About CASI Pharmaceuticals

CASI Pharmaceuticals, Inc. (CASI), a biopharmaceutical company, focuses on developing and commercializing innovative therapeutics and pharmaceutical products in China, the United States, and throughout the world. The company focuses on acquiring, developing and commercializing products that augment its hematology oncology therapeutic focus, as well as other areas of unmet medical need. The majority of the company's operations and activities are located in China and are conducted primarily through two subsidiaries: CASI Pharmaceuticals (China) Co., Ltd. (CASI China), which is wholly owned and is located in Beijing, China; and CASI Pharmaceuticals (Wuxi) Co., Ltd. (CASI Wuxi), which is located in Wuxi, China. Core Product and Candidates In Hematology/Oncology EVOMELA (Melphalan for Injection) - Launched In China: EVOMELA (Melphalan for Injection) is an intravenous formulation of melphalan commercialized by Acrotech (formally by Spectrum) in the multiple myeloma treatment setting in the United States, of which the company has exclusive greater China rights. The EVOMELA formulation avoids the use of propylene glycol, which is used as a co-solvent in other formulations of injectable melphalan. The use of Captisol in the EVOMELA formulation improves the melphalan stability when reconstituted, allowing for longer preparation and infusion times. In August 2019, the company launched EVOMELA in China as its first commercial product. The NMPA required post-marketing study has completed and the clinical study report is being finalized for regulatory submission. CNCT19 (CD19 CAR-T): The company holds worldwide license and commercialization rights to CNCT19 from Juventas Biotechnology (Tianjin) Co., Ltd. (Juventas), a China-based domestic company engaged in cell therapy. Juventas continues to be responsible for the clinical development and regulatory submission and maintenance of CNCT19 regulatory applications and the company is responsible for the launch and commercial activities of CNCT19 under the direction of a joint steering committee. CNCT19 is an autologous CD19 CAR-T investigative product (CNCT19) being developed by the company's partner Juventas for which it has exclusive worldwide co-commercial and profit-sharing rights. CNCT19 targets CD19, a B-cell surface protein widely expressed during all phases of B-cell development and a validated target for B-cell driven hematological malignancies. CD19 targeted CAR constructs from several different institutions have demonstrated consistently high antitumor efficacy in children and adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and B-cell non-Hodgkin lymphoma (B-NHL). CNCT19 is being developed as a potential treatment for patients with hematological malignancies which express CD19, including, B-ALL and B-cell non-Hodgkin lymphoma (B-NHL). Juventas has completed the CNCT19 Phase 1 studies in patients with B-ALL and B-NHL, and has completed the Phase 2 B-ALL pivotal study in China, while the B-NHL registration study is still ongoing in China. In December 2022, PRC National Medical Products Administration (NMPA) has accepted the NDA from Juventas for CNCT19 for the treatment of adult patients with relapsed/refractory B-ALL. BI-1206 (anti-FcyRIIB antibody): The company has an exclusive licensing agreement with BioInvent International AB (BioInvent) for the development and commercialization of novel anti-FcyRIIB antibody, BI-1206, in mainland China, Taiwan, Hong Kong, and Macau. BioInvent is a biotechnology company focused on the discovery and development of first-in-class immune-modulatory antibodies for cancer immunotherapy. BI-1206 is being investigated by BioInvent in a Phase 1/2 trial, in combination with anti-PD1 therapy Keytruda (pembrolizumab), in patients with solid tumors, and in a Phase 1/2a trial in combination with MabThera (rituximab) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Clinical Trial Application (CTA) was approved by NMPA in December 2021 and ethics committee approvals have been received in January of 2022. The company obtained approval from Human Genetic Resources Administration of China (HGRAC) in April 2022. The company is planning a Phase 1 study of BI-1206 in combination with rituximab with a single agent BI-1206 run in phase in patients with NHL (mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma) to assess PK, safety and tolerability, select the Recommended Phase 2 Dose and assess early signs of clinical efficacy as part of its development program for BI-1206 in China. The study received regulatory approval from the China Center for Drug Evaluation (CDE) in the second quarter (year ended December 2022) of 2022, and the first patient was enrolled and dosed in the third quarter of 2022. CB-5339 (VCP/p97inhibitor): CB-5339 is a novel VCP/p97 inhibitor focused on valosin-containing protein (VCP)/p97 as a novel target in protein homeostasis, DNA damage response and other cellular stress pathways for therapeutic use in the treatment of patients with various malignancies. The company has an exclusive license with Cleave Therapeutics, Inc. (Cleave) for the development and commercialization of CB-5339 in mainland China, Hong Kong, Macau, and Taiwan. CB-5339, an oral second-generation, small molecule VCP/p97 inhibitor, is being evaluated in a Phase 1 clinical trial in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The CDE has responded to CB-5339 CTA application for the multiple myeloma indication submitted in March 2022 and the company has completed and submitted its response to the CDE. CID 103 (anti-CD38 monoclonal antibody): CID-103 is a full human IgG1 anti-CD38 monoclonal antibody recognizing a unique epitope that has demonstrated an encouraging preclinical efficacy and safety profile compared to other anti-CD38 monoclonal antibodies, and which the company has exclusive global rights. CID-103 is being developed for the treatment of patients with multiple myeloma. The Phase 1 dose escalation and expansion study of CID-103, in patients with previously treated, relapsed or refractory multiple myeloma is closed to further accrual in France and the U.K. Thiotepa: The company has an exclusive China