Sinopharm Giant Huadong Medicine Inks $1.5B Deal for IM19 CAR-T Therapy Within a Month

On the evening of August 4, 2024, Huadong Medicine Co., Ltd. announced that its wholly-owned subsidiary, Huadong Medicine (Hangzhou) Co., Ltd. ("Huadong Medicine"), signed an exclusive commercialization cooperation agreement with Beijing Yimiaoshenzhou Medical Techology Co., Ltd. ("Yimiao Shenzhou"). Huadong Medicine obtained the exclusive commercial rights in China for Yimiao Shenzhou's IM19 Chimeric Antigen Receptor T-cell Injection (referred to as "IM19 CAR-T Cell Injection"), a CD19-targeted autologous CAR-T candidate product. Huadong Medicine will pay Yimiao Shenzhou an upfront payment of RMB 125 million and registration and sales milestone payments of up to RMB 950 million.

 

According to the announcement, IM19 CAR-T cell injection has successively received clinical trial approval notices for three indications: relapsed/refractory diffuse large B-cell lymphoma (r/r-DLBCL), acute B lymphoblastic leukemia (B-ALL), and mantle cell lymphoma (MCL). All have now entered the registration clinical research phase. Among them, the study on end-stage treatment for diffuse large B-cell lymphoma is about to complete Phase II clinical trials (confirmatory clinical trial), with positive clinical efficacy and safety data. The application for marketing authorization is expected to be submitted in the fourth quarter of 2024.

IM19——Self-developed CAR-T Drug

CD19 is a surface protein expressed on B lymphocytes and follicular dendritic cells. It belongs to the immunoglobulin (Ig) superfamily, located on the short arm of chromosome 16 (16p11.2), encoding a type I transmembrane glycoprotein of 556 amino acids with a molecular weight of 95 kDa. CD19 regulates the development, proliferation, and differentiation of B cells through both B cell receptor (BCR)-dependent and -independent pathways. CD19, together with CD21, CD81, and CD225, forms the BCR complex, which lowers the threshold for BCR-mediated B-cell activation. Within this complex, CD21 provides a bridge to surface immunoglobulins, CD81 modulates the expression of CD19, and CD19 plays a key role in signal transduction. Currently, the main clinical approaches targeting CD19 for the treatment of malignant tumors are chimeric antigen receptor T-cell (CAR-T) therapy and antibody-drug conjugates (ADCs).

 

Currently, CD19 is the primary target for the development of B-cell derived hematological tumor drugs, but it is not expressed in the field of solid tumors. Globally, there is a desire to find a unique antigen similar to CD19 in the solid tumor field to serve as a target for CAR-T cell recognition. Once a suitable target is found, the technical difficulties in developing monoclonal antibodies, bispecific antibodies, ADCs, cellular drugs, and other technologies are expected to be resolved. Therefore, such a target has been referred to as an "internet-famous" target.

 

IM19 CAR-T Cell Injection (IM19 Chimeric Antigen Receptor T-Cell Injection) is the first CAR-T cell therapy product independently developed by Beijing Yimiaoshenzhou Medical Technology Co., Ltd. It has successively received clinical trial approval notices for three indications from the National Medical Products Administration: relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), acute B lymphoblastic leukemia (B-ALL), and mantle cell lymphoma (MCL). All have entered the registration clinical research stage.

 

Among them, the research on acute B lymphocytic leukemia and mantle cell lymphoma has completed the infusion for all subjects in Phase 1 and is about to enter Phase I clinical trials. In the future, Beijing Yimiaoshenzhou Medical Techology Co., Ltd. also plans to conduct clinical trials for second-line treatment of diffuse large B-cell lymphoma.

 

In December 2023, the joint research team composed of the Lymphoma Department of Peking University Cancer Hospital and Beijing Yimiaoshenzhou Medical Technology Co., Ltd. announced the key clinical research data from the Phase Ib/II study on IM19 CAR-T cell injection for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) at the 2023 ESMO Asia Congress. The results showed that as of the data cutoff date of June 15, 2023, among the 59 patients who had completed at least one efficacy assessment, the incidence rates of cytokine release syndrome (CRS) and neurotoxicity (NT) were 42% and 7%, respectively, with no patients experiencing grade 3-4 CRS or NT.

 

Data show that IM19 CAR-T cell injection demonstrates a high and sustained disease remission rate with a low incidence of severe adverse reactions in patients with relapsed or refractory B-NHL. As of now, among the patients evaluable for efficacy, the latest best overall response rate (BOR) for IM19 CAR-T cell injection is 76%.

 

In December 2023, the joint research team composed of the Department of Hematology at Peking University Third Hospital and Beijing Yimiaoshenzhou Medical Technology Co., Ltd. announced the latest results of the Phase I clinical study on IM19 CAR-T cell injection for the treatment of relapsed or refractory mantle cell lymphoma (MCL) at the 65th American Society of Hematology (ASH) Annual Meeting in 2023. The preliminary data from this Phase I clinical study indicate that IM19 CAR-T cell injection demonstrates a favorable objective response rate in patients with relapsed or refractory MCL, with a low incidence of severe CRS and neurological events.

