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QLETLI®

QLETLI®, the first approved biosesimilar to Humira in China, is currently approved for treatment of ankylosing spondylitis, rheumatoid arthritis, psoriasis, Crohn’s disease, and uveitis. QLETLI® binds specifically to soluble and membrane bound TNF-α and blocks its interaction with the p55 and p75 cell surface TNF receptors, effectively neutralizing TNF-α bioactivity. TNF-α is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF-α play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of certain diseases, such as ankylosing spondylitis, rheumatoid arthritis, psoriasis, and polyarticular juvenile idiopathic arthritis.

TOFIDENCE

BAT1806 is a recombinant humanized monoclonal antibody targeting interleukin-6 receptor (IL-6R), which specifically binds to soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R) and inhibits signaling mediated by sIL-6R or mIL-6R. BAT1806/TOFIDENCE is the first approved biosesimilar to Actemra® in China and US. FDA approves BAT1806 (TOFIDENCE™) (tocilizumab-bavi) in September, 2023. In the US, TOFIDENCE intravenous formulation is approved for the treatment of moderately to severely active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis. In China, BAT1806 is approved for the treatment of rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis (sJIA), and cytokine release syndrome (CRS). 

BAT2606

Mepolizumab is an interleukin-5 (IL-5) antagonist monoclonal antibody that is administered subcutaneously with a syringe or autoinjector.  Mepolizumab is currently indicated for the following conditions: 1) as an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype, 2) as an add-on maintenance treatment of adult patients 18 years and older with chronic rhinosinusitis with nasal, 3) the treatment of adult patients with eosinophilic granulomatosis with polyangiitis, 4) the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome for ≥6 months without an identifiable non-hematologic secondary cause. 

* BAT6026

BAT6026, a novel mAb drug candidate with afucosylated modification that targets OX40 for oncology treatment. While OX40 is a co-stimulatory immune checkpoint which is contrary to PD-1 or CTLA4 that are inhibitory checkpoints, OX40 is also high expressed in Regulatory T Cells (Tregs). BAT6026,as an anti-OX40 agonist antibody, has three potential modes of mechanism in cancer therapy: 1) stimulating CD4+ and CD8+T cells directly; 2) inhibiting Tregs by cellular signal; and 3) depleting Tregs highly expressing OX40 by engaging Fc gamma receptors expressed by tumor-associated effector cells, such as natural killer cells.

BAT4406F

BAT4406 is an investigational ADCC-enhanced anti-CD20 mAb candidate in clinical development for the treatment of autoimmune diseases. BAT4406F is currently being evalsuated in NMOSD, an orphan indication with an estimated prevalsence of 0.5 to 10 per 100,000. BAT4406 is a type I glyco-engineered mAb that binds specifically to CD20 on B-cells, kills the B-cells by CDC, and enhances ADCC effect. B cells have been implicated in the pathogenesis of a number of autoimmune diseases, including the CNS disorders, multiple sclerosis (MS) and NMOSD. Depletion of B-cells could provide meaningful relief for these autoimmune diseases. NMOSD is an autoimmune inflammatory disorder of the central nervous system (CNS) with preferential localization to the optic nerve, spinal cord and brain stem. Patients typically experience bouts of vision loss or blindness, attacks of myelitis with often severe motor impairment including loss of ambulation, sensory disturbances, bowel/bladder dysfunction, and brainstem attacks with characteristic episodes of intractable nausea, vomiting and hiccups.

BAT2506

BAT2506 is biosesimilar candidate to Simponi (golimumab), which is a once-a-month self-injectable TNF-α inhibitor. Simponi is approved by the FDA and EMA for treatment of adult patients with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and ulcerative colitis. As a Simponi (golimumab) biosesimilar, BAT2506 binds to both the soluble and transmembrane bioactive forms of human TNF-α. This interaction prevents the binding of TNF-α to its receptors, thereby inhibiting the biological activity of TNF-α. Elevated TNF-α levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. TNF-α is an important mediator of the articular inflammation that is characteristic of these diseases.

