BioInnovate's $2.94B Bispecific ADC IDE034 Achieves Global Out-Licensing Milestone with IDEAYA

On November 11, Biocytogen Pharmaceuticals (Beijing) Co., Ltd. announced that IDEAYA Biosciences had exercised its option to obtain the exclusive global license for BCG034 (IDE034), a potential first-in-class bispecific antibody-drug conjugate (BsADC) targeting B7H3 and PTK7 with a topoisomerase inhibitor payload, and nominated the project as a development candidate.

Subject to the completion of current preclinical and IND-enabling studies, IDEAYA plans to submit an Investigational New Drug (IND) application for IDE034 to the U.S. FDA in 2025 to initiate first-in-human trials.

Under the option and license agreement between Biocytogen and IDEAYA, Biocytogen will receive an upfront payment and option exercise fees, development and regulatory milestone payments, commercialization milestone payments, and royalties on net sales, totaling up to $406.5 million (approximately RMB 2.94 billion), including $100 million in clinical development and regulatory milestone payments.

Biocytogen is an international biotechnology company driven by innovative technologies for new drug development. Based on gene-editing technology, the company leverages its proprietary genetically engineered RenMice® (RenMab®, RenLite®, RenNano®, RenTCR-mimic™) platform to discover fully human therapeutic monoclonal antibodies, bispecific/multispecific antibodies, bispecific antibody-drug conjugates (ADCs), nanobodies, and TCR-like antibodies.

Currently, Biocytogen is conducting large-scale drug development targeting over 1,000 potentially druggable targets under its “Thousand Mice, Ten Thousand Antibodies” initiative, and has established a library of more than 400,000 fully human antibody sequences for global collaboration.

As of December 31, 2023, Biocytogen had signed 103 agreements for collaborative drug development, licensing, or transfer, and reached licensing and development collaborations on 47 target projects via its RenMice® platform with enterprises including multiple multinational corporations (MNCs). Additionally, several clinical-stage antibody molecules have been licensed out through external collaboration agreements.

The IDE034 (BCG034) involved in this transaction is an antibody-drug conjugate (ADC) prepared from a fully human common light chain B7H3/PTK7 bispecific antibody, which was screened using Biocytogen’s proprietary RenLite technology platform.

B7-H3 and PTK7 are two tumor-associated antigens. According to the Human Protein Atlas database, B7-H3 and PTK7 are co-expressed in various types of solid tumors, with co-expression rates of approximately 30%, 46%, and 27% in lung cancer, colorectal cancer, and head and neck cancer, respectively. They are also closely associated with tumor invasion, metastasis, and poor prognosis, making them promising new anti-cancer targets that have garnered significant attention in recent years.

Currently, inhibitors targeting B7-H3/PTK7, including antibodies, antibody-drug conjugates (ADCs), and radioimmunotherapy, represent a novel class of antitumor agents. Several investigational drugs targeting B7-H3/PTK7 have demonstrated preliminary clinical efficacy.

By targeting these specific antigens, Biocytogen is developing this B7H3/PTK7 inhibitor using its proprietary topoisomerase inhibition technology. Topoisomerases are key enzymes within cells responsible for DNA replication, repair, and unwinding; inhibiting their activity can effectively block tumor cell proliferation. Leveraging its proprietary topoisomerase I linker-payload, Biocytogen enables this drug to bind precisely to the surfaces of B7H3 and PTK7, thereby maximizing target specificity and drug potency.

Previously, IDEAYA also disclosed detailed structural information on its B7H3/PTK7-targeted bispecific antibody-drug conjugate (BsADC) program at an investor conference. Based on preclinical data, this potential first-in-class BsADC program, featuring a B7H3/PTK7-targeted topoisomerase inhibitor payload, may be developed as a monotherapy or in combination with multiple DDR-targeted programs in IDEAYA’s pipeline, including the PARG inhibitor IDE161.

Dr. Shen Yuelei, Chairman and CEO of Biocytogen, stated, “We are delighted that IDEAYA has decided to exercise its option to secure the exclusive global license for our B7H3/PTK7 BsADC program, IDE034, which incorporates our proprietary topoisomerase linker-payload technology. This significant milestone further validates the capabilities of Biocytogen’s RenLite® platform, bringing us one step closer to delivering impactful therapies for patients with solid tumors. We look forward to supporting IDEAYA in advancing this program into the clinical stage.”

Dr. Michael White, Chief Scientific Officer of IDEAYA Biosciences, stated: “We are pleased to nominate IDE034 as a development candidate. This B7H3/PTK7-directed bispecific antibody-drug conjugate (BsADC), featuring a first-in-class topoisomerase inhibitor payload, has demonstrated significant tumor regression in preclinical models. The high co-expression of B7H3 and PTK7 in solid tumors such as lung cancer, colorectal cancer, and head and neck cancer underscores its potential as both a monotherapy and in combination with our PARG inhibitor, IDE161.”

