Bio-Thera Solutions, Ltd.,

Therapeutic area
Product
Target
Pre-clinical
Phase I
Phase II
Phase III
NDA
Autoimmune Disease
    QLETLI®TNF-α

    QLETLI®

    QLETLI®, the first approved biosimilar 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.

    BAT1806IL-6R

    BAT1806

    BAT1806 is a tocilizumab biosimilar candidate of Actemra/RoActemra, currently undergoing a global phase III clinical trial. We expect to complete the global phase III trial and file the NDA in 2021. Actemra/RoActemra(tocilizumab) is prescribed to patients with RA, pJIA , sJIA, giant cell arteritis and CAR-T cell-induced cytokine release syndrome in the US and EU countries. In China, Actemra was launched in March 2013 and approved for treatment of RA and sJIA.

    Tocilizumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling, such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation.

    BAT2506TNF-α

    BAT2506

    BAT2506 is biosimilar 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. BAT2506 is planned to enter a global phase III clinical trial in Q12021. As a Simponi (golimumab) biosimilar, 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.

    BAT2206IL-12 and IL-23

    BAT2206

    BAT2206 is a biosimilar 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.

    BAT4406FCD20

    BAT4406F

    BAT4406 is an investigational ADCC-enhanced anti-CD20 mAb candidate in clinical development for the treatment of autoimmune diseases. BAT4406F is currently being evaluated in NMOSD, an orphan indication with an estimated prevalence 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.

    BAT2306IL-17A

    BAT2306

    BAT2306 is a biosimilar 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.

Oncology
    BAT1706VEGF

    BAT1706

    BAT1706 is a monoclonal antibody (mAb) that is in development as a potential biosimilar to Avastin®. BAT1706 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. BLA has been submitted to NMPA, and BLA to FDA and MAA to EMA are expected to be submitted by Q42020. 

    BAT8001HER2

    BAT8001

    BAT8001 is a HER2-targeted antibody-drug conjugate. The anti-HER2 IgG1 antibody is covalently linked to a proprietary cytotoxin drug-linker Batansine (a 3AA-MDC compound) by a thioether bond. BAT8001 is in phase III as the second-line treatment for HER2-positive breast cancer, and is entering a phase II clinical trial for HER2-positive urothelial cancer. BAT8001 can selectively bind to HER2 receptor on the surface of tumor cells, and then internalized via the HER2 receptor, thus bring the cytotoxin selectively into tumor cells while sparing normal cells. The ADC inside lysosome is degraded by hydrolase to release cytotoxic metabolites including Batansine inside the cell. Batansine binds to tubulin thereby interfering with the self-assembly of microtubules, destroying the intracellular microtubule network, and causes tumor cell cycle arrest and death eventually. HER2 is overexpressed in many types of cancer, especially breast cancer, gastric cancer and urothelial cancer.

    BAT1306PD-1

    BAT1306

    BAT1306 is a recombinant humanized anti-PD-1 mAb candidate under development for treatment of solid tumors. We are currently conducting clinical trial of BAT1306 in gastric cancers. 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. BAT1306, 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.

    BAT4306FCD20

    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.

    BAT8003Trop2

    BAT8003

    BAT8003 is an anti-Trop2 ADC. It is intended with uncleavable drug-linker combination Batansine for the treatment of Trop2 positive advanced solid tumor. Upon binding to Trop2 receptor, BAT8003 undergoes receptor-mediated internalization and subsequent lysozymal degradation, resulting in intracellular release of cytotoxic catabolite Cys-Batansine. Binding of Cys-Batansine to tubulin prevent s microtubule formation in the cell, thus causes cell cycle arrest and apoptotic cell death. Besides the ADC technology, BAT8003 is also glycoengineered by afucosylation of the Fc region to enhance its antibody-dependent cell-mediated cytotoxicity (ADCC) effect. Trop2 is a transmembrane glycoprotein that has high expression in various epithelial cancers. The specific high expression and its correlation with poor prognosis in several solid tumors make Trop2 an ideal target for oncology drugs. BAT8003 has shown promising potency and good tolerability/PK characteristics in pre-clinical studies, and is currently undergoing a phase I clinical trial in patients with Trop2-positive advanced epithelial cancers.

    BAT1308PD-1

    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.

    BAT4706CTLA-4

    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.

    BAT1006HER2

    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).

    BAT6026OX40

    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.

