Research and development progress of the Company (as of April 2024)

ONE. Pharmaceutical industry

1. General situation of R&D

Adhering to the corporate philosophy of "scientific research as the basis and patient as the center", the company has deeply cultivated the field of cancer and chronic disease treatment, continued to increase R&D investment, continuously enriched the layout of innovative drug R&D pipeline, strengthened the construction of innovative R&D ecosystem and technology platform, actively promoted the progress of clinical trials, and achieved a number of major stage results. Up to the release of this report, the total number of pharmaceutical research projects is 111, including 73 innovative products and biosimilar projects. In 2023, the company's R&D investment (excluding equity investment) in the pharmaceutical industry was 2.293 billion yuan, an increase of 23.67%, of which the direct R&D expenditure was 1.60 billion yuan, an increase of 33.74%, and the proportion of direct R&D expenditure in the pharmaceutical industry revenue was 13.10%. Research and development work mainly includes the following aspects:

(1) Continue to implement the new drug research and development model combined with independent research and development, cooperative development and authorized product introduction (License-in), track the latest international drug mechanism and target as well as clinical application research progress, accelerate the layout of innovative drugs and the introduction of innovative drug projects at home and abroad, and clarify the project initiation criteria for innovative, differentiated and iterative innovation. Strengthen independent innovation research and development capabilities;

(2) Adhere to the differentiated research and development strategy, take the unmet clinical needs of patients around the world as the guidance, and take "clinical value, pharmacoeconomic value, commercial value" as the starting point, focusing on the endocrine, autoimmune and tumor three areas of the layout of a number of innovative products;

(3) Focus on clinically superior varieties and specialty special drugs, and accelerate the research and development layout of high technical barriers generic drugs and improved new drugs;

(4) To establish and form the industrial chain advantage of "API + preparation" of general generic drugs, develop technological improvement and innovation of external preparations, and strengthen market competitiveness;

(5) Strengthen the comprehensive dynamic evaluation of varieties under research, strengthen the management of introduced projects, especially clinical projects, accelerate the speed and quality of clinical development, especially clinical phase III projects, and accelerate the process of launching innovative drugs through prioritization of research projects and reasonable allocation of R&D resources;

(6) Establish a global R&D ecosystem for East China Pharmaceutical ADC through the layout of differentiated peptide innovation technology platform, immune disease antibody technology platform, microbial fermentation cytotoxin technology platform and innovative linker and coupling technology platform for win-win cooperation.

2. Overview of innovative R&D system and pipeline

The company has set up a whole chain of high-level talents and has an international vision, lean and efficient core R & D team, the existing R & D personnel of more than 1700 people, the establishment of a relatively complete R & D management system, covering the whole process of drug development from target research, early drug discovery, preclinical research, clinical trials to the registration and listing of new drugs.

The company's innovative research and development focus on the layout of endocrine, autoimmune and tumor three areas, the current innovative product pipeline has more than 60 items. With the continuous enrichment of the product pipeline, the company has continued to expand its innovative drug field to include more types of drug research and development, including small molecule drugs, polypeptide drugs, antibody drug conjugate (ADC), bispecic or multispecific antibody drugs, as well as the exploration of innovative therapies for endocrine, autoimmune and tumor diseases.

3. Research and development progress of innovative drugs, innovative medical devices and biosimilar drugs

Oncology field

The company strives to build a global leading platform for innovative cancer drug research and development. Through the discovery, screening and verification of new targets in drug pre-development, the company has established more than 30 innovative cancer drug products covering targeted small molecule drugs, ADCs, antibodies and PROTAC.

The company introduced the world's first ADC drug Somituximab injection (ELAHERE®, R&D code: The Chinese marketing authorization application for IMGN853 and HDM2002 was accepted in October 2023 for the treatment of platinum-resistant adult patients with folate receptor alpha (FRα) positive epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who have previously received 1-3 line systemic therapy. The product has been included in the CDE priority review in July 2023. In April 2024, the company was approved to join the international multi-center PSOC (platinum-sensitive Ovarian Cancer) Phase III clinical study to promote the front-line treatment of ovarian cancer with this product. In combination with beizumab, maintenance therapy for folate receptor alpha (FRα) -positive recurrent platinum-sensitive epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer in adults who have not developed disease progression after second-line platinum-containing chemotherapy. The product has been implemented in Hainan Boao Lecheng Pilot Zone in July 2023, and in August 2023, Hainan Boao Ruijin Hospital officially launched its real-world research for platinum-resistant ovarian cancer. In addition, in March 2024, the company's U.S. partners announced that ELAHERE® had moved from accelerated approval to full approval in the United States.

The Company's new Class 1 drug, Maivatinib tablets, was included in the breakthrough therapy category by CDE in May 2023 for advanced non-small cell lung cancer with rare EGFR mutations. In addition, the Phase III clinical trial of Maivatinib tablets in advanced non-small cell lung cancer with EGFR-sensitive mutations has successfully met its primary endpoint, and the company expects to file a marketing application for Maivatinib tablets with first-line EGFR-sensitive mutations in 2024.

The company's first self-developed ADC project HDM2005, intended to be developed for the treatment of advanced solid tumors and hematoma, has been submitted to China IND application in March 2024 and accepted.

The company's first fully self-developed small molecule anti-tumor drug, the first fully self-developed HPK-1 PROTAC (hematopoietic prokinase 1 protein degradation targeting chimera) drug HDM2006 has entered the IND research stage, intended to be used for advanced solid tumors and hematoma monotherapy and combination therapy, is expected to be submitted by the end of 2024 IND application.

