We have built a broad and sustainable pipeline through partnerships with global biopharmaceutical companies. Our mission is to transform patients’ lives in China and eventually leverage our capabilities to impact human health worldwide.
Niraparib (ZL-2306) is a highly potent and selective oral, once-daily small molecule poly (ADP-ribose) polymerase 1/2, or PARP 1/2, inhibitor with the potential to be a first-in-class drug for treatment across multiple solid tumor types in China. We obtained an exclusive license for the development and commercialization of niraparib in China, Hong Kong and Macau in 2016. In March 2017, niraparib was approved by the FDA as a maintenance treatment for women with recurrent platinum-sensitive ovarian cancer. We believe that niraparib represents a significant market opportunity in China, given its differentiated clinical profile, demonstrated clinical relevance to multiple solid tumor types, potential to provide a notable improvement to existing standards of care, and prospects to be utilized in multiple combination and monotherapy treatment options. We are currently evaluating niraparib in several malignancies, including ovarian cancer, breast cancer etc. and will also explore combination studies in relevant indications.
Mechanism of Action
PARP is a family of proteins playing key roles in DNA repair pathway. PARP inhibitors appear most effective when used to treat tumors with underlying defects in DNA repair, such as BRCA1 and BRCA2, or when combined with another DNA-damaging agent. PARP inhibitors also have an additional mechanism of action known as “PARP trapping”, the effect of which is to poison DNA by stabilizing PARP-1 and PARP-2 at sites of DNA damage, generating complexes that may be even more toxic than the unrepaired single-strand breaks which result from PARP inhibition. T.
ZL-2401 (Omadacycline) is a once-daily oral and intravenous (IV) broad-spectrum antibiotic in a new class of tetracycline derivatives, known as aminomethylcyclines. We sub-licensed rights in China, Hong Kong, Macau and Taiwan from Paratek. Omadacycline has been designed to address tetracycline resistance, and is being developed for acute bacterial skin/skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP) and urinary tract infections (UTIs). Two pivotal Phase III studies of omadacycline in ABSSSI and CABP have achieved their primary endpoints. Omadacycline has been granted Qualified Infectious Disease Product (QIDP) status in the United States, and Fast Track status by the FDA.
Mechanism of Action
Antibiotic resistance has become a significant public health challenge andthere is an increasing need for effective, well-tolerated antibiotics. ZL-2401 (Omadacycline) has been designed to overcome the two major mechanisms of tetracycline resistance, known as pump efflux and ribosome protection. Omadacycline has a broad microbiologic profile with effective microbiological activity against a broad spectrum of pathogens, including problem pathogens like MRSA and PRSP, Gram-negative pathogens such as H. influenzae and atypical bacteria such as Legionella. It has strong activity against most of the pathogens encountered in the indications pursued, ABSSSI, CABP and UTI. It has useful activity against Acinetobacter, a multi-drug resistant pathogen in the health care setting which is frequently encountered in Chinese hospitals.
Bemarituzumab (FPA144) is a first-in-class isoform-selective, humanized monoclonal antibody in clinical development as a targeted immuno-therapy for tumors that overexpress FGFR2b, including gastric and gastro-esophageal junction cancer. China has one of the highest incidence rates of gastric cancer in the world, with approximately 680,000 new cases annually.1,2 The randomized, controlled Phase 3 portion of the FIGHT trial evaluating Bemarituzumab plus mFOLFOX6 is expected to start in the second half of 2018 and would serve as a global registrational study for the treatment of front-line gastric and gastro-esophageal junction cancers.
Bemarituzumab has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells.Bemarituzumab is being evaluated as a potential treatment for gastric cancer. In a Phase 1 trial,Bemarituzumab demonstrated monotherapy activity in heavily pre-treated patients with FGFR2b-positive gastric cancer and did not exhibit certain toxicities that have been seen with less selective FGFR2 small molecule therapeutics. FGFR2b is a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. An estimated 10% of patients with gastric cancer have tumors that overexpress FGFR2b or have FGFR2 gene amplification, which is associated with poor prognosis.
ZL-2301 is an oral, small molecule dual target tyrosine kinase inhibitor, or TKI, that we have an exclusive license for in China, Hong Kong, Macau and Taiwan from Bristol Myers Squibb.ZL-2301 has been tested in 4 phase III studies in hepatocellular cancer and showed anti-tumor activity and manageable drug safety. Based on our review of the results from Bristol-Myers Squibb’s development program for ZL-2301, our understanding of the etiology and current standard of care of HCC in Chinese patients and our ongoing research, we believe that ZL-2301 has the potential to be an effective treatment option for Chinese HCC patients and merits further clinical trials. In the second quarter of 2017 we initiated a Phase II trial of ZL-2301 as a second-line treatment for advanced HCC patients in China.
Mechanism of Action
ZL-2301 is a dual target tyrosine kinase inhibitor, or TKI, which blocks both vascular endothelial growth factor receptor, or VEGFR, and fibroblast growth factor receptor, or FGFR. The mechanism of action of tyrosine kinase inhibitors includes modulation of key pathways and mechanisms of angiogenesis, the formation of new blood vessels in human body, and tumorigenesis, the formation of cancers. VEGF plays a key role in tumor angiogenesis and aberrations in VEGFR have been shown to have potential in driving tumor growth, promoting angiogenesis, and conferring resistance mechanisms to anti-cancer therapies.
