CStone Pharmaceuticals completes the first patient enrollment in Phase I clinical trials in the United States for the treatment of advanced B-cell lymphoma and solid tumors

Wuhan Langlai P2X3 receptor selective antagonist QR052107B was approved for clinical treatment of chronic pain

On March 31, 2022, data from CDE’s official website showed that Wuhan Langlai’s QR052107B received the CDE’s implied clinical license, and the approved indication was chronic pain.

QR052107B is a P2X3 receptor selective antagonist independently developed by Wuhan Langli, which was originally developed for the treatment of refractory and/or unexplained chronic cough. P2X3 receptors are widely expressed on autonomic sensory nerves and are considered to be one of the core factors that induce cough and cough hypersensitivity. P2X3 receptor antagonists reduce afferent nerve excitability and suppress cough by antagonizing P2X3 receptors located in primary afferent nerves. Clinical studies have also demonstrated the effectiveness of P2X3 antagonists in the treatment of chronic cough. Basic studies have shown that non-selective P2X3 antagonists have obvious adverse effects of taste disturbance due to antagonizing P2X2/3 heterotrimers, and patients have poor compliance.

As a new generation of highly selective P2X3 antagonist, QR052107B can solve the adverse reactions of dysgeusia while maintaining the therapeutic efficacy, and has better safety. In addition, non-clinical studies have shown that QR052107B has a clear pharmacodynamic effect in animal pharmacodynamic models such as pain and itching. This clinical approval means that QR052107B has entered the research stage of multi-indication development.

Euho Pharma’s YH003 was granted an implied clinical license from CDE for the treatment of mucosal melanoma

On March 31, 2022, data from CDE’s official website showed that Euho Pharma’s CD40 monoclonal antibody YH003 was approved by CDE for clinical use. The indication is the treatment of unresectable/metastatic mucosal melanoma.

YH003 is a new humanized antibody that targets CD40, a member of the tumor necrosis factor receptor superfamily (TNFRSF) on the surface of immune cells, developed by Euho Pharma. By specifically activating the CD40 receptor signaling channel, it promotes the activation of innate immune cells such as dendritic antigen-presenting cells (DC), and positively regulates the effector activity of anti-tumor T cells. Studies to date have shown that CD40 activation is a key regulatory point in tumor immunotherapy, which can effectively convert cold tumors lacking immune cell infiltration into hot tumors that respond well to tumor immunotherapy.

In the preclinical antibody screening stage, Euho Pharma made full use of the tumor model in CD40 humanized mice independently developed by Biocytos, and quickly screened in mice to completely inhibit tumor growth without side effects such as hepatotoxicity. cloned antibodies. Whether used alone or in combination with anti-PD-1 monoclonal antibodies, YH003 has demonstrated strong anti-tumor effects on a variety of tumor models in mice. Pharmacodynamic studies in mice showed that YH003 significantly increased the proportion of anti-tumor T cells in tumor-infiltrating cells. Importantly, YH003 showed good safety even at very high doses, both in mice and monkeys.

CD40 (cluster of differentiation 40), expressed in APCs such as dendritic cells (DC), B cells, monocytes, as well as many non-immune cells and a wide range of tumors. The interaction of APC with its trimeric ligand CD154 on activated T helper cells results in the activation of APC, which mediates multiple functions including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. was found to be essential in various immune and inflammatory responses. Agonistic CD40 antibodies have been shown to activate APCs, promote antitumor T-cell responses, and culture cytotoxic myeloid cells, potentially controlling tumor growth in the absence of T-cell immunity. Agonistic CD40 antibodies have also been shown to activate tumor-killing macrophages and indirectly activate NK cells. Binding of CD40L to CD40 on endothelial cells stimulates the production of cytokines and chemokines and may promote tumor infiltration of immune cells such as T cells.

2clinical progress

CStone Pharmaceuticals completes the first patient enrollment in Phase I clinical trials in the United States for the treatment of advanced B-cell lymphoma and solid tumors

On March 31, 2022, CStone Pharmaceuticals announced that CS5001 has completed the first patient enrollment in the Phase I clinical trial in the United States. This international multicenter Phase I clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of CS5001 in advanced B-cell lymphoma and solid tumors.

CS5001 is a potential global “Best-in-class” ADC drug targeting ROR1. ROR1 is a typical tumor embryonic protein with low or no expression in adult tissues, but high expression in various tumors, including various leukemias, non-Hodgkin lymphomas, breast, lung and ovarian cancers . Preclinical data show that CS5001 exhibits strong selective cytotoxicity in multiple ROR1-expressing tumor cell lines and significant in vivo antitumor activity in both hematological and solid tumor xenograft mouse models.

As one of the fastest ROR1 ADCs in the world, CS5001 has been approved to start an international multi-center Phase I clinical trial (NCT05279300) in the United States and Australia, and its clinical trial application in China was also approved by CDE on March 3, 2022 Accepted. According to the statistics of Yaodu, CS5001 of CStone is the first ADC drug targeting ROR1 by a domestic company, and Zilvertamab vedotin developed by Merck and Velosbio is the one with the fastest progress.