license and distribution rights to a novel formulation of thiotepa, a chemotherapeutic agent, which has multiple indications, including as a conditioning treatment for use prior to certain allogeneic haemopoietic stem cell transplants. Thiotepa has a long history of established use in the hematology/oncology setting. The company is applying for generic registration and, subject to regulatory and marketing approvals, it intends to advance and commercialize this product in China. License and Distribution Agreements Acrotech License Arrangements: The company has product rights and perpetual exclusive licenses from Acrotech Biopharma L.L.C. (Acrotech) to develop and commercialize its commercial product EVOMELA in the greater China region (which includes Mainland China, Taiwan, Hong Kong, and Macau). The exclusive licenses held by the company were originally licensed from Spectrum Pharmaceuticals, Inc. (Spectrum), and Spectrum completed the sale of its portfolio of FDA-approved hematology/oncology products, including EVOMELA to Acrotech. The company received NMPA's approval for importation, marketing and sales in China and in 2019 it launched commercial sales of EVOMELA in China. The NMPA required post-marketing study has completed and the clinical study report is being finalized for regulatory submission. The company has established relationships, coupled with supply agreements, to secure the necessary resources to supply the EVOMELA commercial drug product, as well as any clinical trials materials required for its clinical development program. As an import drug product into China, the company expects that the future supply of EVOMELA will continue to be met by its partner Acrotech and its contract manufacturers. China Resources Pharmaceutical Commercial Group International Trading Co., Ltd.: The company has a three-year exclusive distribution agreement with China Resources Pharmaceutical Commercial Group International Trading Co., Ltd. (CRPCGIT), to appoint CRPCGIT on an exclusive basis as its distributor to distribute EVOMELA in the territory of the People's Republic of China (excluding Hong Kong, Taiwan and Macau), subject to certain terms and conditions. The company's internal marketing and sales team are responsible for commercial activities, including, for example, direct interaction with Key Opinion Leaders (KOL), physicians, hospital centers and the generation of sales. The agreement was renewed in March 2022 for another two years. Precision Autoimmune Therapeutics Co., Ltd.: In May 2022, the company entered into a Sublicense Agreement (the Sublicense Agreement) with PAT, a company established under the laws of China, pursuant to which it granted PAT an exclusive (subject to the commercialization and co-marketing rights), perpetual, worldwide license, with the right to freely grant further sublicenses subject to terms and conditions in the Sublicense Agreement, for the investigational anti-CD38 monoclonal antibody TSK011010 licensed and controlled by it from Black Belt Therapeutics Limited, in the treatment, prevention and diagnosis of autoimmune diseases, conditions and disorders in humans. Juventas License Arrangements: The company has a license agreement for exclusive worldwide license to commercialize an autologous anti-CD19 T-cell therapy product (CNCT19) from Juventas (the Exclusive License Agreement). Juventas is a China-based company engaged in cell therapy. BioInvent International AB: The company has an exclusive licensing agreement with BioInvent for the development and commercialization of novel anti-FcyRIIB antibody, BI-1206, in mainland China, Taiwan, Hong Kong and Macau. BioInvent is a biotechnology company focused on the discovery and development of first-in-class immune-modulatory antibodies for cancer immunotherapy. BI-1206 is being investigated in a Phase 1/2 trial, in combination with anti-PD1 therapy Keytruda (pembrolizumab), in patients with solid tumors, and in a Phase 1/2a trial in combination with MabThera (rituximab) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). The company is planning a Phase 1 study of BI-1206 in combination with rituximab with a single agent BI-1206 run in phase in patients with NHL (mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma) to assess PK, safety and tolerability, select the Recommended Phase 2 Dose and assess early signs of clinical efficacy as part of its development program for BI-1206 in China. The study received regulatory approval from the CDE in the second quarter of 2022, and the first patient was enrolled and dosed in the third quarter of 2022. Under the terms of the agreement, BioInvent and CASI will develop BI-1206 in both hematological malignancies and solid tumors, with CASI responsible for commercialization in China and associated markets. As an import drug product into China, the company expects that future supply of BI-1206 will be met by its partner BioInvent and its contract manufacturers. For local development in China, the company expects that its materials and commercial inventory will be supplied by one or more contract manufacturers. Black Belt Therapeutics Limited: The company has a license agreement with a newly established, privately held UK Company Black Belt Therapeutics Limited (Black Belt) for exclusive worldwide rights to CID-103, an investigational anti-CD38 monoclonal antibody (Mab). Cleave Therapeutics, Inc.: The company has an exclusive license with Cleave Therapeutics, Inc. (Cleave) for the development and commercialization of CB-5339, an oral novel VCP/p97 inhibitor, in both hematological malignancies and solid tumors, in Mainland China, Hong Kong, Macau, and Taiwan. Cleave is a clinical-stage biopharmaceutical company focused on valosin-containing protein (VCP)/p97 as a novel target in protein homeostasis, DNA damage response and other cellular stress pathways for therapeutic use in the treatment of patients with cancer. CB-5339 is being evaluated by Cleave in a Phase 1 clinical trial in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Under the terms of the agreement, the company is responsible for development and commercialization in China and associated markets. As an import drug product