BAT2306

BAT2306 is a biosesimilar drug candidate to Cosentyx (secukinumab). Secukinumab is approved for the treatment of plaque psoriasis, psoriatic arthritis, ankylosing spondylitis (AS, radiographic axial spondyloarthritis) and non-radiographic axial spondyloarthritis (nr-axSpA). In China, Secukinumab is approved for the treatment of plaque psoriasis and ankylosing spondylitis. Secukinumab selectively targets Interleukin 17A (IL-17A). IL-17A, produced mainly by a subset of T helper cells, named Th17, as well as other T cells, neutrophils and mast cells, promotes the expression of other pro-inflammatory cytokines and effector proteins, leading to the activation of neutrophils and macrophages as well as epithelial cells and fibroblasts. This cascade is recognized to play an important role in the pathophysiology of many autoimmune diseases, including psoriasis. The mechanism of action offers greater specificity and selectivity in targeting the specific downstream cytokine.

BAT2206

BAT2206 is a biosesimilar drug candidate to Stelara (ustekinumab), a human monoclonal antibody initially approved by the FDA and primarily used to treat psoriasis, Crohn’s disease and ulcerative colitis. It inhibits the bioactivity of human IL-12 and IL-23 by preventing shared p40 from binding to the IL-12Rβ1 receptor protein expressed on the surface of immune cells. IL-12 and IL-23 are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn's disease and ulcerative colitis, among many other autoimmune diseases.

BAT2406

POBEVCY®

POBEVCY® is a monoclonal antibody (mAb) that is in development as a potential biosesimilar to Avastin®. POBEVCY® works by binding the vascular endothelial growth factor (VEGF) protein. In the U.S., Avastin® is indicated for the treatment of patients with metastatic colorectal cancer, non-squamous non-small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, persistent, recurrent, or metastatic cervical cancer. In China, Avastin has been approved for metastatic CRC and nsNSCLC. NMPA has approved POBEVCY® for the treatment of metastatic CRC and nsNSCLC, and BLA to FDA and MAA to EMA have been submitted.

* BAT4706

BAT4706 injection is a recombinant fully human Fc glycosylation modified anti-CTLA-4 monoclonal antibody for the treatment of solid tumors. BAT4706, as a second-generation CTLA-4 antibody, was shown to be more efficacious than the first generation of anti-CTLA-4 monoclonal antibody therapies, and has a great potential in the treatment of solid tumors, especially when administrated in combination therapy. CTLA-4 is a immune checkpoint expressed on regulatory T cells and activated CD4+ and CD8+ T cells. It competes with CD28 for binding to B7, thus functions through disruption of the B7-CD28 axis. BAT4706 binds to  CTLA-4 molecules to liberate B7 protein to restore its binding to CD28. At the same time, BAT4706 is designed to bind to CTLA-4 molecules leading to regulatory T cells depletion or functional blockade resulting in enhanced T cell activation and immunological responses to cancer.

BAT4306F

BAT4306F is a next-generation anti-CD20 mAb candidates with afucosylated modification resulting in higher level of ADCC activity compared to many of the marketed anti-CD20 antibody therapeutics, such as ofatumumab, ocrelizumab, rituximab . Increased ADCC activity of BAT4306F resulted in >100 fold more potent EC50 compared to that of rituximab, which in turn increases their B-cell depletion ability and translates into a potentially better efficacy, as compared to rituximab, the only anti-CD20 mAb approved in China for NHL. BAT4306F is a type 2 glyco-lengineered mAb that binds to CD20, leading to rearrangement of CD20 within the cell membrane and apoptosis. In addition, the constant region (Fc) of the mAb is completely defucosylated, resulting in a higher affinity for the Fc gamma receptors in polymorphonuclear (PMN) and natural killer (NK) cells. As a result, BAT4306F mechanisms of action are primarily ADCC and apoptosis.

