Cargene Biopharma Advances siRNA-Based Liver Regeneration Therapy for Late-Stage Liver Disease

China and Asia bear an exceptionally heavy burden of liver diseases. In recent years, an increasing number of companies in China have been entering the field of liver diseases, bringing innovative therapies to the global stage. CARGENE BIOPHARMA, a nucleic acid drug company that emerged from stealth mode in 2021, is one of them.CARGENE BIOPHARMA is committed to developing the world's first innovative target for restoring liver regeneration capabilities, with the CG-LR1 candidate in the preclinical research stage and a pipeline layout targeting a series of innovative liver regeneration targets.

CG-LR1 is a new target for inhibiting liver cell regeneration,Expected to file IND in 2024`, with First-in-Class potential`, discovered by the groundbreaking in vivo functional genomics platform of CARGENE BIOPHARMA's scientific founder, Professor Torsten Wuestefeld. Torsten Wuestefeld is a pioneer in the field of liver regeneration, dedicated to overcoming liver fibrosis through mechanisms of liver regeneration.

The main treatment for advanced liver disease is currently liver transplantation, which has a huge unmet need.CARGENE BIOPHARMA is one of the few companies focusing on functional liver regeneration as a drug research and development direction. Leveraging the characteristic of siRNA having no undruggable targets, CARGENE BIOPHARMA is unfolding a new landscape for liver disease treatment.

Recently, VCBeat interviewed Kathy He, the CEO of CARGENE BIOPHARMA.

CARGENE BIOPHARMA was incubated by EVX Ventures, which is dedicated to creating and incubating biopharmaceutical enterprises globally. Targeting disruptive platform technologies and novel therapeutic approaches, EVX has successfully incubated multiple companies in China, the United States, and Singapore.

Initially, CARGENE BIOPHARMA's R&D team was based in Singapore. However, the value release of innovative therapies relies on global resources, and undoubtedly, the two most important coordinates in the global market are China and the United States. Therefore, in June 2022, CARGENE BIOPHARMA invited Ms. Kathy He (He Qizhi), who has over 20 years of experience in the pharmaceutical industries of both China and the U.S., to join as the Chief Executive Officer.

Kathy has been responsible for the R&D and market promotion of several blockbuster drugs from MNCs such as Takeda, Merck, and Abbott in the United States. She also has extensive experience in cross-border investment between China and the U.S. and Biotech entrepreneurship, witnessing the development of China's innovative drug industry.As the dividends of China's Me-too and Fast-follow approaches gradually disappear, Kathy He believes that Biotechs with original innovation capabilities, returning to the essence of innovative drugs, will become the leaders of the next generation. CARGENE BIOPHARMA, with its unique biological insights and siRNA technology platform, holds tremendous potential.

CARGENE BIOPHARMA CEO Kathy He

"The key to the success of innovative drugs lies in two aspects: one is the innovative target based on biological insights, and the other is the technical means to intervene in the innovative target. As a new technical approach without 'undruggable' targets, siRNA has been validated by multiple marketed drugs. Therefore, it is essential to develop differentiated products on this platform."Deep biological insights will become a competitive advantage.." Kathy He said.

CARGENE BIOPHARMA is developing siRNA products targeting novel pathways as well as extrahepatic delivery platforms, primarily focusing on treating various liver diseases by leveraging regenerative principles. These include fatty liver disease and fibrosis, cirrhosis, and liver dysfunction caused by various types of hepatitis. Notably, in the field of utilizing siRNA technology to target innovative pathways for restoring liver regenerative capacity,CARGENE BIOPHARMA is a pioneer at the forefront of the world.The company aims to leverage liver regeneration to promote liver function in patients with advanced liver disease, fibrosis, and cirrhosis, whose liver function is gradually deteriorating. For NASH patients with fibrosis, the company seeks to achieve, through its unique regenerative mechanism, what the industry has yet to accomplish: reducing or even reversing fibrosis.

The rapid rise of this young company is inseparable from its ability to integrate global resources in terms of talent, technology, and production capacity.Chief Scientific Officer Dr. Yann Chong Tan, a Stanford University graduate and serial entrepreneur with extensive experience in the biotechnology field, is a co-founder of Atreca and the founder of Nuevocor, as well as the inventor of multiple patents. The scientific advisory board includes Harvey Lodish, professor of biology and bioengineering at MIT and founding member of the Whitehead Institute for Biomedical Research; Torsten Wuestefeld, professor at the Genome Institute of Singapore; Stuart Forbes, professor at the University of Edinburgh and a pioneer in the field of liver regeneration; and Scott Friedman from the Icahn School of Medicine at Mount Sinai, a key discoverer of the mechanisms of liver fibrosis. These globally leading KOLs share a common aspiration:Successfully launched the world's first breakthrough therapy to enhance liver regeneration, addressing the unmet need for treatments in advanced liver disease.

