Biokin Pharmaceutical's Iza-bren triggers $1.05B BMS milestone, redefining China's biotech playbook

As a landmark business development case in the history of China's biotech industry, Biokin Pharmaceutical entered into an exclusive licensing agreement with Bristol Myers Squibb (BMS) at the end of 2023. The agreement features a non-refundable and non-creditable upfront payment of $800 million, with a potential total transaction value of up to $8.4 billion. Beyond the record-breaking financial terms, the most significant aspect is that Biokin did not relinquish its rights in the U.S. market—the most critical region for innovative drug commercialization. Instead, the company opted to co-develop the asset with BMS, sharing both costs and profits.

In terms of transaction structure, this type of global partnership resembles the model previously established between Legend Biotech and Johnson & Johnson. It implies that Biokin will secure a higher proportion of profit sharing in the U.S. market. In an earlier interview with VCBeat, Dr. Zhu Yi, founder of Biokin Pharmaceutical, emphasized that the ultimate goal of collaborating with multinational corporations is to build up Biokin's global development and commercialization capabilities through the partnership, thereby enabling the company to eventually operate its own product pipeline independently.

The success of Iza-bren stands as clear evidence of Biokin's advancing global strategy. In another strategic move, on the evening of September 29, Biokin Pharmaceutical submitted its listing application to the Hong Kong Stock Exchange for the third time, seeking a dual primary listing (A+H) with Goldman Sachs, J.P. Morgan, and Citi acting as joint sponsors. This step reinforces the company's pursuit of its strategic path to become "a leading multinational corporation focused on the oncology field."

In 1996, its predecessor, Baili Pharma, established a manufacturing facility in Wenjiang, building its foundational business with generic drugs and traditional Chinese medicines. In 2010, founder Dr. Zhu Yi initiated a strategic transformation, channeling all profits from generics into innovative drug R&D. In 2014, Biokin Pharmaceutical founded its U.S. subsidiary, SystImmune, in Seattle, focusing on ADC research and adopting a "For Global" strategy to pave the way for future international product commercialization and global market expansion.

The successful global advancement of Iza-bren rests on three pillars: innovation, data, and business development (BD) negotiations.

Back in 2014, when ADC innovation was still an emerging frontier, Biokin Pharmaceutical was already pioneering the field of bispecific ADCs. Leveraging its proprietary HIRE ADC platform, the company designed Iza-bren with a unique structure—an EGFR×HER3 bispecific antibody conjugated with a dual-payload topoisomerase I inhibitor.

Iza-bren is composed of an EGFR/HER3 bispecific antibody, a cathepsin B-cleavable linker, and a TOP-1 inhibitor payload (ED04), achieving a high drug-to-antibody ratio (DAR) of 8. The molecule exhibits a potent bystander effect, enabling efficient elimination of adjacent heterogeneous tumor cells. Furthermore, it simultaneously targets both EGFR homodimers and EGFR/HER3 heterodimers on tumor cells, enhancing targeting precision and generating stronger, more durable anti-tumor activity. This profile underscores its potential as a "broad-spectrum anti-tumor solution."

The macromolecular component is the bispecific antibody SI-B001, which specifically targets and binds to both EGFR and HER3 on tumor cells, ensuring precise targeting. Due to its unique structural characteristics, SI-B001 does not directly bind to HER3, thereby avoiding inhibition of targets essential for maintaining normal physiological functions. This mechanism contributes to the molecule's favorable safety profile with low toxicity and minimal side effects.

The small molecule toxin component is ED04, a camptothecin analog independently developed by Biokin Pharmaceutical. It directly kills tumor cells by disrupting DNA structure. ED04 prevents the rejoining of broken DNA strands, thereby inhibiting DNA replication and RNA synthesis to suppress tumor growth.

In the payload segment, Iza-bren utilizes Biokin's proprietary Ac linker technology. This linker offers superior stability, effectively preventing premature drug molecule release and ensuring toxin stability during systemic circulation. Additionally, the antibody conjugate formed with the Ac linker demonstrates improved hydrophilicity and reduced aggregation tendency, resulting in enhanced safety profiles and superior anti-tumor efficacy in vivo.

In 2023, Iza-bren made a significant impact on the global innovative drug market with compelling clinical data.

The first-in-human Phase I data presented at ASCO revealed an objective response rate (ORR) of 61.8% and a disease control rate (DCR) of 91.2% in 34 patients with EGFR-mutant NSCLC. Among 42 patients with EGFR wild-type NSCLC, the ORR was 40.5% with a DCR of 95.2%. Additionally, Iza-bren demonstrated outstanding efficacy in small cell lung cancer, head and neck squamous cell carcinoma, and esophageal cancer.

Following the ASCO data presentation, eight of the world's top ten multinational pharmaceutical companies expressed interest in collaborating with Biokin Pharmaceutical. Dr. Zhu Yi noted that nearly all of the global top 20 MNCs had engaged in initial discussions, with several progressing to formal offers. From the outset, Iza-bren was conceived as a global program, with Biokin insisting on a co-development, cost-sharing, and profit-sharing partnership model.

"We required MNCs to first agree to our transaction structure. Some directly stated they couldn't accept our terms. We remained patient, sometimes even making concessions on specific clauses, but never compromising on the core structure. When counterparts hesitated, we suggested they step back and observe, deciding whether to proceed only after other negotiations concluded. Some companies gradually withdrew as they didn't want this structure; others directly declined. But looking back, our persistence proved justified—they were dealing with a company capable of competing globally, one with product competitiveness, team vision, and decisive leadership."