 

In China, the number of newly diagnosed MCL patients accounts for approximately 3.5% of NHL, with about 3,100 new cases each year. Due to the still high recurrence rate of MCL and its highly aggressive nature after recurrence, there is a lack of effective treatment options in clinical practice. The IM19 CAR-T cell injection has demonstrated promising potential in terms of safety and efficacy for the treatment of MCL.

In Less Than a Month, "BD Maniac" Secures Another Collaboration Worth Over 1 Billion Yuan

For Huadong Medicine, which has introduced the IM19 CAR-T cell injection, the oncology field is one of its key strategic focus areas. This move has achieved a leading layout that covers both solid tumors and hematologic malignancies with a "multi-cancer type + multi-therapy" approach. It has already established a strong market service team in the field of hematological tumor cell therapy. Through this collaboration, both parties will leverage the leading product advantages of the IM19 injection and Huadong Medicine's robust commercialization capabilities to further accelerate the commercialization process of the IM19 injection in China, effectively meeting the significant clinical demand for B-cell hematologic malignancies in the country.

 

In fact, this is not the first time Huadong Medicine has reached a cooperation in the CAR-T field. In January 2023, it had reached a commercialization cooperation for the BCMA autologous CAR-T product with Coeus Pharmaceuticals.

 

In recent years, innovative drugs in fields such as cell therapy and ADC have become the most important areas of drug development for Huadong Medicine. According to publicly available information, Huadong Medicine currently has 111 ongoing research projects, of which 73 are innovative products and biosimilar projects. In its announcements, Huadong Medicine mentioned that it is making forward-looking and in-depth arrangements in several key strategic areas including ADC, GLP-1, autoimmune diseases, industrial microbiology, and medical aesthetics. Adhering to innovation-driven development as the main theme of its strategy, Huadong Medicine considers innovative drugs as the foundation and direction for building future core competitiveness. The company focuses on the layout and development of new products with significant clinical value in the fields of major diseases and chronic conditions.

 

This strategic focus on innovative drugs is also reflected in its financial report, which shows that in 2023, the company's pharmaceutical R&D investment (excluding equity investments) reached 2.293 billion yuan, a year-on-year increase of 23.67%. Of this, direct R&D expenditure amounted to 1.6 billion yuan, marking a year-on-year increase of 33.74%. The proportion of direct R&D expenditure to pharmaceutical revenue was 13.10%.

 

In addition, the fields that Huadong Medicine focuses on are not limited to innovative drugs. In the entire pharmaceuticals sector, Huadong Medicine is actively expanding and aggressively pursuing BD (Business Development).

 

According to incomplete statistics, between 2019 and 2021, Huadong Medicine completed nearly 20 BD deals in significant investments. Additionally, according to incomplete statistics from VCBeat New Medicine, from 2021 to 2024, Huadong Medicine engaged in a total of 13 external cooperation deals (excluding commercial promotion partnerships). The largest upfront payment in a License-in deal was for the collaboration on ADC drugs HDP-101 and HDP-103 with Heidelberg Pharma in 2022. Huadong Medicine will subscribe to the publicly issued shares of Heidelberg Pharma at a price of €6.44 per share and acquire part of the current equity from existing shareholders, including dievini fund. The total amount is €105 million, and Huadong Medicine will hold 35% of Heidelberg Pharma’s equity, becoming its second-largest shareholder.

 

Therefore, Huadong Medicine was once dubbed the "BD Maniac" by the industry.

 

This collaboration with Beijing Yimiaoshenzhou Medical Techology Co., Ltd. marks the third BD deal announced by Huadong Medicine within 30 days.

 

On July 15, Huadong Medicine announced that its wholly-owned subsidiary, Sinopharm-Zhongmei Huadong, signed a strategic cooperation agreement with Aozong Biotech to obtain exclusive rights for the development, registration, production, and commercialization of all indications of the improved new drug Edaravone oral formulation TTYP01 tablets (Edaravone tablets) in China. According to the terms of the agreement, Aozong Biotech will receive an upfront payment of 100 million RMB and milestone payments for development, registration, and sales totaling up to 1.185 billion RMB, including registration milestone payments and sales milestone payments not exceeding 400 million RMB and 785 million RMB respectively, as well as tiered royalties on net sales reaching up to double digits.

 

On July 21, Huadong Medicine announced that its wholly-owned subsidiary, Bohua Pharmaceutical, signed an "Agreement on the Acquisition of Equity in Guizhou Hengba Pharmaceutical Co., Ltd." with Hengba Pharmaceutical, He Xiaoling, He Yao, and others. Bohua Pharmaceutical acquired 100% of Hengba Pharmaceutical's equity at a base transaction price of 528.47 million yuan, with additional floating payments to be made according to the agreement. Through the acquisition of Hengba Pharmaceutical, Huadong Medicine will obtain exclusive products such as Shangkeling Spray and Tongbining Capsules, further enriching the company’s external preparation product pipeline and strengthening its core competitiveness in the field of external preparations.