First in China: Boan Biotech’s Novel Investigational CD228-Directed ADC Approved for Clinical Trials

Yantai, July 25, 2024 – Boan Biotech today announced that its investigational drug candidate, a novel CD228-directed antibody drug conjugate (ADC) for injection codenamed BA1302, has been approved for clinical trials by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA). This is the first CD228-targeted investigational ADC drug candidate approved for clinical trials in China, intended for treating multiple types of solid tumors.

The only CD228-directed ADC under clinical development, which is highly expressed in multiple solid tumors

Initially identified in melanoma, CD228 is a GPI-anchored glycoprotein that plays a role in tumor cell proliferation and migration. It is highly expressed in a variety of solid tumors such as non-small cell lung cancer, breast cancer, melanoma, mesothelioma, colon cancer,  and pancreatic cancer, but has a low expression in normal tissues. Therefore, CD228 is highly specific in terms of its expression in tumors.

The antibody part of BA1302 is drived from BA-huMab^®, Boan Biotech’s proprietary human antibody transgenic mice. It binds with the membrane-bound form of CD228 only, not with sMF12, which is the soluble form of CD228. This high binding specificity reduces the non-specific binding, to ensure  higher efficacy and safety. The chemical part of BA1302 is BNLD11, a linker-payload screened by the company, which has remarkable stability both in vitro and in vivo. Structurally, approximately four BNLD11 molecules are conjugated to each antibody molecule on average. Such a design enhances the drug’s cell killing efficiency while minimizing the toxicity associated with payload release, thus striking a balance between therapeutic effects and adverse reactions.

Preclinical studies have shown that BA1302 is very potent in terms of internalization and bystander effect. It has the potential  to treat a broad spectrum of solid tumors as evidenced by its significant cytotoxicity against three types of cancers (i.e. lung cancer, gastric cancer, and melanoma) with CD228 expression ranging from low to high, as well as robust tumor suppression in patient-derived xenograft (PDX) models for multiple types of solid tumors. BA1302 has shown a prolonged half-life, favorable pharmacokinetics, and a good safety and tolerability profile in cynomolgus monkeys, indicating great promise for clinical use.

The clinical trial for BA1302 is a multicenter, open-label, multiple ascending dose and dose-expansion Phase I study. It aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of BA1302 for injection in patients with advanced solid tumors. To date, no other ADCs targeting CD228 has entered the clinical trial stage in China. BA1302 will be the only CD228-directed ADC in clinical stage in the world.

Developing more stable and effective ADC drugs on leading platforms

ADCs are drugs where antibodies and toxins are conjugated via linkers. They direct toxins towards target cells to kill them. This minimizes harm to normal cells and thus provides a wider therapeutic window. Leveraging its human antibody transgenic mouse and phage display platform, Boan Biotech is able to screen diverse antibodies fast and obtain antibodies with a lower immunogenicity risk. Building on this, the company has developed linker-payloads that are more stable and effective, and has built a better ADC platform, which covers the discovery and development processes of ADCs, and helps to get more candidates into the company’s pipeline.

In addition to the CD228-directed BA1302, Boan Biotech has another ADC codenamed BA1301, which targets Claudin18.2 and is undergoing a Phase I clinical trial. BA1301 is designed to treat advanced solid tumors expressing Claudin18.2, including advanced gastric cancer, gastroesophageal junction adenocarcinoma, and pancreatic cancer. The company also has multiple drug candidates under preclinical development, including bispecific ADCs.

“At Boan Biotech, innovation is a key driver for us,” said Dr. Dou Changlin, Chief Operating Officer and President of R&D at Boan Biotech. “We’ve built a strong competitive edge in terms of patents and technologies thanks to our well-established antibody development platform and the iterative development of ADC technology. This has laid a solid foundation for us to develop novel biologics efficiently.” He said that BA1302 is the second drug candidate from the company’s ADC platform and currently the only CD228-directed ADC undergoing clinical development in the world. Preclinical studies have shown that CD228 is highly expressed in various solid tumors, and BA1302 is a promising drug candidate either as a monotherapy or in combination with other drugs for treating a broad range of cancers, he added. “We’ll accelerate the clinical development of BA1302 and unleash its therapeutic potential, hoping to deliver a breakthrough therapy for cancer patients,” he said.