Robust product data served as both leverage and foundation in negotiations with MNCs, though generating such data requires substantial funding. In January 2023, Biokin Pharmaceutical listed on the STAR Market with an issue price of 24.7 yuan per share and a market capitalization of approximately 10 billion yuan. Its subsequent stock surge provided crucial financial support for accumulating pivotal clinical data. "Our negotiations with BMS were backed by compelling clinical data from over 800 patients across more than ten tumor types, demonstrating both promising efficacy and manageable safety. A transaction built on this data foundation inherently deserved this valuation—or even higher."

At the 2025 World Conference on Lung Cancer (WCLC), Iza-bren combined with osimertinib as a first-line treatment for EGFR-mutant NSCLC demonstrated a 100% objective response rate (ORR) and significantly prolonged progression-free survival (PFS). As a monotherapy for EGFR-TKI resistant patients, it achieved a median PFS of 12.5 months. In a cohort of 24 nasopharyngeal carcinoma patients, the ORR was 45.8% with a disease control rate (DCR) of 100%.

By the end of 2024, Iza-bren had initiated over 40 clinical trials globally, including nine Phase III registration trials in China, and secured seven Breakthrough Therapy Designations across six major cancer types. Among these, the nasopharyngeal carcinoma and esophageal squamous cell carcinoma indications are expected to submit New Drug Applications (NDAs) to China's NMPA in the second half of 2025, with nasopharyngeal carcinoma likely to be the first to reach the approval milestone.

On July 2, Iza-bren met the primary endpoint in its pivotal Phase III trial for nasopharyngeal carcinoma (BL-B01D1-303), becoming the world's first bispecific ADC to complete Phase III clinical study.

For BMS, Iza-bren represents both a potential blockbuster oncology drug with broad-spectrum capabilities and a new revenue stream—with possible combination strategies—as it faces the patent cliff of Opdivo (nivolumab). In China, core patents for Opdivo are projected to expire around 2026, subject to potential regulatory extensions. In the U.S., BMS has successfully extended patent protection until 2028 through the introduction of new formulations (subcutaneous delivery) and additional indication development.

Over the past five years, BMS has extensively explored combining Opdivo with nearly every conceivable approach: immune targets, chemotherapy, anti-angiogenic agents, ADCs, cell therapies, and delivery systems. This includes early strategies such as O+Y ("dual immunotherapy"), which leveraged two immune checkpoint inhibitors to achieve synergistic and enhanced immune activation, as well as the $11.1 billion collaboration with BioNTech to co-develop PD-1/VEGF bispecific candidate (PM8002/BNT327) and plan head-to-head or sequential combination regimens with Opdivo.

Along this strategic path, Biokin Pharmaceutical has already initiated exploratory studies—its "BL-B01D1 + PD-1 monoclonal antibody ± chemotherapy" combination regimen has secured multiple Phase II clinical trial approvals in China. These trials cover non-small cell lung cancer, advanced gastric cancer, advanced small cell lung cancer, triple-negative breast cancer, advanced urothelial carcinoma, advanced esophageal squamous cell carcinoma, advanced head and neck squamous cell carcinoma, and advanced nasopharyngeal carcinoma.

Even before investigating combination efficacy, Iza-bren's outstanding monotherapy performance already addresses core challenges in current immunotherapy—specifically, primary resistance in certain patient populations and acquired resistance in others. By building upon existing immune checkpoint blockade mechanisms and introducing innovative targeting through novel bispecific molecular design, Iza-bren demonstrates potential to break through existing immunotherapy bottlenecks and expand therapeutic benefits into tumor types with limited current options.

For BMS, Iza-bren represents a critical growth driver to offset the patent cliff of Opdivo and reinvigorate its immuno-oncology portfolio amid slowing growth.

On August 18, Iza-bren received its first Breakthrough Therapy Designation in the United States for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitutions, who have previously received EGFR-TKI and platinum-based chemotherapy. This designation was supported by positive data from three clinical studies: the China-based BL-B01D1-101 and BL-B01D1-203 trials, and the global multi-center study BL-B01D1-LUNG-101, which includes sites in the United States, European Union, and Japan.

Currently, Iza-bren is being evaluated in 40 clinical trials worldwide, covering multiple solid tumors including NSCLC, small cell lung cancer (SCLC), nasopharyngeal carcinoma, breast cancer, urothelial carcinoma, and esophageal cancer. In 2025, Biokin Pharmaceutical and BMS jointly initiated three global Phase II/III clinical trials, demonstrating continued acceleration of overseas development. According to BMS projections, BL-B01D1 is expected to launch in the U.S. market around 2028.

Upon successful commercialization of Iza-bren, Biokin Pharmaceutical will enter a phase of commercial execution and value realization. As Dr. Zhu Yi previously stated, "If you have the capabilities, you don't need to license-out—you can develop and commercialize independently. Once you become a global company, licensing-out may no longer be necessary."

Returning to its founding vision, Biokin aims to "become a leading multinational corporation focused on oncology within a decade, delivering breakthrough impact in cancer treatment"—and is consistently executing toward this goal. The company seeks to leverage partnerships with established MNCs precisely to build the capacity to emerge as an MNC itself. China's innovative drug sector awaits the arrival of precisely such a milestone.