In 2024, it is expected that three tumor independent innovation products will be confirmed by the PCC, while two self-developed products will be declared IND.

Endocrine field

With the GLP-1 target as the core, the company has created the world's leading platform for innovative diabetes drug research and development. At present, the company has established a pipeline of 6 under research and marketed products covering oral, injectable and other dosage forms, including a combination of long-acting, single-target and multi-target global innovative drugs and biosimilars. Based on the advantages of the existing pipeline, the company will continue to explore innovative projects related to GLP-1 targets, expand indications related to weight loss, lipid-lowering, NASH, heart failure, and continue to develop innovative drugs with higher drug delivery compliance and more clinical advantages.

The company's self-developed oral small molecule GLP-1 receptor agonist HDM1002 diabetes indication has been approved by the Sino-US double IND in May 2023, and achieved the first human trial (FIH) first subject medication in early June 2023. The Chinese IND application for weight management indications in overweight or obese people has been approved in September 2023. At present, the product has completed the Chinese SAD test and MAD test, and has started the phase II clinical study. Up to now, there are no oral small molecule GLP-1 receptor agonist drugs on the market in the world, HDM1002 will further enrich the company's product pipeline in the field of endocrine therapy, accelerate the company's integration into the global innovative pharmaceutical industry, and further enhance the company's comprehensive competitiveness.

The Chinese IND application for GLP-1R/GIPR double-target long-action polypeptide agonist HDM1005 for weight management in overweight or obese people and type 2 diabetes was approved in March 2024, and the first subject enrollment and administration of Phase Ia clinical study in China was completed in March 2024. In addition, the company has filed a U.S. IND application for the product's obesity or overweight indication in March 2024. In addition, a U.S. IND application for HDM1005 for overweight or obesity indications was approved in April 2024;

The multi-agonist DR10624 of FGF21R/GCGR/GLP-1R target under development by the holding subsidiary, Dowell Biological, has completed the Phase I single dose increment (SAD) study in China and the Phase I SAD study in New Zealand, and is currently carrying out the phase I b/ II a clinical trial of obesity combined with hypertriglyceridemia in New Zealand. It is expected to be completed by the end of 2024.

Liraglutide injection was approved for marketing by NMPA in March 2023 for diabetes and NMPA in June 2023 for obesity or overweight.

The diabetes indication of Simeaglutide injection has completed the enrollment of all subjects in the phase III clinical study, and the primary endpoint data is expected to be obtained in 2024 Q4.

At present, Degu Insulin injection has completed the enrollment of all subjects in the phase III clinical study, and the primary endpoint data is expected to be obtained in 2024 Q4.

Autoimmune field

The company has more than 10 innovative products of biological drugs and small molecules in the field of self-immune diseases.

ARCALYST® for injection, a global innovative product introduced by the company from Kiniksa in the United States, was listed in the "List of Clinically Urgent Foreign New Drugs (the first batch)" by CDE in China for the treatment of cold-pyrine-related periodic syndrome (CAPS); The China marketing authorization application for the CAPS indication was accepted in November 2023 and included in the priority review in January 2023. In addition, in September 2023, the "Second batch of Rare Diseases Catalogue" jointly issued by the National Health Commission and other departments included recurrent pericarditis (RP); In March 2024, the China marketing authorization application for the Linasep RP indication for injection was also accepted and has been included in the priority review in December 2023.

The marketing authorization application for ulinumab biosimilar HDM3001 (QX001S) was accepted by the NMPA in August 2023 for the treatment of plaque psoriasis.

The IND application for HDM3002 (PRV-3279), an innovative drug for the treatment of systemic lupus erythematosus, was approved by the CDE in April 2023 for admission to the Phase IIa MRCT trial (PREVAIL-2).

In 2023, the company introduced a series of topical preparations for skin disease indications, including Zoryve® (Roflumast cream and Roflumast foam) from Arcutis in the United States for the treatment of plaque psoriasis, atopic dermatitis, seborrheic dermatitis and psoriasis of the scalp and body; Wynzora® cream introduced from MC2 for the treatment of plaque psoriasis. The relevant clinical registration work is being actively promoted.

Innovative medical devices

HD-NP-102 (Glomerular Filtration Rate Dynamic Monitoring System and Remet Pyrazine Injection) : Company association with MediBeacon,Inc. The jointly developed glomerular filtration Rate Dynamic Monitoring System (" Dynamic Monitoring System ") and Ramepizide injection non-invasively monitor the fluorescence of ramepizide over time by intravenous administration and continuously measure glomerular filtration rate (GFR) in patients with normal or impaired renal function. According to the requirements of Chinese registration regulations, Rumei pyrazine injection and dynamic monitoring system need to be declared and registered according to the drug and medical device respectively. In November 2021, the dynamic monitoring system was approved to enter the special review procedure for innovative medical devices in China. In July 2022, the NMPA officially accepted the application for medical device registration of the dynamic monitoring system, which is currently in the review stage. The marketing authorization application for Remepizide injection, an innovative drug used in conjunction with the system, was accepted in China in January 2024. In addition, the MediBeacon® glomerular filtration Rate Dynamic monitoring system, which includes Remet pyrazine injection and dynamic monitoring system, has been recognized by the US FDA as a device-based combination product, after MediBeacon submitted a marketing application to the FDA and officially accepted in July 2023.

Figure: Pipeline map of major innovative products and biosimilars as of the release of the report

TWO. Registration and listing progress of domestic medical and beauty products

(More research and development progress, please pay attention to "huadong Pharmaceutical Co., LTD." & "huadong Pharmaceutical Investor Relations Management" public number)