Innostellar Biotherapeutics Announces Positive Phase I Clinical Trial Results for LX102, an AAV-Based Gene Therapy for Neovascular AMD

Recently, at the invitation of Professor Philip Rosenfeld, an internationally authoritative ophthalmology expert, Innostellar Biotherapeutics presented the clinical trial results of its self-developed LX102 gene therapy for nAMD at the Angiogenesis, Exudation, and Degeneration 2024 conference.

Professor Sun Xiaodong from the National Clinical Research Center for Ocular Diseases and the First People's Hospital of Shanghai reported in detail on behalf of the principal investigators of the project regarding Innostellar Biotherapeutics’ LX102 IIT (investigator-initiated clinical research conducted by the First People's Hospital of Shanghai) 1-2 year results and China Phase I clinical trial outcomes. LX102 has accumulated over 20 clinical cases, demonstrating good safety and efficacy.

The first subject receiving LX102 has been followed up for up to 18 months post-dosing, maintaining stable and improved vision without any supplementary treatment.In the Phase I study, all (9/9) medium- and high-dose subjects receiving LX102 did not require supplemental treatment with anti-VEGF agents.；The improvement of visual acuity is similar to existing antibody or fusion protein drugs.All studies on ocular lesion activityAchieve stable control。The average age of patients in this group was 71 years. Before receiving LX102 treatment, the average annualized number of anti-VEGF treatments was 8 to 9 times, comparable to subjects enrolled in similar foreign investigational products. After receiving LX102 treatment, the proportion of subjects requiring supplemental treatment was significantly lower than that of similar foreign investigational products, with all observed lesions showing improvement. Among the patients who completed the 6-month follow-up after dosing, only one case (1/11) required antibody supplementation, and the effective dose was lower.Showed a superior trend.

The other two gene therapy drugs at this conference also reported their respective clinical trial results. The latest Phase II clinical study results of 4D-150 showed that, six months after administration, 50% (10/20) of the low-dose group and 37% (7/19) of the high-dose group received supplemental anti-VEGF treatment. Preliminary results from the latest Phase II clinical study of ABBV-RGX-314 administered via subretinal injection for nAMD indicated that, six months after administration, approximately 33% of subjects (4/15 in the medium-dose group and 6/15 in the high-dose group) required supplemental anti-VEGF treatment. (Source: conference data)

The meeting also reported the results of Innostellar Biotherapeutics' previous IIT study on intravitreal injections for nAMD over 18-24 months, showing similar efficacy data, with clinical improvements lasting over two years and no patients requiring supplemental treatment (0/6).

The participating experts had a heated discussion on the above results. Compared with other existing approved or researched long-acting treatment methods, gene therapy achieves more stable lesion control (for 2 years or even longer) through a single administration and is accumulating an increasing amount of efficacy and safety data. It is the most promising candidate drug to solve the problem of the current need for repeated invasive dosing in AMD treatment. Regarding the route of administration, the presenters at the meeting pointed out that subretinal injection is the only gene therapy administration method proven by RCT and verified by commercialized drugs. Before LX102 subretinal administration, there is no need for prophylactic application of corticosteroids, and no drug-related immune inflammatory reactions were found during the trial, showing good potential in treating common diseases like AMD.Safety Advantages。The current superiority results also prove that LX102, through optimized and improved molecular design combined with subretinal local administration, can achieve better effects on the outer retina.Lesion-specific expression, and is also expected to play an advantage in the treatment of refractory PCV subtypes in the future.

The results released at this conference mark the first international disclosure of formal clinical trials for China-developed nAMD gene therapy product, providing strong clinical evidence for the safety and efficacy of LX102 as a leading nAMD gene therapy product.

