Huaota Announces NMPA Approval of HB0046, the World’s First CD39/CD73 Bispecific Antibody, for Clinical Trials
Huaota
Biological New Drug Developer
Huahai Pharmaceutical
Medical and Health Product Provider
Recently,Shanghai Huaota Biopharmaceutical Co., Ltd., a subsidiary of Huahai Pharmaceutical Co., Ltd.(hereinafter referred to as "Huaota") receivedNMPANotice, ConsentHuaota's Self-Developed Bispecific Antibody Project HB0046 Targeting CD39 and CD73 Enters Clinical Trials。
HB0046 is aFirst-in-ClassInnovative Immune Checkpoint Inhibitors: Preclinical Studies ShowShowing application potential in multiple tumor indicationsHB0046 molecule possessesGood safety and antitumor effects, along with excellent CMC properties, is expected to benefit a wide range of cancer patients in clinical practice, especially those who are resistant or unresponsive to PD-1/PD-L1 treatment. Dr. Zhu Xiangyang, General Manager of Huaota, expressed his anticipation and hopes that HB0046 will initiate clinical research as soon as possible to benefit a broad population of cancer patients. Meanwhile, the approval of HB0046 marksHuaota Further Establishes and Improves Nanobody Screening and Bispecific Antibody Design Platform`, laying the foundation for the subsequent development of more clinically valuable bispecific (multispecific) antibodies.`
ATP(Adenosine Triphosphate)-The adenosine pathway is one of the key immune regulatory mechanisms in the tumor microenvironment. CD39 and CD73 proteins are crucial enzymes affecting this pathway, widely expressed in the tumor microenvironment, particularly highly expressed in tumor cells and immune cells. CD39 converts immunostimulatory ATP into AMP.(Adenosine Monophosphate), CD73 catalyzes the conversion of AMP into adenosine, which can inhibit the function of immune cells by binding to receptors on their surface, thereby promoting tumor growth. Studies have shownSimultaneous blockade of CD39 and CD73 synergistically enhances anti-tumor effects。
The CD73 protein consists of three domains: the N-terminal domain contains two zinc ion binding sites, the C-terminal domain contains the substrate AMP binding site, and the N-terminal and C-terminal domains are connected by a short helix, which controls the movement of CD73.CD73 has two conformations: "open" and "closed"., CD73 exerts its enzymatic activity through the cyclic transition between open and closed conformations (as shown in Figure 1).
Figure 1 Schematic diagram of CD73 catalyzing AMP to generate adenosine
Unlike CD73, which exists as a dimer, CD39 is a monomeric enzyme (light blue cartoon structure) that can catalyze ATP (green rod structure) to generate AMP with the help of magnesium ions (green spheres) (as shown in Figure 2).
Figure 2 Schematic diagram of CD39 and ATP complex structure (predicted by AlphaFold 3)
HB0046 is based onHuaota Hybridoma and Nanobody Screening PlatformAn independently developed bispecific antibody composed of anti-CD39 VHH(Heavy Chain Variable Region)Fragments and anti-CD73 monoclonal antibodies are linked together. This bispecific antibodyBoth CD39 and CD73 maintain high affinity, and can effectively inhibit the enzymatic activity of membrane-bound and soluble CD39 and CD73,Demonstrates significant synergistic effects in the enzymatic inhibition of CD39 and CD73 as well as ATP-mediated T cell proliferation suppression.Multiple solid tumor and hematological tumor models demonstrate the excellent anti-tumor effects of HB0046; preclinical trials conducted in non-human primates show that HB0046 exhibits non-linear pharmacokinetic characteristics with good plasma stability., with a long half-life and satisfactory pharmacokinetic properties; Toxicology studies show HB0046Good safety and tolerability。
Currently, no drugs targeting CD39 or CD73 have been marketed either in China or globally. Several antibody and ADC projects are currently in clinical research stages, with indications under development including solid tumors such as non-small cell lung cancer, breast cancer, pancreatic cancer, and prostate cancer. Among them, Oleclumab, developed by AstraZeneca.(Anti-CD73 Monoclonal Antibody)The fastest-progressing one is currently in Phase III clinical stage, used for unresectable NSCLC after concurrent chemoradiotherapy.(Non-Small Cell Lung Cancer)Treatment.Huaota's HB0046 is the world's first bispecific antibody targeting CD39/CD73 to enter clinical stage.
Huaota Biopharmaceutical is a biopharmaceutical R&D enterprise that focuses on independent development and has a global perspective. It specializes in the R&D of biological new drugs in the fields of oncology, autoimmune diseases, and fundus diseases.Currently, there are 11 projects in clinical stages: including the IL-36R monoclonal antibody, which has entered a pivotal clinical trial as the first domestically self-developed treatment in China for pustular psoriasis (a rare disease); the PD-L1/VEGF bispecific antibody currently in Phase II clinical trials, showing positive signals in multiple tumor diseases such as endometrial cancer and non-small cell lung cancer; and the core project CD73-ADC, the first with dual killing effects targeting refractory tumors.。
Huaota is currently actively seeking domestic and international partners to jointly advance and co-develop, with the aim of providing high-quality, cutting-edge biopharmaceuticals to the global market. This effort seeks to meet the widespread patient demand for accessible and affordable biologics, fulfilling the vision of innovation changing the world!