In recent years, Chinese pharmaceutical companies have rapidly advanced in the field of bispecific antibody drugs, with multiple domestically produced bispecific antibodies achieving significant progress not only in China but also realizing important business development in international markets.

For example, in December 2022, Akeso entered into a collaboration and license agreement with Summit Therapeutics for ivonescimab, a PD-1/VEGF bispecific antibody, featuring an upfront payment of $500 million and a total potential deal value of up to $5 billion. As a leader in this field, Akeso has successfully launched two bispecific antibody drugs it developed: cadonilimab and ivonescimab. Furthermore, ivonescimab demonstrated superior efficacy in pivotal Phase III clinical trials, further enhancing its competitiveness in the global market.

YiMing Angio and Tongrun Biologics have also achieved significant business development (BD) milestones in the bispecific antibody field. In early August 2024, YiMing Angio licensed the rights to its PD-L1/VEGF bispecific antibody IMM2510 and next-generation CTLA-4 antibody IMM27M outside Greater China to Instil Bio, in a deal valued at over $2 billion. In late August, YiMing Angio received a $10 million upfront payment.

On August 9, 2024, Merck & Co. reached an agreement with Tongrun Biopharma to acquire global rights to the CD3/CD19 bispecific antibody CN201, paying a $700 million upfront fee.

Furthermore, BioNTech licensed Promiscence Biologics’ PD-L1/VEGF bispecific antibody PM8002 for over $1 billion, further validating the market potential of this class of therapeutics.

In addition to companies that have already secured business development (BD) deals, 3SBio, RemeGen, Junshi Biosciences, and SinoCellTech are also actively advancing the research, development, and clinical trials of their bispecific antibody drugs. These agents target multiple high-profile pathways, including PD-1/VEGF, and have demonstrated favorable efficacy and safety profiles in clinical studies. As these therapies gradually enter the market, Chinese bispecific antibodies are expected to assume a more prominent role in the global pharmaceutical industry over the coming years, offering patients additional effective treatment options.

As a novel therapeutic modality, antibody-drug conjugates (ADCs) offer significant advantages over monoclonal antibodies, bispecific antibodies, and chemotherapy, further expanding and deepening the application of targeted therapies. Particularly in the field of oncology, the continuous growth in ADC development is ushering in a new era of targeted treatment.

A new trend is that bispecific antibody-drug conjugates (BsADCs), as an emerging technological direction, are particularly popular among domestically developed bispecific antibodies that have successfully expanded into overseas markets.

The focus of the transaction between Biocytogen and IDEAYA is on bispecific antibody-drug conjugates (bsADCs). This is because bsADCs offer several advantages over monoclonal antibody-drug conjugates (mAb-ADCs). With two antigen-binding sites, bsADCs can enhance tumor cell killing by simultaneously binding to both tumor cells and immune cells. Furthermore, by targeting two different cellular epitopes, bsADCs can reduce off-target side effects. The dual-targeting capability also enables the blockade of two distinct signaling pathways, thereby enhancing cytotoxicity and overcoming drug resistance.

The bispecific antibody-drug conjugate (ADC) sector has also witnessed a record-breaking major business development (BD) deal by Baili Tianheng. On December 11, 2023, Baili Tianheng entered into an $8.4 billion collaboration with Bristol Myers Squibb (BMS) for its HER3/EGFR bispecific ADC candidate, BL-B01D1. This transaction set a new record for the highest upfront payment in the global licensing-out of innovative Chinese pharmaceuticals.

From the perspective of the global distribution of bispecific antibody-drug conjugate (BsADC) pipelines under development, BsADCs may represent a key therapeutic area where Chinese pharmaceutical companies are leading their overseas counterparts. Data from the Insight database shows that as of May 2024, only 16 BsADC candidates had entered clinical stages globally, with the majority being developed by Chinese pharmaceutical companies, including Baili Tianheng, Alphamab Oncology, Chia Tai Tianqing, and Innovent Biologics.

Furthermore, as monoclonal antibody-based ADCs in clinical stages are increasingly being licensed or acquired, future ADC transactions will shift more toward bispecific antibody-based ADC projects.

As one of the hottest tracks for innovative drugs, numerous domestic pharmaceutical companies have entered the bispecific antibody-drug conjugate (BsADC) field, ushering in a period of robust growth. With an increasing number of transactions being finalized, the potential of Chinese BsADC drugs is gradually coming to light. It is believed that more differentiated, China-made BsADC products will enter the global market in the future.