEP290-associated ciliopathies, have highlighted its capacity to restore retinal function in a broader range of genetic disorders, paving the way for expanded clinical applications. ABOUT VARIANT Variant is a biotechnology company dedicated to developing innovative gene therapy solutions for inherited retinal diseases. Variant focuses on leveraging retinal transcription factors to restore photoreceptor function in severe retinal dystrophies. Variant has initiated a Translational Preclinical Task Team, working alongside Professor Francesca Simonelli (Naples Hospital, Italy), to accelerate the transition from research to clinical application. ABOUT The Centre for Rare Ocular Diseases Center at University of Campania Luigi Vanvitelli, Naples, Italy. The Centre for Rare Ocular Diseases of the academic hospital University of Campania Luigi Vanvitelli offers diagnostic, rehabilitative and therapeutic courses for patients suffering from hereditary eye diseases. Recently, a "Telethon Advanced Ocular Therapy Unit" was created at the Centre, unique in Italy and among the few in Europe, dedicated to clinical studies aimed to evaluate innovative therapeutic strategies for the treatment of rare ocular diseases. This way, patients can be enrolled in major clinical studies for hereditary eye diseases. CONTACT: Dorothée M. +33 9 53 73 68 15 [email protected] SOURCE Variant WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

PARIS--(BUSINESS WIRE)-- Variant, a company dedicated to developing innovative treatments for inherited eye orphan diseases, announces the decision of the European Commission to grant Orphan Drug Designation (ODD) for VAR002 for the treatment of Leber congenital amaurosis (LCA) and Cone-rod dystrophy (CORD). The decision is based on a positive opinion from the European Medicine Agency’s (EMA) Committee for Orphan Medicinal Products (COMP). VAR002 is a CRX-expressing AAV vector designed as a relevant therapeutic approach for gene supplementation and a promising drug candidate for mutation-agnostic gene therapy. VAR002 prevents photoreceptor degeneration without adverse effects linked with CRX overexpression. The ODD is an essential landmark in the development of VAR002 that, along with the strong intellectual property moving on to the regional phase (EU, US and Japan), consolidates the position of VAR002 as CRX worldwide leader compared to the few other potential treatments involving transcription factors. “With VAR002, I have the opportunity to approach the unmet needs of patients carrying dominant CRX mutations. We are excited to move this program to the clinic in collaboration with a new team experienced with translational development”, comments Jerome ROGER, project manager. “Our strategy will target LCA, CORD or RP associated with CRX mutations and many not CRX related IRDs where the neuroprotective capacity had been proved. The positive results of the preclinical studies of VAR002 showed efficacy and a good safety pro the defined dose”. Denis CAYET, Variant CEO, comments, “With the VAR002 ODDs and patent, VARIANT develops solid protection of its know-how on retinal transcription factors. As a result, we can move forward to bring an excellent new solution to CRX patients! And this future perspective makes me happy !”. ABOUT VAR002 VAR002 is a recombinant adeno-associated viral (rAAV) vector developed to treat LCA, CORD and RP due to a mutation in the CRX gene. This gene replacement therapy provides an unmutated copy of the human CRX gene to replace the defective gene, inducing the expression of a functional CRX protein in the photoreceptors. VAR002 is administered as a sterile suspension of viral particles, injected directly into the subretinal space. This triggers the expression of the transgene in the rods and the cones. ABOUT VARIANT Variant is a biotechnology company that develops innovative products in the ophthalmology sector. Variant aims to provide the pharmaceutical industry with solid proof-of-concept data to establish therapeutic strategies for rare visual diseases. The company has several scientific collaborations specialized in antisense oligonucleotides (ASO)°, genome analysis, production and administration of AAV vectors, and human retinal organoids. Our associated partners are well-positioned to test therapies for dominant and recessive retinal dystrophy forms, notably orphan diseases, such as congenital Leber Amaurosis, cone-rod dystrophies, and retinitis pigmentosa. Variant’s leading preclinical portfolio has a diversified risk profile: the company specializes in using “transcription factor”, which intervene very early in the development of photoreceptors to relaunch the differentiation of cones and rods in the retina. The company achieved an exciting combination of therapeutic approaches. On one side, for moderate CRX CORD a less invasive intravitreal administration of encouraging ASO treatment. And, on the other side, the experimented subretinal administration of AAV vector for severe CRX LCA & RP. Plus d’informations sur Cliquez et entrez en contact avec nous sur Linkedln.