BAT7104

BAT7104, an anti-PDL1/CD47 bispecific mAb, is designed to inhibit the PD-1/PD-L1 and CD47/SIRP-α pathways. In pre-clinical studies, the drug candidate was able to effectively block the binding of both pathways and mediate T cell activation and trigger phagocytosis of macrophage. BAT7104, as a next generation of anti-PDL1/CD47 bispecific mAb, does not bind to CD47 on red blood cells and preferentially binds to PD-L1 positive tumor cells over healthy cells, and thus decreases the possibility of toxic effect seen with some of the anti-CD47 antibodies in clinical trials, as CD47 is expressed in many normal tissues.

BAT1006

BAT1006 is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). BAT1006 inhibit tumor cell growth by blocking ligand dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4 ,which can further inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K), resulting in cell growth arrest and apoptosis, respectively. In addition, BAT1006 is a glycosylation engineered antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC).

BAT1308

BAT1308 is a humanized anti-PD-1 monoclonal antibody candidate for treatment of solid tumors. A phase I clinical trial for BAT1308 as monotherapy in solid tumors is currently ongoing. Clinical strategies for BAT1308 will be in combination therapies, such as with BAT1706, an anti-VEGF monoclonal antibody, for non-small cell lung cancer, among many solid tumors. PD-1 is a  immune checkpoint which is mainly expressed on activated T cells. In the tumor micro-environment, PD-L1 and PD-L2 on tumor cells bind to its receptor PD-1 in T cells, and inhibit T cell proliferation and activation, and thus suppress the anti-tumor activities of immune cellls. BAT1308, as a PD-1 inhibitor, binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, and restores the anti-tumor activities of T cells.

BAT8006

BAT8006, is an antibody drug conjugate (ADC) that targets folic acid receptor α (FRα). FRα is a folic acid-binding protein located on cell membranes that is overexpressed in a variety of solid tumors such as ovarian, lung, breast cancer, etc., but has a limited distribution and a lower level of expression in normal human tissues. Differences in expression levels make FRα an ideal target for ADC drug development.  BAT8006 was developed using Bio-Thera's anti-FRα antibody and Bio-Thera’s proprietary ADC linker-payload combination that includes a systemically stable and cleavable linker and a small molecule topoisomerase I inhibitor. A series of preclinical studies have shown that BAT8006 has good stability and safety and has high anti-tumor activity. The small molecule topoisomerase I inhibitor payload carried by BAT8006 has a strong cell membrane penetration ability, so when the target cancer cells are killed, the payload can be released and further kill nearby cancer cells, producing a bystander effect and effectively overcoming the heterogeneity of the tumor. BAT8006 has demonstrated high anti-tumor activity and good safety in both in vitro and in vivo pharmacological studies and is a potential "best-in-class" ADC that targets FRα.

BAT8010

BAT8010 is an antibody-drug conjugate (ADC) targeting HER2 designed for the treatment of solid tumors. BAT8010 was developed by using Bio-Thera’s proprietary ADC linker-payload that includes a cleavable but systemically stable linker, a small molecule topoisomerase I inhibitor and high DAR. The small molecule topoisomerase I inhibitor payload carried by BAT8010 has a strong cell membrane penetration ability, when the target cancer cells are killed, the payload has shown to be released and kill nearby cancer cells, producing a bystander effect, which has the potential to overcome the heterogeneity of the tumor. BAT8010 has demonstrated high anti-tumor activity, good stability, and safety in both in vitro and in vivo pharmacological studies. 

