On September 21, 2022, Chia Tai Tianqing Pharmaceutical, a subsidiary of China Biopharmaceuticals (01177.HK), signed an agreement with French biopharmaceutical company Inventiva at a price of US$307 million The patented compound, lanifibranor, was developed and commercialized for the treatment of non-alcoholic steatohepatitis (NASH) and other underlying metabolic diseases in China. Chia Tai Tianqing will pay an upfront payment of $12 million, and Inventiva is expected to receive an additional $5 million in the near term if certain clinical milestones are met. Additionally, under the terms of the agreement, Inventiva is expected to receive clinical, regulatory and commercial milestone payments totaling up to $290 million, as well as tiered royalties based on net sales.
01
Non-alcoholic steatohepatitis (NASH)—the new liver killer
Non-alcoholic steatohepatitis is a progressive chronic liver disease, also known as metabolic steatohepatitis. Its pathological changes are similar to alcoholic hepatitis, but the patient has no history of excessive drinking. , occurs in overweight and obese individuals, and can be life-threatening in severe cases. The precursor to nonalcoholic steatohepatitis is non-alcoholic fatty liver disease (NAFLD), a condition in which excess fat accumulates in the liver. As fat continues to accumulate in liver cells and the metabolic environment changes, liver cells become inflamed (swelling of the liver) and damaged, resulting in scarring of liver tissue (fibrosis), which in severe cases can lead to cirrhosis, liver failure, or hepatocellular carcinoma .
The diagnosis of NASH is extremely difficult, not only because patients often present with asymptomatic or only atypical NASH symptoms, but also because the risky and technically limited invasive puncture of the liver can only be performed diagnosis. Therefore, patients with NASH often do not seek reversal until the disease progresses to an advanced stage, but usually it is too late and the only option is liver transplantation, which is also the reason for the increasing number of liver transplants caused by NASH. However, there are many complications after liver transplantation, and it can take a long time to get a liver donor.
Figure 1 Transformation of NASH lesions at various stages (Source: Inventiva official website)
While viral and alcoholic hepatitis continue to be a major concern for liver disease worldwide, the prevalence of nonalcoholic fatty liver disease has jumped to the western level in the past few decades The country ranks first in liver disease, while the prevalence of other chronic liver diseases is stable and declining. According to statistics, there are currently 444 million NASH patients in the world. In 2016, there were about 32.8 million NASH patients in China, and it is expected that in 2030, the number will reach 48 million. At present, there is no officially approved treatment plan in China or abroad. Currently, a total of 5 NASH treatment drugs in the world have entered clinical phase III. Among them, only Lanifibranor and semaglutide of Denmark’s Novo Nordisk are or plan to launch clinical phase III in China in the near future. The cooperation between Sino Biopharmaceuticals and Inventiva is expected to bring the first approved NASH oral drug to the domestic market.
02
Liver health faucet layout NASH new territory
Sino Biopharmaceuticals is a medical branch of Chia Tai Group, and its subsidiary Chia Tai Tianqing, as a leading enterprise of “liver health” drugs in China, has been focusing on the research and development of liver disease drugs since the 1980s. , is committed to providing patients with efficient, safe and economical drugs to control the onset of liver disease in two categories: liver protection and enzyme reduction and antiviral infection. More than 30 years of persistence have made the market share in the field of liver disease reach 25% in the country. In 1988, Chia Tai Tianqing cooperated with scientific research units and launched the company’s first liver disease treatment drug – Qiangli Ning. In 2005, Magnesium Isoglycyrrhizinate Injection Tianqingganmei, known as “artemisinin in the field of liver disease”, was launched on the market, becoming the world’s first trans-isomer glycyrrhizate with more than 99% pure, and the compound patent even won the Chinese Patent Gold Award. In 2010, the generic drug Entecavir Runzhong was launched, accumulatively allowing more than 3 million chronic hepatitis B patients to enjoy the same curative effect as the original drug at a relatively high cost performance. In 2017, a new generation of antiviral drug Qingzhong (tenofovir dipivoxil) was launched. It is the only generic drug in China that has conducted a 5-year “head-to-head” controlled trial with the original product, and it is also the first anti-HBV drug approved in the EU in China. drug. In addition to the field of liver disease, Chia Tai Tianqing has also formed a strong product cluster in the fields of tumor, respiratory, infection, endocrine and cardiovascular and cerebrovascular.
This collaboration with Inventiva is another demonstration of Sino Biopharma’s pursuit of innovative breakthroughs in its core therapeutic area of liver disease. Xie Qirun, chairman of Sino Biopharmaceuticals, said: “For more than a decade, we have been at the forefront of helping China eliminate hepatitis B, and now NASH is the fastest growing cause of liver transplantation and liver cancer, but NASH has not yet Any approved treatment. We are delighted to enter into this agreement with Inventiva, which is a great opportunity to bring NASH treatments to China.”
Picture 2 Chairman of the Board of Directors and Executive Director of Sino Biopharmaceuticals: Ms. Xie Qirun (Source: Sino Biopharmaceuticals official website)
Lanifibranor, which received the glaucoma from China Biopharmaceuticals, is the most promising orally available small molecule among Inventiva’s drug candidates for the treatment of NASH. Lanifibranor is a peroxisome proliferator-activated receptor (PP)AR) agonists that induce anti-fibrotic, anti-inflammatory and beneficial vascular and metabolic changes in vivo by activating all three subtypes of PPAR, thus potentially addressing all key features of NASH: inflammation, steatosis, swelling and most importantly fibrosis. In a recent phase IIb trial, lanifibranor has demonstrated an effect on both resolution of NASH and fibrosis. While there are other PPAR agonists that activate only one or two PPAR isoforms, lanifibranor is the most advanced pan-PPAR agonist in clinical development for the treatment of NASH. Inventiva believes that the moderate and balanced pan-PPAR binding profile of lanifibranor contributes to the well-tolerated profile observed to date in clinical trials and preclinical studies. Currently, lanifibranor has received FDA Breakthrough Therapy designation and Fast Track designation for the treatment of NASH.
According to the agreement, all costs of lanifibranor’s trials in China will be borne by Chia Tai Tianqing. Various factors will determine whether Chia Tai Tianqing joins the ongoing NATiV3 phase III clinical trial of lanifibranor or Conduct independent research. Sean Chen, chief strategy officer of Sino Biopharmaceuticals, said that he is very optimistic about this cooperation. lanifibranor has the potential of best-in-class. He believes that it will help Sino Biopharmaceutical to further enrich its innovation pipeline in liver disease and consolidate its leadership in this therapeutic field. .
However, China Biopharma’s layout of NASH is not limited to PPAR targets. Through self-research and authorized introduction, it has comprehensively covered the proof-of-concept including FXR, THR-β, etc. Small molecule drug targets and macromolecular drug targets such as GLP-1 and FGF-21. It can be seen that Sino Biopharmaceutical has far-reaching plans to further expand its market share and continue to maintain its leading position in the field of liver disease.
Writing|Feng Lixiao
Typesetting|Feng Lixiao
References:
[1]https:https://www.globenewswire.com/news-release/2022/09/21/2520615/0/en/Inventiva-and-Sino-Biopharm-announce -licensing-and-collaboration-agreement-to-develop-and-commercialize-lanifibranor-in-Greater-China.html
[2]https:https://www.cn-healthcare.com/article/20200317/content-532777.html
[3]https:https://inventivapharma.com/therapeutic-areas/non-alcoholic-steatohepatitis-nash/
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