InnoVec Biotherapeutics Advances Gene Therapy Delivery with IND-Approved IVB103 and Novel EASI-AAV Platform

According to Mordor Intelligence data, the global gene therapy market size is projected to reach USD 7.18 billion in 2024 and is expected to grow to USD 24.67 billion by 2029, with a compound annual growth rate (CAGR) of 28% during the forecast period (2024-2029). Gene therapy has opened a new pathway for the treatment of many diseases. Gene therapy drugs can exist in the form of DNA, RNA, or ribonucleoprotein (RNP), with the key technology being how to deliver them into cells. Despite this, the gene therapy sector continues to attract significant investment.Safe, precise, and effective delivery tools remain one of the most challenging problems in this field.。

Currently, gene therapy mostly focuses on genetic diseases. With the increase in R&D investment and technological advancements, gene therapy is expanding into more common diseases with larger markets. Notably, among the many gene-therapy-focused companies established after 2017, only a few concentrate on developing gene therapy delivery tools, and Innovecbio is at the forefront.In July 2024, IVB103 injection, based on the self-developed delivery vector by Innovecbio, received IND approval from the FDA. This marks Innovecbio's transition into a clinical-stage biotechnology company and represents a significant milestone in the development of Innovecbio's gene delivery tools.。

Dr. Cheng Wang, the founder of Innovecbio, graduated from Tsinghua University with a bachelor's degree, then pursued further studies at Columbia University under the guidance of Stephen Goff, a member of the National Academy of Sciences and an HHMI researcher, specializing in virology and molecular biology, and obtained his Ph.D. After graduating in 2015, he joined Regeneron Pharmaceuticals.Becoming one of the founding scientists of Regeneron's viral vector department, devoting to the frontier exploration in the fields of gene therapy and cell therapy, responsible for the construction of early-stage technical platforms for cell and gene therapy and the pipeline product layout.During this period, he led the determination of Regeneron's direction in the development of gene delivery tools, promoted the drug structure determination of multiple products, with the fastest already entering Phase 3 clinical trials.。

After accumulating industry experience, Wang Cheng had the idea of returning to China to start a business. However, due to his unfamiliarity with the domestic environment, he first worked as an early-stage biopharmaceutical investment consultant at Cowin Venture Capital for a period. During this time, domestic gene therapy startups became major fundraisers and gradually narrowed the gap with overseas companies in terms of product development. But in the research and development of innovative gene delivery tools, foreign countries still maintain a leading position, while domestic enterprises are in the catch-up stage. He also pointed out a common issue in the gene therapy field: due to the low efficiency of current delivery tools, there is often a need to increase dosage, which can easily trigger severe immune reactions and even lead to patient death.

This understanding prompted Wang Cheng and his team to focus on improving the efficiency and safety of delivery tools. In 2021, with the experience accumulated in the Chinese market, Wang Cheng founded a company, which he and his partners named INNOVEC (Innovecbio), an abbreviation for "Innovative Vector for Gene Therapy," directly reflecting their original intention to revolutionize gene delivery tools and advance gene therapy technology.

InnoVec Bio currently resides in the Seastar Pharmaceutical Health Innovation Park, which focuses on cutting-edge industry fields such as cell therapy, gene therapy, synthetic biology, and AI healthcare.Haixing Pharmaceutical Health Innovation Park, operated by Haining New Domain Urban Renewal Group with state-owned assets background in Haidian District, not only provides high-standard spatial carriers and industrial services for the biopharmaceutical industry but also establishes a full-chain industrial ecosystem covering "incubation + office," "R&D experimentation" to "pilot production." Through its unique "one center, five platforms" comprehensive service system, supplemented by complete property management and supporting support,The Haixing Medical Health Innovation Park has built a fertile ground covering the entire life cycle for Innovecbio and many other high-tech enterprises. In addition, this operational modelAccelerated the transformation efficiency of scientific and technological achievements and gradually built up a distinctive pharmaceuticals and health industry ecosystem.`, providing indispensable nourishment and support for the growth of enterprises within the park.`

Currently, gene delivery tools are mainly divided into two categories: viral vectors, such as adeno-associated virus (AAV) and lentivirus (LV); non-viral vectors, such as lipid nanoparticles (LNP). RNA can function in the cytoplasm, and LNP can directly deliver RNA to the cytoplasm, making it an efficient delivery vehicle; DNA must enter the nucleus to function, and so far, viral vectors remain the most effective tool for delivering DNA into the nucleus.Innovecbio chose to build a platform around AAV because AAV has extremely low pathogenicity and can remain in non-dividing cells for a long time, making it suitable for infecting most human tissues and organs such as the retina, brain, muscles, and heart.。

In the selection of indications, Wang Cheng's team decided to start with the ophthalmology field first. As a representative field for localized injection treatments, ophthalmology appears straightforward at first glance, but there are still many challenges in effectively delivering gene delivery tools to specific cells within the eye. For the treatment of common eye diseases, it is necessary to develop simpler drug administration methods, such as intravitreal injections, to broaden treatment accessibility. However, traditional gene delivery tools have limited infection efficiency on the retina when administered via intravitreal injection. Therefore, they...Dedicated to the modification and upgrading of existing vectors to enhance their infection efficiency in the retina, thereby meeting clinical needs.。

Currently, Innovecbio has built the EASI-AAV platform to address many pain points in the AAV vector and ophthalmic gene therapy fields, aiming to make all AAV technology and product development easier.

