Huaota Biopharma Announces First Patient Dosed in Phase I Clinical Trial of HB0052, a Novel Anti-CD73 Antibody-Drug Conjugate (ADC)

Abstract

Recently,Zhejiang Huahai Pharmaceutical Co., Ltd. subsidiary, Shanghai Huaota Biopharmaceutical Co., Ltd. (hereinafter referred to as "Huaota")Announcement: Huaota Develops TargetedCD73Third-Generation Antibody-Drug Conjugates Targeting Antigens(ADC) ProjectHB0052Successful EntryIPhase Clinical Trial Stage`, and on`2024Year09Month04The first subject was enrolled and dosed at Shandong Cancer Hospital in China.。

This clinical study, led by Professor Lin Shen from Peking University Cancer Hospital, primarily aims to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of HB0052 in subjects with advanced solid tumors.Intended for the treatment of patients with advanced pancreatic cancer, advanced hepatocellular carcinoma, advanced gastric and gastroesophageal junction adenocarcinoma, and other advanced solid tumors.Phase I is planned to be conducted in 7 clinical centers in China, and Phase IIa is planned to be conducted in 15-20 centers in China.

AboutHB0052

CD73 antigen is expressed on various cells in the tumor microenvironment, including stromal cells, tumor cells, infiltrating immune cells, and epithelial cells, among others. It is particularly highly expressed in tumor cells and some infiltrating immune cells. In the tumor microenvironment, hypoxia induces the overexpression of CD73 on the surface of cancer cells, which hydrolyzes AMP into adenosine. Adenosine can suppress immune cell function and promote tumor growth. Blocking CD73 enzymatic activity with antibodies can eliminate its immunosuppressive function and enhance 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," and it exerts its enzymatic activity through the cyclic transition between the open and closed conformations (as shown in Figure 1).

Figure 1 Schematic diagram of CD73 catalyzing AMP to generate adenosine

HB0052 is the first third-generation antibody-drug conjugate (ADC) developed on Huaota’s antibody-drug conjugate platform, utilizing a topoisomerase inhibitor as the payload and targeting the CD73 antigen. This ADC molecule can simultaneously exert the immune system regulatory function mediated by the antibody and the cytotoxic effect of the small molecule toxin on tumor cells, demonstrating a synergistic anti-tumor effect. Preclinical animal model studies have shown excellent anti-tumor efficacy of HB0052; preclinical pharmacokinetic studies conducted in non-human primates indicate that HB0052 exhibits linear pharmacokinetic characteristics, good plasma stability, low non-specific cleavage, a long half-life, and favorable pharmacokinetic properties. Toxicology studies show that HB0052 has good safety and tolerability. HB0052 is expected to become a new generation of cancer treatment drug.

Figure 2 Mechanism of ADC drugs against tumors

Currently, China NMPAand the U.S. FDAAll have approved HB0052Entering the clinic。

Development Status of Similar Competitive Products

Currently, no drugs targeting CD73 have been marketed either in or outside China. Several monoclonal antibody projects are 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 these, Oleclumab (an anti-CD73 monoclonal antibody) developed by AstraZeneca is the most advanced, currently in Phase III trials for the treatment of unresectable NSCLC after concurrent chemoradiotherapy. HB0052, developed by Huaota, is the world’s second CD73-ADC drug to enter clinical trials.

About Huaota

Huaota Biopharmaceuticals is a biopharmaceutical company focused on independent research and development with a global perspective, specializing in the development of novel biologics for cancer, autoimmune diseases, and ocular conditions.Currently available11Project in the clinical stage: including entering the pivotal clinical trial, the first self-developed IL-36R in China targeting pustular psoriasis (a rare disease).Monoclonal antibody; and currently in clinical Phase IIIn the period, positive signals of PD-L1/VEGF have been observed in multiple tumor diseases such as endometrial cancer and non-small cell lung cancer.Dual Antibody; The First CD73-ADC with Dual Killing Effects Targeting Refractory TumorsAnd other core projects.

Huaota is currently actively seeking domestic and international partners to jointly advance and co-develop, aiming to provide high-quality, advanced biopharmaceuticals to the global market. These efforts are intended to meet the needs of a broad patient base for accessible and affordable biologics, with a commitment to changing the world through innovation!