Age-related Macular Degeneration (AMD) is one of the most common blinding eye diseases in the elderly. Neovascular AMD, also known as wet age-related macular degeneration (nAMD), can cause severe acute vision loss. Although it accounts for only 10%-20% of AMD cases, it is responsible for 90% of AMD-related blindness. The current standard treatment usually involves intravitreal injections of anti-VEGF drugs at intervals of one or two months, with patients requiring an average of 6-12 injections per year, some needing lifelong treatment. Interruption of treatment and under-treatment lead to a decline in long-term treatment outcomes and irreversible vision damage. As a technological breakthrough, gene therapy will significantly reduce the injection frequency required for nAMD patients and is expected to become a first-line maintenance therapy for nAMD in the future.

Since 2021, Innostellar Biotherapeutics has collaborated with the National Clinical Research Center for Ocular Diseases to conduct an Investigator-Initiated Trial (IIT) on the gene therapy LX102 for nAMD, making it the first gene therapy drug in China for this indication to be used in humans. Although the number of cases in this one-year follow-up data is small, all patients have shown good and stable anti-VEGF efficacy lasting up to one year after a single dose. Compared with similar drugs abroad, this product demonstrates good safety and efficacy at lower doses. On December 20, 2023, the Phase II clinical study of LX102 held a kick-off meeting at the National Clinical Research Center for Ocular Diseases, officially initiating patient enrollment for Phase II clinical trials. Innostellar Biotherapeutics looks forward to enabling patients to benefit more from anti-VEGF treatment through gene therapy, achieving long-term stability and maintaining a normal quality of life with a single injection.

The Angiogenesis Conference is an authoritative meeting in the field of international ophthalmology and retinal disease new drug development. Hosted by the Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, the top-ranked ophthalmology hospital in the U.S. for 15 consecutive years, since its inception in 2004, it has been dedicated to presenting cutting-edge clinical research findings through multiple rounds of expert selection. The conference focuses on advancements in diagnosis and novel therapies for ocular neovascularization, exudative, and degenerative diseases. Attendees include prominent scientists and clinical experts from various fields of ophthalmic drug development, including the National Eye Institute, the top ten U.S. ophthalmology centers, and globally renowned pharmaceutical companies. With the groundbreaking results of several major ophthalmic products such as Regeneron's Aflibercept, Novartis' Brolucizumab, Roche's Faricimab, and Apellis' APL-2 being unveiled at the conference, its scope and influence have expanded globally, making it a core forum for the release and discussion of pre-market ophthalmic drug research findings.

Professor Philip Rosenfeld, as an authoritative expert in retinal diseases in the United States, is the principal investigator and research project leader of several groundbreaking clinical trials for age-related macular degeneration (AMD). He has played a decisive role in the clinical trials of anti-vascular endothelial growth factor (VEGF) therapies, as well as in the diagnosis and disease management of macular diseases using OCT. He is considered one of the leaders in new drug development and translational clinical research in the field of ophthalmology. Throughout his career, Dr. Philip Rosenfeld has received numerous prestigious awards, including the Senior Achievement Award from the American Academy of Ophthalmology (AAO), the Richard and Hinda Foundation Award from the Macula Society, and the J. Donald Gass Award from the Retina Society.

In recent years, ophthalmic gene therapy has developed rapidly worldwide. Innostellar Biotherapeutics was invited to participate in the Angiogenesis conference this time and exchanged ideas with numerous peers. The clinical results presented at the conference once again confirmed the superior efficacy trend of the company's products in similar studies, which is the result of Innostellar Biotherapeutics' deep understanding and accumulation in ophthalmic AAV molecular design, clinical-grade production processes, and extensive clinical development experience.

About LX102 Injection

LX102 Injection, an nAMD gene therapy independently developed and manufactured by Innostellar Biotherapeutics, has a clear mechanism of action and proven efficacy. The product uses an AAV vector to deliver DNA expressing an anti-VEGF fusion protein into retinal cells, ensuring long-term expression of the anti-VEGF protein within the patient's eye. In previously conducted investigator-initiated clinical studies, LX102 demonstrated good tolerability and showed long-term efficacy in improving vision among multiple patients. LX102 received clinical approval from China’s CDE on December 23, 2022, and from the U.S. FDA on December 22, 2023.

Statement:The content of this article is intended for knowledge sharing. All content is for reference only and does not constitute any advice.