Icotinib hydrochloride (Conmana®) is a national Category 1.1 innovative drug that has been independently developed by Betta Pharmaceuticals for nearly a decade and Betta Pharmaceuticals owns proprietary intellectual property rights. Icotinib is the first domestically-developed small molecule targeted therapy for lung cancer by a Chinese company. It is a potent, highly selective and orally available small molecule EGFR-TKI that could be used as a single agent suitable for the treatment of EGFR gene with sensitive mutation first-line treatment for patients with NSCLC.

lung cancer

Vectibix is an all human anti epidermal growth factor receptor monoclonal antibody (IgG2) developed by Amgen, which is mainly used for targeted treatment of RAS wild-type patients with advanced colorectal cancer. Approved by the United States for the first time in September 2006, it has been listed in 77 countries around the world. At present, 6000 clinical trial subjects and 280000 post marketing patients have been treated with panitumumab. Betta has signed a joint venture with Amgen to introduce panitumumab to be listed in China, which is currently being promoted.

colorectal cance

MIL60 is a targeted antibody drug for human vascular endothelial growth factor (VEGF). It is a bevacizumab biosimilar, which can be used to treat non-small cell lung cancer, colorectal cancer and other solid tumor indications. MIL60 can inhibit tumor angiogenesis by inhibiting the binding of VEGF and VEGFR, so as to cut off tumor feeding and prevent tumor growth. A phase III clinical trial is evaluating the first-line treatment of MIL60 combined with carboplatin and paclitaxel in advanced, metastatic or recurrent NSCLC.

lung cancer, colorectal cancer

Vorolanib (CM082) is a novel next-generation of multi-target kinase inhibitor, which can inhibit tumor angiogenesis and growth, and can be used in the treatment of many kinds of cancer. Vorolanib has a significant anti-angiogenic effect on VEGFR, PDGFR, c-Kit, Flt-3, CSF1R and other multiple targets, and the special PK/PD of vorolanib can preserve activity and reduce toxicity. A phase II/III clinical trial (CONCEPT) is evaluating vorolanib in combination with everolimus in the treatment of patients with advanced renal cell carcinoma.

renal cell carcinoma

Ensartinib (X-396, ) is a novel, potent and highly selective next-generation inhibitor of anaplastic lymphoma kinase (ALK), which has a potency more than ten-times greater than crizotinib in enzymatic assays. Ensartinib targets ALK, inhibiting downstream malignant pathways that contribute to tumorigenesis and disease progression. Ensatinib has shown good efficacy in in vitro and in vivo studies, including those tumors that are already resistant to clozatinib, and has inhibitory effects on c-Met, TRK 1/ 2/ 3, ROS1, etc. A phase III head to head trial is evaluating ensartinib as the first-line treatment in patients with ALK-positive non-small cell lung cancer as compared with crizotinib.

lung cance

Balstilimab is a human monoclonal antibody targeting programmed cell death protein 1 (PD-1), and is an immune checkpoint inhibitor. Balstilimab potently antagonizes PD-1 binding to PD-L1 and PD-L2, relieves T cell suppression, and enhances T cell effector function, therefore activating the immune system to attack tumor. Balstilimab as a single agent and in combination with Zalifrelimab, an anti-CTLA-4 antibody, is planned for clinical investigation for the treatment of advanced cervical cancer as well as other advanced solid tumors. The IND applications for Balstilimab have been accepted by NMPA CDE and are currently in technical review.

Zalifrelimab is a human monoclonal antibody targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and is an immune checkpoint inhibitor. By blockade of CTLA-4 binding to its ligands, CD80 and CD86, Zalifrelimab antagonizes the negative regulation of T cells by CTLA-4, therefore enhancing tumor immune surveillance and anti-tumor response. Zalifrelimab is planned for clinical investigation in combination with Balstilimab, an anti-PD-1 antibody, for the treatment of advanced cervical cancer as well as other advanced solid tumors. The IND applications for Zalifrelimab have been accepted by NMPA CDE and are currently in technical review.

Vorolanib (CM082) is a novel next-generation of multi-target kinase inhibitor, which can inhibit tumor angiogenesis and growth, and be used in the treatment of many kinds of cancer. Toripalimab (JS001) is a new type of recombinant humanized anti-PD-1 monoclonal antibody, which was approved by National Medical Products Administration in China on December 17, 2018, and used for locally progress or metastatic melanoma after previous standard treatment failure. A phase II trial is evaluating the vorolanib in combination with the toripalimab for the treatment of patients with locally progress or metastatic melanoma.

melanoma

Vorolanib (CM082) is a novel next-generation of multi-target kinase inhibitor, which can inhibit tumor angiogenesis and growth, and can be used in the treatment of many kinds of cancer. Vorolanib has a significant anti-angiogenic effect on VEGFR, PDGFR, c-Kit, Flt-3, CSF1R and other multiple targets, and the special PK/PD of vorolanib can preserve activity and reduce toxicity. A phase II clinical trial is evaluating vorolanib in the treatment of patients with wet age-related macular degeneration, and patients showed well tolerance and significant visual improvement.

wet age-related macular degeneration

BPI-3016 is a novel diabetes drug independently developed by Betta. It is the first super long-term glucagon like peptide-1 (GLP-1) analogue obtained by structural modification of the main chain of natural GLP-1 in China. BPI-3016 retains the multiple effects of natural GLP-1, and overcomes its easily degradable characteristics. It not only has good biological activity, but also can reduce body weight and improve the function of β cells. Meanwhile, BPI-3016 has good subcutaneous absorption and long half-life, supporting the design expectation of weekly administration with good safety. It has unique advantages in the treatment of type II diabetes as well as prevention and treatment of cardiovascular risk. At present, clinical research is being promoted.