into China, the company expects that future supply of CB-5339 will be met by its partner Cleave and its contract manufacturers. For local development in China, the company expects that its clinical materials and commercial inventory will be supplied by one or more contract manufacturers. Riemser Pharma GmbH: The company has an Exclusive License and Distribution Agreement with Riemser Pharma GmbH (Riemser), pursuant to which it obtained exclusive distribution rights for Thiotepa in China. Under the agreement, Riemser will be responsible for manufacturing and supplying the company with clinical trials materials and commercial drug product, and costs of clinical trials (if any) for the registration, product launch and commercialization of Thiotepa in China. In November 2022, the company entered into an Amendment with Esteve Healthcare, S.L. (ESTEVE), pursuant to which it and Esteve will equally share the costs of clinical trials (if any) for the registration of Thiotepa in China. After the product is launched, the company will be subject to annual minimum purchase as prescribed in the agreement. Pharmathen Global BV: The company has an exclusive distribution agreement with Pharmathen Global BV (Pharmathen) for the development and distribution of Octreotide LAI microsphere in China. Octreotide LAI formulations, which are approved in various European countries, are considered a standard of care for the treatment of acromegaly and the control of symptoms associated with certain neuroendocrine tumors. In February 2023, the company entered into a Termination Agreement and Release with Pharmathen, pursuant to which both parties agreed to terminate the exclusive distribution license agreement in 2019 with respect to product Octreotide LAI, it returned all confidential information provided by Pharmathen and cancelled all regulatory approvals or other registrations it had obtained as an authorized distributor. Strategy The company's business development strategy focuses on acquiring additional targeted drugs and immuno-oncology therapeutics through licensing that will expand its hematology/oncology franchise. In many cases its business development strategy includes direct equity investments in the licensor company. Intellectual Property With regards to the company's commercial drug EVOMELA licensed for greater China rights from its partner, it has acquired exclusive licenses to intellectual property to enable it to develop and continue to commercialize EVOMELA in China. With regards to CNCT19, the company has acquired an exclusive license to intellectual property from its partner Juventas to enable it to co-commercialize CNCT19 in China and well as the rest of the world. Juventas is responsible for prosecuting and maintaining the licensed intellectual property. With regards to BI-1206, the company has acquired an exclusive license to intellectual property and the know-how from its partner BioInvent to enable it to develop and commercialize BI-1206 in its greater China commercial markets. BioInvent is responsible for prosecuting and maintaining the licensed BioInvent intellectual property. With regards to CB-5339, the company has acquired an exclusive license to intellectual property and the know-how from its partner Cleave to enable it to develop and commercialize CB-5339 in its greater China commercial markets. Cleave is responsible for prosecuting and maintaining the licensed Cleave intellectual property. With regards to the company's in-licensed anti-CD38 antibody candidate CID-103, it has acquired an exclusive worldwide license to patents around CID-103 and other anti-CD38 antibodies, covering multiple pending applications worldwide, directed to the antibodies themselves and treatment methods using the antibodies. The company has since filed additional applications, with current pending applications, including the U.S., Australia, Canada, China, Europe, India, Japan, Korea, New Zealand, Singapore and Hong Kong. The company intends to further expand its patent portfolio and in the submission stage of additional applications. The patent term for any patents granted from the earliest of these pending applications will expire in June 2038, assuming all annuities are paid and not considering any term extensions for regulatory approval that might be available. With regards to the Thiotepa drug candidate, the company has acquired exclusive licenses to intellectual property and/or the know-how to enable it to develop and commercialize this drug candidate in the China market. The company holds certain intellectual property in connection with a proprietary aurora kinase inhibitor that it no longer devotes resources to. The company's intellectual property for this asset remains available for business development partnering. The company owns a number of registered trademarks and pending trademark applications for CASI, including its corporate logo and product name in the United States, China and other jurisdictions, and it is seeking further trademark protection for CASI, including its corporate logo, product name, and other marks in jurisdictions where available and appropriate. Research and Development For the year ended December 31, 2022, the company's research and development expenses were US$16.0 million. Regulation The company or its collaborators must conduct adequate and well-controlled clinical trials, in accordance with applicable Investigational New Drug Application (IND) regulations, Good Clinical Practices (GCPs), and other clinical-trial related regulations, to establish the safety and efficacy of the candidate for each proposed indication. The company is subject to regulation and oversight by different levels of the Medical Products Administration and Administration of Market Regulation in China. The company is also subject to other People's Republic of China (PRC) laws and regulations that are applicable to pharmaceutical manufacturers and distributors in general, such as Drug Registration Regulation (DRR), which was updated on January 22, 2020, and became effective on July 1, 2020. History CASI Pharmaceuticals, Inc. was founded in 1991. The company was incorporated under the laws of the Cayman Islands in 1991.