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2022-03-28
INNORNA: Explore Frontier of mRNA Application Based on Platform Technology

Our company officially announced the completion of 120 million US dollars in Series B funding in March 2022, totaling the size of our equity financing to more than one billion RMB since the establishment of the company. Currently, the company has applied for multiple technology patents with important application values centered on mRNA and the LNP technology platform and has completed the layout of multiple R&D pipelines.

High-quality companies on the cutting-edge track are still favored by investors, despite a recent slowdown in the biomedical equity financing market under the disturbance of multiple factors after the Chinese New Year.

The previous round of financing has reserved sufficient funds for the follow-up clinical trials of our existing R&D pipeline. With the fund from this round, our company will continue to expand the boundaries of R&D for mRNA drugs based on our technology platform and to develop more new R&D pipelines that have not yet been touched.


Looking for Best-in-Class LNP structure

According to the central dogma, messenger RNA (mRNA) is a type of single-stranded ribonucleic acid that is transcribed from a strand of DNA as a template. It carries genetic information and can guide protein synthesis. The working mechanism of nucleic acid drugs is to send the modified mRNA molecules into the cytoplasm which uses its own nucleotides for transcription and expression to generate the required proteins. In theory, mRNA can express any protein and therefore can treat almost all protein-based diseases, including various types of cancer, infectious diseases and some rare diseases. In addition, as mRNA is an important bridge connecting DNA and proteins, the development of drugs with mRNA targets is expected to solve the medicine manufacturable limitations of existing targets and solve the challenge of “untargetable” and “unmanufacturable” traditional drugs.

However, while the potential of nucleic acid drugs is being tapped, the disadvantages of mRNA have begun to emerge as it is not able to enter cells to function and can be easily degraded by nucleases. Hence, the delivery technology that can protect and encapsulate mRNA into cells becomes the key to the development of nucleic acid drugs. Our company’s successful funding of USD 120 million in Series B proves that on the cutting-edge track of mRNA, companies that master the key delivery technology are bound to win the favor of capital despite the slowdown in the biomedical equity financing market.

The founder and CEO of our company, Dr. Li Linxian, believes that the development of nucleic acid drugs faces many challenges, including the instability of nucleic acid molecules in vivo, potential side effects of delivery systems, and the difficulty of developing nucleic acid drug delivery systems. In particular, mRNA has a larger molecular weight and carries many negative charges, which makes it difficult to enter the cell itself to function. Therefore, it needs to be wrapped by positively charged lipids during development. In addition, related lipids need to be ionizable, that is, to complete the encapsulation and dissociation of mRNA under different acid-base conditions, to achieve stable and effective targeted delivery and release.

To solve these problems, our company chose to independently build an LNP technology platform and designed and constructed various ionizable phospholipids. To accommodate different application scenarios, we analyze and optimize the synthesized LNP structure and activity data, simulate the delivery and therapeutic effect of nucleic acid drugs with high-throughput screening, and screen out the best-in-class LNP structures for specific needs. Since its establishment, our company has built a resource library containing nearly 5,000 LNPs to screen out LNP vectors for different treatment scenarios.


The core R&D team in charge of mRNA drug development

Dr. Li Linxian, the founder and CEO of INNORNA, used to be a student of Professor Robert Langer at MIT who is the leading expert in the field of mRNA and the technology founder of Moderna. In 2017 Dr. Li was named China’s “Innovative 35 people Under 35” because he developed a new generation of LNP technology for mRNA delivery. In 2019, Dr. Li led the R&D team to synthesize a large number of LNPs in a short period of time by using parallel synthesis and screened out suitable LNPs as vectors for mRNA vaccines by using high-throughput screening technology. The results have been published in an article in Nature Biotechnology and Dr. Li is the only designer of the chemical structure of the liposome in the article.

It was this article, which was published in one of the world’s top journals, that made Zhang Junjie, the founding partner of HHF Investment, got to know Dr. Li. Dr. Zhang Junjie was deeply involved in Shenxin’s series B funding and was impressed by the depth of the article and the Chinese identity of the author. “We reached out to Dr. Li immediately and invited him to be our industry consultant. We were also impressed by the synthesized LNP and excellent data generated in the experiment,” he said.

Dr. Li Linxian’s contribution to the development of LNP technology does not stop there. The lipid structure he designed and discovered in the early stage is the core part of the two ionizable cationic lipids used in the FDA-approved mRNA vaccine for Covid-19. Then Acuitas and Moderna further drew on the biodegradable design of Alnylam and finally designed two types of lipids ALC0315 and SM102.

“INNORNA has built a diverse new library of LNPs. It has made amazing breakthroughs in patents, safety and effectiveness, as well as multi-organ targeted delivery, which have been verified in large and small animals,” said Dr. Liu Dan who highly recognized the LNP technology of INNORNA.


Power of the platform-based technology company

In addition to the LNP technology platform that solves the delivery problem of nucleic acid drugs, the mRNA synthesis technology platform our company developed independently has also provided great support to the new drug research and development. To address the problem of high-efficiency expression of mRNA, our company has increased the mRNA stability and protein expression time from the design end based on research, and improved protein expression through codon optimization in the coding region. At the same time, supported by both nucleotide modification and efficient capping technology, the non-coding region and the coding region form synergy to enhance mRNA stability and its expression efficiency.

Based on this, the overall technology and expression of our mRNA products have been at the world’s leading level, and have been verified in large animal experiments.

According to Dr. Li Linxian, whether mRNA vaccines and nucleic acid drugs are safe and effective, and have fewer side effects, is inseparable from the LNP and mRNA composition of related drugs. By mastering the two core technologies of LNP and mRNA synthesis, INNORNA can develop safer and more effective mRNA vaccines and nucleic acid drugs which have better market prospects but have higher requirements for delivery technology.

“Rather than focusing on one specific product, we value INNORNA as a platform company, as it can continuously develop various new mRNA or nucleic acid drugs,” said Dr. Zhang Junjie. In his view, very few teams in the world can truly master key technologies such as LNP delivery and mRNA synthesis. Led by Dr. Li Linxian, the R&D team of INNORNA have extensive experience in R&D and owns leading underlying technology, both of which ensure the growth of INNORNA.


INNORNA team development and external cooperation

At present, our company has built multiple R&D pipelines centered on mRNA and the LNP technology platform. Some pipelines are about to complete preclinical trials. To support the advancement of R&D pipelines, our company has built R&D and CMC teams with nearly 200 employees, including several senior executives with many years of experience in international pharmaceutical companies such as GSK, Pfizer and BMS. We also have a 4,500 square meter R&D laboratory and a 2,500 square meter pilot workshop.

Our company is open to cooperation opportunities to partner with companies in the industry that are deeply involved in this sector to meet unmet clinical needs.

Dr. Li Linxian said: “In the future, INNORNA hopes to truly become a platform company for the development of new mRNA drugs built on the self-developed LNP and mRNA synthesis technology platforms. Based on platforms, the company will not be limited to a certain type of nucleic acid drug. Instead, we will continue to explore the application boundaries of mRNA technology and bring Best-in-Class and First-in-Class innovative drugs to clinical treatments.“