On January 13, 2022, Merck R&D (China) Co., Ltd. obtained an implied clinical license from CDE for the treatment of diffuse large B-cell lymphoma (CXSL2101418).

CS5001 is a license in drug introduced by CStone from South Korea. On October 29, 2020, CStone announced that it has entered into a licensing agreement with LegoChem Biosciences, Inc. (LCB) for the development and commercialization of LCB71 (CS5001). Under the terms of the agreement, CStone will receive an exclusive license to lead the development and commercialization of LCB71 (CS5001) in other parts of the world outside of Korea; LCB will receive an upfront payment of US$10 million and up to US$353.5 million Milestone payments and additional tiered royalties.

3 Pharmaceutical deals

Chengdu Sunna and Aoda Bio have reached an agreement on the transfer of anti-coronavirus polypeptide drugs, with an estimated total investment of 175 million yuan

On March 31, 2022, Chengdu shengnuo Biotechnology Co., Ltd. announced that its wholly-owned subsidiary Chengdu shengnuo Biopharmaceutical Co., Ltd. intends to cooperate with Chengdu Aoda Biotechnology Co., Ltd. The joint research and development of the anti-coronavirus polypeptide drug project (AOD53724) with independent intellectual property rights and the global exclusive right to use the patent of this project enjoyed by Aoda Bio have reached a cooperation.

According to the terms of the agreement, Aoda Bio will transfer the clinical approval documents of its projects in China (so far, no clinical approval documents have been obtained) and all rights related to the patent rights to shengnuopharm. The technology transfer fee is RMB 65,000,000 (tax included), which will be paid in installments by shengnuo Pharma according to the progress of the target project agreed in the “Transfer Contract”.

There are currently different research and development stages of new crown prevention and treatment drugs in the world, and a number of new crown vaccines have been launched in China; after inquiries, as of the end of 2021, 4 domestic new crown vaccine products have been conditionally approved for marketing, 3 have been approved for emergency use, and another has been approved for emergency use. A number of drugs are in the clinical trial stage; at the same time, a number of antibody and small molecule drugs are also in different development stages. AOD53724 is in the preclinical animal efficacy safety evaluation test stage, and it is expected to apply for clinical approval in China by the end of 2022.

In order to ensure the smooth progress of the AOD53724 project, the company needs to pay the clinical trial fees for each phase according to the progress of the project. It is estimated that the completion of the AOD53724 project will take 2 to 3 years, and the total investment is expected to be about RMB 175 million before the product is commercialized.

CStone Pharmaceuticals completes the first patient enrollment in Phase I clinical trials in the United States for the treatment of advanced B-cell lymphoma and solid tumors

Wuhan Langlai P2X3 receptor selective antagonist QR052107B was approved for clinical treatment of chronic pain

On March 31, 2022, data from CDE’s official website showed that Wuhan Langlai’s QR052107B received the CDE’s implied clinical license, and the approved indication was chronic pain.

QR052107B is a P2X3 receptor selective antagonist independently developed by Wuhan Langli, which was originally developed for the treatment of refractory and/or unexplained chronic cough. P2X3 receptors are widely expressed on autonomic sensory nerves and are considered to be one of the core factors that induce cough and cough hypersensitivity. P2X3 receptor antagonists reduce afferent nerve excitability and suppress cough by antagonizing P2X3 receptors located in primary afferent nerves. Clinical studies have also demonstrated the effectiveness of P2X3 antagonists in the treatment of chronic cough. Basic studies have shown that non-selective P2X3 antagonists have obvious adverse effects of taste disturbance due to antagonizing P2X2/3 heterotrimers, and patients have poor compliance.

As a new generation of highly selective P2X3 antagonist, QR052107B can solve the adverse reactions of dysgeusia while maintaining the therapeutic efficacy, and has better safety. In addition, non-clinical studies have shown that QR052107B has a clear pharmacodynamic effect in animal pharmacodynamic models such as pain and itching. This clinical approval means that QR052107B has entered the research stage of multi-indication development.

Euho Pharma’s YH003 was granted an implied clinical license from CDE for the treatment of mucosal melanoma

On March 31, 2022, data from CDE’s official website showed that Euho Pharma’s CD40 monoclonal antibody YH003 was approved by CDE for clinical use. The indication is the treatment of unresectable/metastatic mucosal melanoma.

YH003 is a new humanized antibody that targets CD40, a member of the tumor necrosis factor receptor superfamily (TNFRSF) on the surface of immune cells, developed by Euho Pharma. By specifically activating the CD40 receptor signaling channel, it promotes the activation of innate immune cells such as dendritic antigen-presenting cells (DC), and positively regulates the effector activity of anti-tumor T cells. Studies to date have shown that CD40 activation is a key regulatory point in tumor immunotherapy, which can effectively convert cold tumors lacking immune cell infiltration into hot tumors that respond well to tumor immunotherapy.

