From Suzhou to the world: UgeneX pacts with AviadoBio, licensing gene therapy asset in deal worth up to $413 million

On October 9, Suzhou UgeneX Therapeutics Co., Ltd. ("UgeneX") announced that it has entered into a strategic agreement with UK-based biotechnology company AviadoBio, granting AviadoBio an exclusive option for the overseas development and commercialization of its optogenetics pipeline asset UGX202. UGX202 is an adeno-associated virus (AAV) gene therapy in clinical development for the treatment of patients with retinitis pigmentosa (RP). A second, undisclosed indication is expected to enter the clinical stage by the end of this year.

According to the agreement terms, AviadoBio holds the option to obtain a global exclusive license for the development and commercialization of UGX202 for RP and other indications outside the Greater China region. If AviadoBio exercises this option, UgeneX will be eligible to receive up to $413 million (approximately RMB 2.9 billion) in upfront payment, development and sales milestone payments, as well as royalties on net sales.

In the field of gene therapy, the eye represents a particularly attractive target organ. The blood-retinal barrier creates an immune-privileged environment, maintaining relative isolation from the systemic immune system. This anatomical containment enables localized drug delivery. Furthermore, the ability to administer therapy directly to the eye requires lower therapeutic doses compared to systemic routes, resulting in reduced costs and significantly improved safety profiles.

Currently, the primary focus of ophthalmic gene therapy revolves around inherited retinal diseases (IRDs) caused by single-gene mutations. These conditions include retinitis pigmentosa (RP), choroideremia, Leber hereditary optic neuropathy (LHON), Leber congenital amaurosis (LCA), Stargardt disease, achromatopsia, and X-linked retinoschisis.

Among these, retinitis pigmentosa stands as a progressive inherited retinal disease involving more than 100 distinct gene mutations. The degeneration of photoreceptor cells in RP leads to gradual, irreversible vision loss, making it a leading cause of visual impairment and blindness worldwide. According to NIH statistics, the global prevalence of RP is approximately 1 in 5,000 people, with late-stage cases constituting 29% of all patients.

In 2021, Nature Medicine published a landmark case study documenting functional visual recovery in an RP patient following optogenetic therapy. This represented the first reported instance of functional recovery in a neurodegenerative disease patient using optogenetic approaches. While gene-editing therapies show efficacy limited to early-stage patients, no other treatments have received regulatory approval for retinitis pigmentosa.

UGX202 is an innovative, single intravitreal injection AAV (adeno-associated virus) vector-based gene therapy independently developed by UgeneX for treating retinitis pigmentosa. Currently in clinical development, this therapeutic candidate employs cutting-edge optogenetics technology to deliver genes encoding light-sensitive proteins to retinal ganglion cells, effectively "reprogramming" them into light-sensing cells. This process replaces lost rod and cone cells and reconstructs visual pathways.

UGX202's distinctive feature lies in its "universal" mechanism that transcends specific gene mutations. Its therapeutic effect remains independent of the patient's particular pathogenic gene mutation, making it applicable to broad patient populations. This approach demonstrates potential for treating not only retinitis pigmentosa but also various other inherited retinal diseases and macular degeneration.

In September this year, the first patient received UGX202 treatment at the Eye & ENT Hospital of Fudan University. This investigator-initiated trial (IIT) aims to evaluate the safety and efficacy of UGX202 in late-stage RP patients. Additionally, another indication for this therapy is scheduled to enter clinical research by year-end.

UgeneX's collaboration partner AviadoBio, founded in 2019, specializes in developing gene therapies for neurodegenerative diseases including frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Commenting on the collaboration, AviadoBio stated: "We are excited to expand our clinical-stage neurodegenerative disease pipeline from the brain to the eye, applying our core expertise in targeted vector delivery, highly effective target proteins, and rapid translation to address retinitis pigmentosa and other retinal diseases."

Beyond the ophthalmic gene therapy UGX202 acquired through this partnership, AviadoBio's core pipeline includes the neuroscience gene therapy candidate AVB-101. This one-time administered AAV gene therapy is currently being evaluated in a Phase 1/2 clinical trial for FTD patients with GRN gene mutations. Previously, AVB-101 has received Orphan Drug Designation from both the US FDA and the European Commission, along with FDA Fast Track designation.

AVB-101 is designed to deliver a functional PGRN gene copy to the brain via an AAV9 vector, restoring normal PGRN expression. The therapy utilizes minimally invasive stereotactic neurosurgery for direct intrathalamic administration. This method leverages the brain's neural networks to enhance vector biodistribution, achieving widespread and robust gene expression. The thalamus maintains extensive connections with other brain regions, including the frontal and temporal lobes that play crucial roles in FTD symptomatology.

Preclinical studies have demonstrated that AVB-101 enables comprehensive PGRN expression throughout the brain while avoiding expression in serum or liver tissues, thereby minimizing off-target effects. Previous announcements noted that AVB-101's Phase 1/2 trial, designated ASPIRE-FTD, represents the first intrathalamic gene therapy administered to humans for treating adult neurodegenerative diseases.

This therapeutic candidate has garnered attention from Astellas. In October 2024, AviadoBio entered an agreement with Astellas concerning AVB-101, granting the latter rights to acquire a global exclusive license for developing and commercializing AVB-101 for FTD and other potential indications. Under the agreement, Astellas made a $20 million equity investment for AVB-101 licensing rights and paid up to $30 million upfront. Should Astellas exercise its option, AviadoBio would become eligible for up to $2.18 billion in licensing fees and milestone payments, plus royalties.

Collectively, both the $2.2 billion AVB-101 partnership established in October 2024 and the recent $413 million UGX202 collaboration demonstrate AviadoBio's strategic vision and substantial ambitions in the gene therapy arena.

Through the UGX202 partnership with UgeneX, AviadoBio is extending its neurodegenerative disease delivery and expression platform into the retinal domain, establishing an integrated "brain-eye" gene therapy strategy. This approach not only circumvents immunological risks associated with systemic administration but also targets the rare ophthalmic disease market with clearly defined unmet medical needs.

For UgeneX, as articulated by Dr. Wu Kai, Executive President of UgeneX, this collaboration not only reflects both parties' strong confidence in UGX202's clinical potential and market prospects, but also marks a significant milestone in UgeneX's globalization journey. It substantially demonstrates the UgeneX team's international perspective and R&D capabilities, along with the global value of its pipeline.