AAV is a member of the Parvoviridae family, a type of small virus with a diameter of approximately 20-26nm, containing a linear single-stranded DNA of about 4.7kb, incapable of autonomous replication, and non-enveloped. The recombinant adeno-associated virus vector (rAAV) used in research is a gene vector modified from the non-pathogenic wild-type AAV. Due to its diverse types, low immunogenicity, extremely low pathogenicity, broad range of host cells, and long-term gene expression in vivo, it is considered one of the most promising vectors for gene research and gene therapy.

However, the current adeno-associated viruses (AAVs) are all developed in mice or NHPs, with issues such as low conversion rates from animals to humans, tissue targeting, infection efficiency, and immune responses being the most prominent. In addition, problems like the limited packaging capacity of AAVs themselves and high production costs make technological innovation urgently needed for AAVs as gene therapy tools. To address this,One of Innovecbio's strategies is to modify viral vectors so that they can recognize and utilize specific receptors on the surface of target cells, thereby achieving precise tissue targeting.。

In addition,Under the EASI-AAV technology platform, the company has also developed technologies such as EASI-FIND, EASI-Expand, and EASI-Stable.EASI-FIND is a concept developed by Innovecbio based on the "from human to human" philosophy——Starting from humans, driven by AI, developing AAV delivery vectors suitable for the human bodyTraditionally, AAV development starts with animals, and the resulting vectors often exhibit low infection efficiency in humans or fail to infect the corresponding tissues, as there is significant species variation in viral infections.EASI-FIND aims to develop novel tissue-targeted AAVs in a simple way, overcoming the barriers of translation from animals to humans.。EASI-Expand and EASI-Stable focus on solving issues such as AAV packaging capacity and the complexity of the production process.。

Taking AAV for intravitreal administration as an example, traditional vectors, whether administered via intravitreal injection or subretinal injection, have difficulty reaching bipolar cells and photoreceptor cells, whileInnovecbio's vector developed based on the EASI-AAV platform for intravitreal injection can effectively infect bipolar cells and photoreceptor cells.Wang Cheng specifically mentioned: "When choosing this indication, we will pay special attention to which genetic defects in the two types of cells can lead to the disease."

In addition,Innovecbio's fully human nucleic acid delivery system (hVLP) is also under research for targeted modifications of the vector.hVLP is a nucleic acid delivery system entirely composed of human proteins, which can make the delivery system have the efficiency of viral vector systems and the advantages of non-viral systems such as ease of modification and repeatable delivery. It is reported that currently, Innovecbio...Complete the preliminary validation of the system and submit the patent application.。

It is worth mentioning that,Since the company was founded in 2021 and experiments were initiated, the Innovecbio team has achieved results within a short span of three years.. July 26, 2024,Innovecbio's IVB103 Injection Receives FDA IND Approval Ahead of Schedule, Officially Entering Clinical Trials

IVB103 Injection is a drug developed on the basis of Innovecbio's independently researched and developed novel vector for intravitreal administration to treat neovascular age-related macular degeneration (nAMD). Wang Cheng mentioned: "Preclinical data show that IVB103 is superior to advanced products of the same type currently under research internationally, demonstrating "best in class" potential.。In the Information Request, the FDA had only one question regarding the CMC of IVB103 and no issues with the Non-clinical section. This demonstrates the good safety and drugability of the vector independently developed by Innovecbio, which also became a prerequisite for the company to receive the FDA's IND approval in advance.”

Innovecbio's another重磅pipeline IVB102 is a drug developed based on the company's self-developed novel vector for the treatment of X-linked retinoschisis (XLRS).At the beginning of 2024, IVB102 Injection successively received the Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA).In preclinical studies, IVB102 injection has shown astonishing efficacy in model animals. Four to eight weeks after treatment with IVB102 injection, the cystic cavities caused by retinoschisis have largely disappeared. After 16-24 weeks of administration, the visual electrophysiological signals of mice recovered to a level comparable to that of wild-type mice, significantly outperforming similar products globally. XLRS is a type of X-linked recessive retinal disease, with an incidence rate of approximately 1/15,000 to 1/30,000, predominantly affecting males and exhibiting familial inheritance characteristics. The disease can manifest as early as two to three years old, causing varying degrees of vision impairment, characterized by inner retinal schisis, macular schisis leading to spoke-like changes, and peripheral retinal schisis. Electroretinogram (ERG) shows a negative waveform with a significant decrease in b-wave amplitude, which may be complicated by vitreous hemorrhage and retinal detachment. "Waiting for blindness" seems to have become the foreseeable fate for patients. RS1 is the only XLRS-causing gene discovered so far, but there are currently no effective treatments for XLRS available domestically or internationally.Currently, the IVB102 injection is undergoing an investigator-initiated clinical trial at Peking Union Medical College Hospital, with Professor RuiFang Sui as the principal investigator. The trial has completed patient enrollment for all low, medium, and high dose groups. Subjects have shown good conditions post-administration, with no serious adverse events reported. Preliminary efficacy observations indicate significant improvements in central retinal thickness, visual acuity, and static visual field.

When discussing the advancement of the pipeline, Wang Cheng emphasized that this process is not only a technical validation process but also a key step in enhancing the value of the technology. The companyAdvancing collaboration with research teams from universities and hospitalsHe looks forward to attracting more companies and research institutions to use Innovecbio's delivery technology for collaboration after achieving clinical success, meeting more scientific research and clinical needs.