    BAT6005TIGIT

    BAT6005

    BAT6005 is a monoclonal antibody targeting TIGIT. TIGIT is an inhibitory immunoglobulin superfamily (IgSF) protein that is highly expressed on the surface of activated NK cell, CD4+ T cell and CD8+ T cell. The major ligand of TIGIT, CD155 (PVR), is highly expressed on the surface of many human solid tumor cells and dendritic cells (DCs). CD226 (DNAM-1) shares the ligand CD155 with TIGIT, and is an activating receptor that is highly expressed on the surface of NK cells and CD8+ T cells. TIGIT inhibits the activation of T cells or NK cells likely by multiple mechanisms:
    1) competitively binds CD155 with CD226
    2) directly prevents CD226 from dimerizing
    3) binds to CD155 on the cell surface of DCs, prompting IL-10 production and thus inhibiting T-cell activation

    BAT6021TIGIT

    BAT6021

    BAT6021 is an anti-TIGIT mAb candidate with afucosylated modification, resulting in higher level of ADCC activity. TIGIT is an inhibitory immunoglobulin superfamily (IgSF) protein that is highly expressed on the surface of activated NK cell, CD4+ T cell and CD8+ T cell. The major ligand of TIGIT, CD155 (PVR), is highly expressed on the surface of many human solid tumor cells and dendritic cells (DCs). CD226 (DNAM-1) shares the ligand CD155 with TIGIT, and is an activating receptor that is highly expressed on the surface of NK cells and CD8+ T cells. TIGIT inhibits the activation of T cells or NK cells likely by multiple mechanisms:
    1) competitively binds CD155 with CD226
    2) directly prevents CD226 from dimerizing
    3) binds to CD155 on the cell surface of DCs, prompting IL-10 production and thus inhibiting T-cell activation.
    As a fucose-free IgG1 antibody, BAT6021 can not only acts on the above mentioned mechanisms, but also depletes Treg cells with higher efficiency with the enhanced ADCC effect of antibody.

    BAT7104PD-L1/CD47

    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.

    BAT6030SIRPα

    BAT6030

    BAT6030 is a fully human monoclonal antibody drug candidate that binds to SIRPa and blocks its interaction with CD47 for the potential treatment of solid tumors and hematologic cancers including leukemia, non-hodgkin lymphoma. SIRP-α plays important role in cell tumor cell growth and proliferation. The interaction of SIRPα on macrophages with CD47 on tumor cells prevents killing of tumor cells by macrophages. BAT6030 binds specifically to SIRP-alpha and blocks the interaction with CD47 and promotes macrophage-mediated phagocytosis of tumor cells; in addition, BAT6030 also transforms immunosuppressive cells such as MDSC and TAM  in the tumor microvironment into non-suppressor cells which results in the reactivation of the immune system.

    BAT6019CD40

    BAT6019

    BAT6019 is a fully human agonistic antibody that binds to CD40 and activates antigen presenting cells (APCs), thereby enabling the APCs to boost the antitumor immune response by stimulating tumor-specific cytotoxic T cells; in addition, CD40 activation also promotes the production of immunostimulatory cytokines that further enhance T-cell activity, thereby activating and stimulating both innate and adaptive immunity, and enhancing the anti-tumor immune response.

    BAT1906IL-1β

    BAT1906

    BAT1906 is a recombinant anti-IL-1β fully human monoclonal antibody, and is intended for the combination with our I/O assets to treat solid tumors. The inflammation in tumor microenvironment can promote the accumulation of immunosuppressive cells (including regulatory T cells, myeloid-derived suppressor cells, macrophages and neutrophils, etc.). Under the stimulation of inflammatory mediators, tumor cells can maintain their own growth, invasion and migration, and recruit inflammatory cells by releasing various inflammatory factors and chemokines, and promote tumor growth. It can be seen that the tumor inflammatory response and inflammatory factors play a pivotal role in the occurrence, development, progression and invasion of tumors. Among them, the inflammatory cytokine interleukin-1β (IL-1β) is the main driving factor of the tumor inflammatory response. IL-1β occupies a dominant position in the tumor microenvironment, strongly induces the activity of myeloid-derived suppressor cells, and promotes the microenvironment of tumor formation and invasion. BAT1906 can target IL-1β to reduce immune suppression and promote anti-tumor activity.

Cardiovascular Disease
    BAT2094GPIIb/IIIa

    BAT2094

    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.

    BAT6024ANGPTL3

    BAT6024


    BAT6024 is a monospecific antibody against Angiopoietin-like 3 (ANGPTL3) and has the potential to treat cardiovascular diseases. ANGPTL3 is an inhibitor of LPL, and high levels of ANGPTL3 in human blood can lead to hypercholesterolemia and  hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia are associated with an increased risk of cardiovascular disease. ANGPTL3 inhibits the activity of lipoprotein lipase, which are involved in metabolism of lipoproteins, thus drives higher levels of plasma triglycerides, as well as low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, leading to increased risk of cardiovascular disease. 


Ophthalmology
    QLETLI®TNF-α

    QLETLI®

    QLETLI®, as the first approved biosimilar 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.

    BAT5906VEGF

    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.

    BAT4406FCD20

    BAT4406F

    BAT4406 is an investigational ADCC-enhanced anti-CD20 mAb candidate in clinical development for the treatment of B cell relative autoimmune diseases. BAT4406F is currently being evaluated in NMOSD, an orphan indication with an estimated prevalence of 0.5 to 10 per 100,000. We are currently initiating a phase I clinical trial for BAT4406F in China, and plan to complete this trial in 2022. BAT4406 binds specifically to CD20 on B-cells and kill B-cells by CDC, enhanced ADCC effect, and induction of apoptosis. 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.

Gastroenterology
    QLETLI®TNF-α

    QLETLI®

    QLETLI®, as the first approved biosimilar 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.