In 2018, a record high of over 100 Investigational New Drug Applications were handled by the state drug administration. 57 Class-I Chinese innovative drugs had filed the Investigational New Drug Application by mid-2019, showing a strong momentum.

1. Class-I Investigational New Drug Applications submitted in the first half of 2019

In the first half of 2019, about 57 Class-I Chinese new drugs filed the Investigational New Drug Application (domestically produced drugs), and the overall development of innovative varieties is on the increase. In the first half of the year, January is the month with the largest number of registered applications, with 16 varieties entering the IND stage.

Enterprises that have filed a relatively large number of applications (≥4) are CSPC and Chiatai Tianqing, while the other enterprises filed an average 1-2 applications. It is worth noting that Suzhou displayed a passion for the registration of new drugs. Zelgen, Ascentage, Sinovent, Teligene and Kintor in the Suzhou area have filed an average 1-2 applications.

Figure 1: Domestic INDs from January to June 2019

2. CSPC & Chiatai Tianqing (≥4)

☆ CSPC

In addition to the star variety of butylphthalide, CSPC’s antibody drug conjugate ADC (DP303C) and humanized gap junction protein 43 monoclonal antibody (ALMB-0166) have obtained the orphan drugs certification from the US FDA and the company has launched new drug clinical trials. Its L-amlodipine maleate has filed the New Drug Application in the US, which showcases its strength in new drug development.

In China, CSPC’s follow-up innovative varieties continued to show great potential in the first half of 2019, placing the company in the first spot in terms domestic new drug registration with 5 Class-I new drugs. The five varieties are SYHA1402 tablets, SYHA136 tablets, SYHA1803 capsules, SYHA1807 capsules and SYHA1801 capsules in chronological order.

Figure 2: CSPC’s Central Pharmaceutical Research Institute

☆ ~ Chiatai Tianqing

Chiatai Tianqing has successfully marketed its Class-I new drugs magnesium isoglycyrrhizinate injection (Tianqing Ganmei) and androtinib. It is widely praised for its more than 50 innovative drug research projects. Its annual research and development costs exceed RMB 1 billion, making it one of the Chinese drug companies that invest heavily in innovative drug research.

In China, Chiatai Tianqing filed Investigational New Drug Applications for 4 of its products — TQB3562, TQA3563, TQB3804 and TQC3564 tablets — in the first half of 2019.

Figure 3: Chiatai Tianqing Innovative Drug Research and Production Base

3. Chinese IND Varieties in the first half of 2019

For various reasons, the registration of most IND varieties is kept confidential. Some varieties have not yet been clinically tested and little information is disclosed about them. The information about the following ten varieties has been found available online.

☆~TERN-101

TERN-101, originally developed by Eli Lilly and Company, is a highly effective non-bile acid FXR agonist for the treatment of nonalcoholic steatohepatitis. In 2018, Terns signed a cooperation agreement with Eli Lilly and Company, obtaining the right to the global development, production and commercialization of TERN-101 for treating NASH. In April 2019, Terns presented preclinical data at EASL’s International Hepatology Conference held in Vienna, proving that TERN-101 can reduce liver steatosis, inflammation and liver fibrosis in diet-induced NASH model of obese mice. In the same month, NMPA accepted the application for clinical trial of this product. In June 2019, Terns started a Phase-I clinical trial of FXR agonist TERN-101 to further support the clinical research of TERN-101 in treating NASH.

☆~AST-3424

AST-3424 is a first-in-class anti-cancer drug jointly developed by Ascentawits and Taiwan-based OBI, which targets ornithine decarboxylase AKR1C3. AST-3424 can selectively release potent DNA alkylating agent under the action of AKR1C3 to initiate the mechanism for killing cancer cells.  This selective activation mechanism helps AKR1C3 play a crucial role in various drug-resistant and refractory cancers, such as liver cancer, castration resistant prostate cancer, T cell acute lymphoblastic leukemia and other tumor cells. Taiwan-based OBI is currently conducting Phase-I and Phase-II clinical studies in the United States to treat solid tumors. In July 2018, OBI-3424 obtained the orphan drugs certification from FDA. In April 2019, NMPA processed the application for clinical trial of this product.

☆~TSL-0319

TSL-0319 capsule is a dipeptidyl peptidase 4(DPP-4) inhibitor independently developed by Tasly. It can inhibit the inactivation of glucagon-like peptide -1(GLP-1) and glucose-dependent insulin secretagogue polypeptide (GIP), promote the release of insulin from islets of Langerhans, thus improving the insulin level and achieving the purpose of reducing blood sugar. This drug is a fully proprietary, innovative new Class-I chemical drug, yet to be marketed in China’s market and foreign markets. So far, this project has received an R&D investment of RMB 16.95 million.