BAT8008

BAT8008 is an antibody-drug conjugate (ADC) targeting Trop2 designed for the treatment of solid tumors. Trop2 (Trophoblast cell-surface antigens 2), also known as TACSTD2, M1S1, GA733-1, EGP-1, is a member of tumor associated calcium signal transduction protein (TACSTD) family, which is related to the regulation of intracellular calcium concentration. BAT8008 was developed by using Bio-Thera’s proprietary ADC linker-payload that includes a cleavable but systemically stable linker, a small molecule topoisomerase I inhibitor and high DAR. The small molecule topoisomerase I inhibitor payload carried by BAT8008 has a strong cell membrane penetration ability.  Consequently, when targeted cancer cells are killed, the payload has shown to be released and kill nearby cancer cells, producing a bystander effect, which has the potential to overcome the heterogeneity of the tumor. BAT8008 has demonstrated high anti-tumor activity, good stability, and safety in both in vitro and in vivo pharmacological studies.

BAT8007

BAT8007 is an antibody-drug conjugate (ADC) targeting Nectin-4 designed for the treatment of solid tumors. Nectin-4 (Nectin cell adhesion molecule 4) belongs to the nectin subfamily of immunoglobulin-like adhesion molecules that participate in Ca(2+)-independent cell-cell adhesion.  Nectin-4 has high expression levels in a normal embryo and fetal tissues, while those expression levels decline in adulthood and has limited distribution in healthy tissues.

BAT7205

BAT7205 is an anti-PD-L1/IL-15 bi-functional fusion protein developed by Bio-Thera Solutions, Ltd. for the treatment of adult patients with locally advanced or metastatic solid tumors. IL-15 a multipotent cytokine with immunostimulatory properties that promotes the expansion and activation of memory CD8+T cells and NK cells, also the tumor-infiltrating CD8+T cells which are not responded to PD-1 inhibitor treatment. Thus, IL-15 has therapeutic potential to improve clinical efficacy of anti-PD-1/PD-L1 checkpoint inhibitors. BAT7205 is an anti-PD-L1 monoclonal antibody fused with IL-15/IL-15Rα sushi domain. It can block the PD-1/PD-L1 immunosuppressive pathway via binding to PD-L1 and activate the immune system through its IL-15 part, thus playing a synergistic role of relieving immunosuppression and boosting the immune activation to exhibit antitumor effect. Fusion of IL-15 to full anti-PD-L1 mAb would deliver IL-15 directly to the PD-L1+ tumor microenvironment to activate tumour-infiltrating CD8+T cells and NK cells, thus avoid potential systemic side effects of IL-15. It also enhances the half-life of IL-15 for a longer-lasting biological function.

BAT3306

BETAGRIN®

BAT2094 is peptide mimetic ß3 integrin (αIIbß3, αvß3) antagonist intended for the prevention of  platelet aggregation-induced thrombus (blood clot) for patients who undergo percutaneous coronary intervention (PCI) procedures. Platelet glycoprotein (GP) IIb/IIIa antagonists have been extensively applied in the treatment of ACS patients undergoing PCI, and have consistently presented the improved clinical outcomes. BAT2094 (Batifiban), a cyclic heptapeptide mimetics, is an intravenous antagonist of the GP IIb/IIIa integrin receptor, inhibiting platelet aggregation by blocking fibrinogen binding to the GP IIb/IIIa . BAT2094 can also bind to integrin αvß3 of endothelial and smooth muscle cells, thus potentially preventing integrin αvß3-induced adhesion and spreading of platelets and endothelial cells, and the resulted restenosis of blood vessels.

BAT5906

BAT5906 is a recombinant humanized full monoclonal antibody candidate targeting VEGF for the treatment for wet age-related macular degeneration (wAMD), diabetic eye diseases such as diabetic macular edema (DME), and other conditions. BAT5906 is currently under Phase II clinical trials for both wAMD and DME. VEGF has been shown to cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion, and is thought to contribute to pathophysiology of multiple eye conditions. The wAMD causes edema of the retina and fluid leakage due to the abnormal blood vessel growth, and if untreated, can eventually lead to blindness. The binding of BAT5906 to VEGF-A prevents its interaction with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, thus reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.