Fugan (ZL-3101) is a novel steroid-sparing topical product for the treatment of eczema and psoriasis. We licensed the exclusive worldwide rights to fugan in 2016 from GSK. We believe fugan could offer a natural, topical, steroid-sparing product with strong efficacy and limited long-term safety concerns, at a more attractive price point, compared to global competitors. A Phase II study in patients with mild to moderate subacute eczema was started in China in the second quarter of 2017.
Mechanism of Action
Eczema, also called dermatitis, is a group of diseases that results in inflammation of the skin. The potential anti-inflammatory benefit of fugan results from its active botanical formula which incorporates the herbs Glycyrrhizae Radix et Rhizoma and Sophorae Flavescentis.
Tumor Treating Fields (Optune)
Optune, a portable device that delivers tumor treating fields (TTFields), is a novel cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division leading to inhibition of tumor growth death of tumor cells. Optune is currently marketed in the United States, the European Union, Switzerland, Japan and certain other countries for the treatment of adult newly diagnosed or recurrent GBM and is in advanced clinical development for multiple additional solid tumor indications. In multiple Phase II trials, TTFields demonstrated marked efficacy results and safety profile in NSCLC, pancreatic cancer and malignant mesothelioma. In 2018, we obtained an exclusive license to commercialize Optune in mainland China, Hong Kong, Macau and Taiwan from Novocure Inc. (Novocure). In addition to GBM, we will collaborate with Novocure on development activities for TTFields in multiple solid tumor indications, including on Novocure's ongoing Phase III pivotal trials in NSCLC and pancreatic cancer and a Phase III pivotal trial in ovarian cancer that is planned to open later this year.
Mechanism of Action
TTFields is a novel technology platform developed for cancer therapy. It uses alternating electric fields tuned to specific frequencies to target cancer cells by disrupting cell division, inhibiting tumor growth and causing affected cancer cells to die. The electric fields have impact on highly charged and polar proteins such as tubulin and septin which are critical for normal cell division (mitosis). During normal cell division, tubulin and septin must position themselves in a particular way in order for the cell to divide. TTFields exerts forces on tubulin and septin, preventing them from moving to their correct locations leading to disruption of cancer cell division.
At the specific frequency tested, TTFields do not seem to affect healthy cells. Mild to moderate skin irritation is the most common side effect reported.
Margetuximab is an Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2, or HER2. HER2 is expressed on tumor cells in breast, gastric and other types of solid tumors, making it a key target for biologic therapy. Margetuximab is currently being studied as a potential treatment for metastatic breast cancer and advanced gastric cancer. In November 2018, Zai Lab obtained regional development and commercialization rights of Margetuximab in mainland China, Hong Kong, Macau and Taiwan from MacroGenics company.
Mechanism of Action
Margetuximab is believed to mediate its therapeutic activity against HER2+ tumors by a combination of mechanisms including:
• Modulation of HER2 signaling, resulting in growth retardation or the induction of apoptosis, or cell death;
• Enhanced ADCC through increased binding of margetuximab to immune cells that bear type III Fcg receptors leading to destruction of HER2+ tumor cells.
MGD013 is a bispecific monoclonal antibody. It is anticipated that MGD013 could be used for the treatment of a wide range of cancers, including both solid tumors and hematological malignancies. A Phase I dose escalation study of MGD013 is ongoing. In November 2018, Zai Lab obtained regional development and commercialization rights of MGD013 in mainland China, Hong Kong, Macau and Taiwan from MacroGenics company.
ZL-1101 is an anti-OX40 antagonistic antibody with first-in-class potential for the treatment of a range of autoimmune diseases such as graft-versus-host disease or systemic lupus erythematosus. We licensed the exclusive worldwide rights to ZL-1101 from UCB in 2015.We intend to file an IND in 2018.
Mechanism of Action
OX40, also known as CD134, TNFRSF4, ACT35 or TXGP1L, is a member of the TNF receptor superfamily, a group of ligands and receptors involved in diverse biological processes. OX40 is predominantly expressed on activated T-cells, and its cognate ligand, OX40L, is expressed on activated antigen presenting cells. When immune activation is excessive or uncontrolled, pathological allergy, asthma, inflammation, autoimmune and other related diseases may occur. Because OX40 functions to enhance immune responses, it may exacerbate autoimmune and inflammatory diseases, and therefore drugs which block or suppress OX40 have the potential to treat a range of such disorders.
ETX2514 SUL is a novel broad-spectrum intravenous inhibitor of class A, C and D beta-lactamases. ETX2514 restores the in vitro activity of multiple β-lactams against Gram-negative, multidrug-resistant pathogens. Entasis is initially developing ETX2514SUL, a fixed-dose combination of ETX2514 and sulbactam, for the treatment of a variety of serious multidrug-resistant infections caused by A. baumannii. Sulbactam is a generic β-lactam that has intrinsic activity against A. baumannii but suffers from widespread β-lactamase-mediated resistance. In preclinical studies, ETX2514 restored sulbactam antibacterial activity against A. baumannii. ETX2514 has completed single- and multi-ascending dose Phase 1 trials. The U.S. Food and Drug Administration has granted Qualified Infectious Disease Product (QIDP) designation and Fast Track designation to ETX2514SUL for the treatment of hospital-acquired and ventilator-acquired bacterial pneumonia and bloodstream infections due to A. baumannii.