CARGENE BIOPHARMA utilizes its proprietary GalNAc technology for liver-targeted delivery, integrating its exclusive siRNA screening, modification, and delivery platform along with the founding team's deep biological insights. The company is committed to innovating on targets, allowing for greater flexibility in patent development. According to reports, CARGENE BIOPHARMA’s liver-targeted delivery will also leverage the team’s expertise and advantages in CMC, including ensuring efficacy and safety while making synthesis more convenient and scalability easier.

CARGENE BIOPHARMA has two independently developed platforms: sequence screening and sequence modification. Its sequence screening platform is OSCAR. There are thousands of options for selecting silenced genes, but through the OSCAR algorithm, the genes that meet the requirements can be quickly identified to achieve the product's TPP.

"It only takes a few minutes for OSCAR to generate a series of gene results, and specific criteria such as safety and specificity are adjustable," Kathy introduced. "We are continuously optimizing the OSCAR algorithm with new data, and when we have sufficient data, OSCAR will be trained into an AI sequence screening platform."

CARGENE BIOPHARMA's sequence modification platform is the SMoP pharmacophore, a universally applicable modification model designed based on CARGENE BIOPHARMA's years of practical experience.After the OSCAR algorithm generates new nucleic acid sequences, they can be modified using the SMoP design pattern to meet the required lead profile standards for efficacy, safety, and other criteria. The seamless integration of OSCAR and SMoP, combined with their development platform, forms CARGENE BIOPHARMA's efficient nucleic acid design and drug discovery platform.

Moreover, targeting delivery beyond the liver is a research direction for many small nucleic acid Biotech companies, and the industry as a whole is still in the early stages of extrahepatic delivery. The first successful clinical entry in extrahepatic delivery was Alnylam's C16 platform, specifically optimized for delivery to CNS tissues. Based on its unique resources and technical advantages, CARGENE BIOPHARMA is now targeting ocular diseases and is conducting preclinical validation in the field of extrahepatic delivery.

"We maintain communication and cooperation with large pharmaceutical companies. They hope to obtain groundbreaking new products through our technology platform or gain insights in more cutting-edge fields like extrahepatic delivery. As a Biotech, we can leverage the clinical resources and advantages of large pharmaceutical companies to conduct clinical trials. CARGENE BIOPHARMA also has close cooperation with external clinical experts, ultimately aiming to validate innovative targets and identify the most suitable patient population."

The in vivo functional genomics platform from Professor Torsten Wuestefeld is one of CARGENE BIOPHARMA's core advantages and the source of the new target CG-LR1, which inhibits hepatocyte regeneration. Professor Torsten Wuestefeld has been deeply engaged in the field of regenerative medicine for many years. In 2013, he was the first to publish an article in Cell, revealing the therapeutic potential of the MKK4 target for hepatocyte regeneration through in vivo RNAi screening. His technical platform is widely recognized in the industry.

The principle of liver repair is to generate new healthy liver cells to ensure the functioning of the liver. However, many diseases reduce the regenerative capacity of liver cells. When the liver is damaged but cannot be repaired in time through regeneration, liver fibrosis occurs. Prolonged fibrosis leads to increasingly severe liver cell damage, eventually resulting in cirrhosis or liver cancer. Apart from liver transplantation, there are currently no effective treatments for advanced liver disease. The population of liver disease patients in Asia is vast, with a prevalence of non-alcoholic fatty liver disease (NAFLD) in Asia at approximately 29.6%. Among these, 25% of simple fatty liver disease cases progress to non-alcoholic steatohepatitis (NASH) or even cirrhosis. Globally, there are over 120 million patients with cirrhosis, and each year, 1% to 4% of cirrhosis patients may progress to hepatocellular carcinoma (HCC), indicating a significant unmet need for drugs. The development of medications for chronic liver diseases has always been challenging. Taking NASH as an example, after four decades of research challenges, there are currently over 200 NASH drug projects under development globally, with more than 100 projects in clinical development stages, but no first-in-class drug has yet been approved.

Therefore, the unique technical platform of Professor Torsten Wuestefeld, combined with the high efficiency of small nucleic acid delivery to hepatocytes, has made the strategic focus on advanced liver diseases an important strategy for CARGENE BIOPHARMA.

"In the next two to three years, CARGENE BIOPHARMA’s primary goal is to advance its existing pipeline and realize the value of its liver regeneration platform," Kathy introduced. "CG-LR1 has reached the PCC stage, and currently, the liver regeneration platform has generated a series of other targets. The company is internally evaluating and selecting the next target as well as the scope of indications."

CARGENE BIOPHARMA will soon announce the efficacy and safety data of CG-LR1 at the International Liver Congress, engage in in-depth exchanges with companies and medical institutions worldwide, and attract more external collaborations.CARGENE BIOPHARMA will continue to leverage small nucleic acid drugs to realize unique biological insights, bringing innovative and effective treatments to patients.