In the preclinical antibody screening stage, Euho Pharma made full use of the tumor model in CD40 humanized mice independently developed by Biocytos, and quickly screened in mice to completely inhibit tumor growth without side effects such as hepatotoxicity. cloned antibodies. Whether used alone or in combination with anti-PD-1 monoclonal antibodies, YH003 has demonstrated strong anti-tumor effects on a variety of tumor models in mice. Pharmacodynamic studies in mice showed that YH003 significantly increased the proportion of anti-tumor T cells in tumor-infiltrating cells. Importantly, YH003 showed good safety even at very high doses, both in mice and monkeys.

CD40 (cluster of differentiation 40), expressed in APCs such as dendritic cells (DC), B cells, monocytes, as well as many non-immune cells and a wide range of tumors. The interaction of APC with its trimeric ligand CD154 on activated T helper cells results in the activation of APC, which mediates multiple functions including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. was found to be essential in various immune and inflammatory responses. Agonistic CD40 antibodies have been shown to activate APCs, promote antitumor T-cell responses, and culture cytotoxic myeloid cells, potentially controlling tumor growth in the absence of T-cell immunity. Agonistic CD40 antibodies have also been shown to activate tumor-killing macrophages and indirectly activate NK cells. Binding of CD40L to CD40 on endothelial cells stimulates the production of cytokines and chemokines and may promote tumor infiltration of immune cells such as T cells.

clinical progress

CStone Pharmaceuticals completes the first patient enrollment in Phase I clinical trials in the United States for the treatment of advanced B-cell lymphoma and solid tumors

On March 31, 2022, CStone Pharmaceuticals announced that CS5001 has completed the first patient enrollment in the Phase I clinical trial in the United States. This international multicenter Phase I clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of CS5001 in advanced B-cell lymphoma and solid tumors.

CS5001 is a potential global “Best-in-class” ADC drug targeting ROR1. ROR1 is a typical tumor embryonic protein with low or no expression in adult tissues, but high expression in various tumors, including various leukemias, non-Hodgkin lymphomas, breast, lung and ovarian cancers . Preclinical data show that CS5001 exhibits strong selective cytotoxicity in multiple ROR1-expressing tumor cell lines and significant in vivo antitumor activity in both hematological and solid tumor xenograft mouse models.

As one of the fastest ROR1 ADCs in the world, CS5001 has been approved to start an international multi-center Phase I clinical trial (NCT05279300) in the United States and Australia, and its clinical trial application in China was also approved by CDE on March 3, 2022 Accepted. According to the statistics of Yaodu, CS5001 of CStone is the first ADC drug targeting ROR1 by a domestic company, and Zilvertamab vedotin developed by Merck and Velosbio is the one with the fastest progress.

On January 13, 2022, Merck R&D (China) Co., Ltd. obtained an implied clinical license from CDE for the treatment of diffuse large B-cell lymphoma (CXSL2101418).

CS5001 is a license in drug introduced by CStone from South Korea. On October 29, 2020, CStone announced that it has entered into a licensing agreement with LegoChem Biosciences, Inc. (LCB) for the development and commercialization of LCB71 (CS5001). Under the terms of the agreement, CStone will receive an exclusive license to lead the development and commercialization of LCB71 (CS5001) in other parts of the world outside of Korea; LCB will receive an upfront payment of US$10 million and up to US$353.5 million Milestone payments and additional tiered royalties.

Pharmaceutical deals

Chengdu Sunna and Aoda Bio have reached an agreement on the transfer of anti-coronavirus polypeptide drugs, with an estimated total investment of 175 million yuan

On March 31, 2022, Chengdu shengnuo Biotechnology Co., Ltd. announced that its wholly-owned subsidiary Chengdu shengnuo Biopharmaceutical Co., Ltd. intends to cooperate with Chengdu Aoda Biotechnology Co., Ltd. The joint research and development of the anti-coronavirus polypeptide drug project (AOD53724) with independent intellectual property rights and the global exclusive right to use the patent of this project enjoyed by Aoda Bio have reached a cooperation.

According to the terms of the agreement, Aoda Bio will transfer the clinical approval documents of its projects in China (so far, no clinical approval documents have been obtained) and all rights related to the patent rights to shengnuopharm. The technology transfer fee is RMB 65,000,000 (tax included), which will be paid in installments by shengnuo Pharma according to the progress of the target project agreed in the “Transfer Contract”.

There are currently different research and development stages of new crown prevention and treatment drugs in the world, and a number of new crown vaccines have been launched in China; after inquiries, as of the end of 2021, 4 domestic new crown vaccine products have been conditionally approved for marketing, 3 have been approved for emergency use, and another has been approved for emergency use. A number of drugs are in the clinical trial stage; at the same time, a number of antibody and small molecule drugs are also in different development stages. AOD53724 is in the preclinical animal efficacy safety evaluation test stage, and it is expected to apply for clinical approval in China by the end of 2022.

In order to ensure the smooth progress of the AOD53724 project, the company needs to pay the clinical trial fees for each phase according to the progress of the project. It is estimated that the completion of the AOD53724 project will take 2 to 3 years, and the total investment is expected to be about RMB 175 million before the product is commercialized.