Diabetes mellitus II

BPI-16350 is a novel antitumor drug independently developed by Betta. It is a cyclin dependent kinase CDK4 and CDK6 inhibitor with new structure. CDK4/6 are the key factors to regulate cell cycle, which can trigger cell cycle transition from G1 phase to S phase. BPI-16350 can specifically combine with CDK4/6 to inhibit the kinase activity, inhibit the proliferation, metastasis and other related signal transduction of cancer cells, block the cell cycle in G1 phase, thus inhibiting the proliferation of tumor cells. The clinical trial of BPI-16350 in breast cancer has been approved and is now ongoing.

breast cancer

BPI-23314 is a novel molecular compound independently developed by Betta with completely independent intellectual property rights. It is a potent and highly selective bromodomain and extra-terminal domain (BET) oral small molecule inhibitor. BPI-23314 can specifically inhibit the function of BET family proteins, regulate the transcription and expression of cancer-related genes, and then affect cell growth, proliferation, apoptosis and other physiological processes, thus inhibiting tumor growth. The clinical trial of BPI-23314 has been approved and is now ongoing.

solid tumors, hematological malignancies

BPI-17509 is a novel, potent and highly selective small molecule oral inhibitor of fibroblast growth factor receptor (FGFR1/2/3) independently developed by Betta. It is intended to be used in various tumor therapies with FGFR gene. FGFR plays an important role in tumor proliferation, angiogenesis, migration and survival. BPI-17509 can specifically inhibit the activity of FGFR1/2/3, block the related signal transduction pathway, and then affect several physiological processes such as cell proliferation, apoptosis, migration, neovascularization in vivo, thus inhibiting tumor growth. The clinical trial application of BPI-17509 has been approved and is now ongoing.

solid tumors

BPI-43487 is a new molecule internally developed by Betta Pharmaceuticals and we own proprietary intellectual property rights. It is a potent and selective inhibitor of FGFR4 with a covalent irreversible binding mode, designed for the treatment of solid tumors including a subset of hepatocellular carcinoma and cholangiocarcinoma that are driven by alterations in the FGF19/FGFR4 signaling pathway. In preclinical studies, BPI-43487 showed strong binding affinity toward FGFR4 and high selectivity against other FGFR kinases. It exhibited desirable metabolic properties in vivo, achieving a good balance between pharmacodynamics and pharmacokinetics, and a good safety window. The IND application for BPI-43487 has been approved and is progressing smoothly.

solid tumors, hematological malignancies

BPI-361175 is a novel, oral, highly potent and selective 4th generation EGFR inhibitor developed by Betta Pharmaceutical Co., Ltd. The new chemical entity targets EGFR C797S mutation and other EGFR related mutations that are resistant to 3rd generation EGFR TKI in non-small cell lung cancer (NSCLC) and other solid tumors. It shows excellent inhibitory effect and selectivity in vitro assay and exhibits significant anti-tumor activity in a variety of xenograft models harboring EGFR C797S or other related mutations. The IND application of BPI-361175 has been approved by NMPA, and Phase 1 clinical trial is being initiated.

BPI-21668 is a novel, potent and selective small molecule inhibitor of Phosphatidylinositol 3-kinase α (PI3Kα) developed by Betta Pharma. It is intended to be used for the treatment of advanced solid tumor with PIK3CA mutations. BPI-21668 shows consistent biological activities in vitro and in vivo. It can potently and selectively inhibit proliferation of PIK3CA-mutant cells. Used as a single agent or in combination, BPI-21668 shows good anti-tumor effect in multiple solid tumor models. BPI-21668 also exhibits excellent physicochemical and pharmacokinetic properties. The IND application of BPI-21668 has been approved by NMPA, and Phase 1 clinical trial is starting.

MCLA-129 is a bispecific antibody targeting both EGFR and c-Met. MCLA-129 can simultaneously block the signal transductions of EGFR and c-MET, therefore inhibiting tumor growth and survival. Through enhanced ADCC and ADCP activities, MCLA-129’s tumor cell killing potential is further increased. MCLA-129 is planned for clinical investigation for the treatment of advanced solid tumors with EGFR or MET abnormalities. The clinical trial for MCLA-129 has been approved and is currently under development.

BPI-421286 is an innovative molecule which we own complete proprietary intellectual property rights. It’s a new type of potent and selective orally available small-molecule inhibitor of KRASG12C with a covalent irreversible binding mode, intended to be used to treat patients who carry KRASG12C specific mutated oncogene in unresectable, locally advanced or metastatic solid tumors. Preclinical data has shown that BPI-421286 has the same biological activity in vivo and in vitro, which can effectively inhibit the proliferation of tumor cells carrying KRASG12C mutations, and has shown good anti-tumor effects on a variety of transplanted tumor models carrying KRASG12C mutations. At present, the drug clinical trial application for BPI-421286 capsules has been approved and is progressing smoothly.