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Text | Chang Zeyu

Editor | Hai Ruojing

Recently, 36Kr learned that ReviR Therapeutics completed a USD 30 million Series A financing round. This round of financing was led by Longpan Investment, with continued investment from old shareholders CDH Investments, 5Y Capital, and Yayi Capital, and followed by Jingtai Technology and CMT Research Foundation (CMTRF).

This round of investment will be used to further build ReviR's independently developed AI drug development platform VoyageR, and combine AI technology with the ReviR team's rich drug development experience to continue to advance the preclinical and clinical development of existing Huntington's disease (HD) pipelines and pipelines related to various neurological diseases including Charcot-Marie-Tooth Disease (CMT) and Amyotrophic Lateral Sclerosis (ALS).

Founded in 2021, Xili Technology is a biotechnology company that combines AI technology to develop targeted RNA small molecule drugs. It uses cutting-edge technology and the AI ​​drug development platform VoyageR to conduct more effective and safe targeted RNA therapy research in order to solve the long-standing unmet clinical needs of tumors and genetic diseases.

With the deepening of understanding of genomics, proteomics and other fields, a large number of new drug targets have been discovered, but existing technologies are difficult to support the development of targeted drugs for most of these targets, so these targets are also called "undruggable targets." According to statistics, more than 80% of the pathogenic proteins related to human diseases cannot be targeted by current conventional methods.

How to overcome "undruggable" targets has become one of the core issues in the field of biomedicine. In recent years, protein degradation, gene editing, targeted RNA regulation and other methods have provided new ideas for "solving the problem".

"Since these targets are not druggable at the protein level, we might as well bypass the protein and target the more 'upstream' RNA, regulate disease-related proteins through mechanisms such as blocking translation, and thus achieve treatment of the disease," Li Yang, co-founder and chairman of Xili Technology, told 36Kr. Targeted RNA regulation can greatly expand the potential drug target library.

At present, the main forms of RNA drug development in the industry generally include nucleic acid drugs, RNA editing therapy and targeted RNA small molecule drugs. Li Yang pointed out that in theory, compared with gene therapy that requires AAV as a vector, small molecule drugs can be taken orally, which can improve the convenience and compliance of patients while reducing the cost of patients' medication.

The development of small molecule drugs targeting RNA has achieved initial results. In 2020, the world's first oral small molecule drug Risdiplam for the treatment of spinal muscular atrophy (SMA) was approved for marketing. According to Roche's financial report, in 2023, Risdiplam's global sales will reach 1.419 billion Swiss francs (nearly 1.6 billion US dollars). This has boosted the confidence of many people.

However, compared with the increasingly mature protein targeting field, how to quickly establish a research and development paradigm in the RNA targeting field is still a major challenge. Since the structural specificity of similar functional RNAs is not high and unstable, it is quite difficult to directly find drug molecules that meet the conditions and can bind to RNA.

The development of AI has provided new opportunities for target discovery and drug development. Xili Technology has developed the AI ​​computing platform VoyageR based on its own data. The platform mainly includes a target discovery platform and a drug discovery platform. The former is used to help realize RNA structure calculation and evaluation, and target function prediction, while the latter focuses on building compound libraries, molecular prediction, and molecular generation.

With the help of VoyageR, Xili can quickly complete the construction and expansion of the RNA-targeted small molecule library, combine high-throughput screening + AI + automated experimental verification of the dry and wet closed loop, and quickly obtain preclinical candidate compounds, greatly reducing costs, shortening the R&D cycle, and improving the success rate of drug development.

It is reported that, so far, more than 100 highly druggable targets have been screened with the assistance of VoyageR. Further verification and research are in progress. But this is only the front-end foundation. Unlike platform companies, the core goal of Xili Technology is to advance its own pipeline.

Li Yang told 36Kr that based on the principle of "product market fit", combined with the team's strengths and the current status of disease treatment in various fields, Xili is currently focusing on central nervous system-related diseases because "large molecule drugs are difficult to break through the blood-brain barrier, while small molecule drugs have advantages in this regard."

Through self-development and cooperation, Xili has established pipelines for multiple neurological diseases including Charcot-Marie-Tooth Disease, ALS, and cerebellar ataxia. Among them, the fastest-growing pipeline is the self-developed pipeline for Huntington's disease.

Huntington's disease is an autosomal dominant hereditary neurodegenerative disease caused by the expansion of the CAG-CAA repeats encoding polyglutamine in the Huntington (HTT) gene, and is characterized by chronic progressive chorea, cognitive dysfunction, and mental and behavioral abnormalities. Current therapies can only alleviate symptoms but cannot slow the progression of the disease.

Li Yang introduced that by allowing small molecules to bind to the mRNA precursor that expresses the mutant huntingtin protein, changing the mRNA splicing process and achieving its degradation, the drug under development by Xili can reduce the mutant huntingtin protein and delay or block the disease progression at the genetic level. The drug is expected to start Phase I clinical trials in 2025.

In addition, Xili Technology's amyotrophic lateral sclerosis (ALS) pipeline is currently making considerable progress, and has established a cooperative relationship with Cai Lei, a well-known ALS patient, and his team. It is expected to apply for IND and conduct Phase I clinical trials in early 2025.

Future commercialization will also focus on the authorization of core pipelines and the development of cooperative research and development with large pharmaceutical companies, so as to expand the research coverage while obtaining financial support. In the long run, Xili Technology hopes to promote the launch of self-developed drugs. Li Yang believes that the field of RNA-targeted small molecule drug development has great potential because "in addition to what we are doing, there are many other new mechanisms that can be developed into drugs. New breakthroughs continue to emerge, and this field is still very 'sexy'."