☆ ~ LH021 injection

LH021, a disease-alleviating drug, has the potential to repair damaged knee joint cartilage. In 2015-2016, the mechanism research was completed; in May 2016, the project was officially approved; in June 2016, the CMC was started; in December 2016, it applied for a domestic patent; in June 2017, the safety assessment study was started; in September 2018, the IND PACKAGE was officially completed; in October 2018, the pre-IND meeting was held; in January 2019, an Investigational New Drug Application was filed; in March 2019, the application was officially processed. The design of the clinical trial plan will be mainly based on the clinical research on foreign DMOAD drugs. Drawing on the clinical trial experience of similar products at home and abroad, the subjects of the first Phase-I clinical trial of LH021 in human bodies will be patients with primary knee osteoarthritis who meet the selection criteria, instead of healthy subjects. In Phase-I clinical trial, in addition to the tolerance and pharmacokinetic characteristics of rising Lh021 dosage, the relationship between LH021 dose and efficacy and between cartilage synthesis and metabolism related biomarkers will also be explored to provide basis for the formulation of Phase-II clinical trial drug delivery scheme. In the first human clinical trial, incremental drug administration that combines single and multiple doses will be applied to treat primary knee osteoarthritis. The observation period will be 28 days after a single dose, and the follow-up visit will last 28 days after a cycle of multiple doses, with a total test period of 11 weeks.

☆~TTP273

TTP273 is a non-peptide, highly selective glucagon-like peptide -1 receptor (GLP-1R) agonist discovered by VTV using its small molecule drug research and development platform. It is VTV’s first-in-class. The related Phase-IIB clinical research has been completed in the United States. Results show that TTP273 can significantly reduce the level of glycosylated hemoglobin in diabetic patients and is well tolerated. The predominant feature and highlight of the TTP273 project are that GLP-1 and its analogues currently on the market are injections, while the TTP273 product is the first small molecule non-peptide oral preparation. Through licensing, Huadong Medicine introduced the TTP273 project as a complement to its GLP-1 diabetes product line. It’s complementary to the current Liraglutide injection under research.

☆~101BHG-D01

101BHG-D01 is a Class-I new drug developed by Beijing-based Showby Pharma for the treatment of asthma/COPD. Showby Pharma was established through financing and regrouping in 2016 on the basis of Beijing Fengshuo Weikang Technology Development Co., Ltd. (established in 2001) and Beijing Jiashi Lianbo Pharmaceutical Technology Co., Ltd. (established in 2007). The company has an R&D team of 40 people, and its core team has over 30 years of experience in new drug research and development. It is divided into the Pharmacy Department, the Clinical Medicine Department, the Administration and Human Resources Department, and the Intellectual Property Department. Its main business is innovative drug research and development.

☆~LH021

Lh021 is a Class-I new drug independently developed by Guangzhou-based Link Health for the treatment of osteoarthritis. Link Health, established in 2012, is engaged in the research and development of innovative green fluorescent protein drugs. The company was founded by Chinese who have studied overseas and domestic elites in the pharmaceutical industry. Its R&D undertakings include 12 new drug projects, covering major chronic diseases such as tumors and digestive diseases and aging related diseases.

☆~GST-HG151

Developed by Fujian Cosunter in cooperation with Shanghai-based WuXi AppTec, GST-HG151 is a drug for reversing non-alcoholic fatty liver disease and liver fibrosis. Preclinical research has confirmed its role to improve liver function and to remarkably resist fibrosis. It’s on track to fill the gap in combating fibrosis and overcome irreversible liver fibrosis and cirrhosis that have haunted the world for long.

☆~LX-039

LX-039 is a Class-I new drug developed by Shandong-based Luoxin Pharmaceutical for the treatment of breast cancer. The oral drug is a new, effective selective estrogen receptor antagonist mainly used for the treatment of advanced breast cancer. No oral drugs providing the same mechanism have come on China’s market and foreign markets. Similar products are in Phase-I and Phase-II clinical trials.

☆~YPS345

YPS345 is a Class-I new drug jointly developed by Topfond and the Institute of Biophysics of the Chinese Academy of Sciences for the treatment of pneumonia and pulmonary fibrosis caused by chest radiotherapy in tumor patients. Currently, there are no similar products in the market. Topfond’s effectiveness and safety research on YPS345 in non-clinical trials show that, as a drug for preventing and treating radioactive inflammation, it can safely and significantly relieve lung fibrosis induced by radiotherapy and chemotherapy in animal models.

☆~CS3003

CS3003, an HDAC6 selective inhibitor developed by Cstone Pharmaceuticals, can be used as single drug therapy or combined with conventional standard therapy, and has the potential to show better curative effect in multiple myeloma. Preclinical research and the preclinical and early clinical studies of similar products indicate that CS3003 is safer than broad-spectrum HDAC inhibitors and can potentially be used together with immune checkpoint inhibitors to treat different indications.

☆~ASC21

ASC21, developed by Ascletis, is a nucleotide inhibitor that binds to NS5B polymerase to prevent chronic hepatitis C virus infection by inhibiting the activity of NS5B polymerase. Preclinical studies have shown that ASC21 is an effective pan-genotype drug with a high resistance gene barrier. Ascletis plans to combine it with Ravidasvir to treat refractory cirrhosis and HCV/HIV coinfection patients.

Table: Chinese Class-I New Drug INDs from January to June 2019