This is not the first collaboration between Yilian Biotech and Roche.

In January 2024, Yilian Biotech and Roche entered into a global collaboration and license agreement for YL211, a c-Met-targeted antibody-drug conjugate (ADC). Under the agreement, Roche is required to pay an upfront payment and near-term milestone payments totaling $50 million, plus potential milestone payments of up to $1 billion, as well as tiered royalties based on future global annual net sales.

The recent partnership for the YL201 program is built on the success of this prior collaboration.

Both YL211 and YL201 are developed based on Yilian Biotech’s proprietary TMALIN technology platform.

The biggest limitation in traditional ADC development is that the drug must penetrate the tumor cell membrane to exert its efficacy, which gives rise to challenges such as a scarcity of eligible antibodies, unstable delivery, and poor penetration in solid tumors.

The core breakthrough of the TMALIN platform lies in its ability to achieve extracellular cleavage in the tumor microenvironment. This means that regardless of antibody internalization capacity, the ADC retains high anti-tumor activity, greatly expanding the range of selectable antibodies. Its unique toxin-linker design promotes drug accumulation in the tumor microenvironment, enhancing local therapeutic efficacy while reducing systemic toxicity to optimize treatment outcomes. The enzyme-cleavable and tumor-homing properties enable high enrichment of the payload in tumor tissues, generating a robust bystander effect that delivers favorable anti-tumor activity even in tumors with low or absent antigen expression.

In 2025, the phase I clinical trial results of YL201 in advanced solid tumors were published in Nature Medicine. Among 287 evaluable patients, the overall objective response rate (ORR) reached 40.8%, with a disease control rate (DCR) of 83.6%.

Specifically, in patients with extensive-stage small cell lung cancer (ES-SCLC), the ORR soared to 63.9%, significantly outperforming the current standard of care for later-line therapy (topotecan yields an ORR of approximately 24%). For nasopharyngeal carcinoma patients, the ORR hit 48.6%, also superior to existing treatments. Notably, the study is the first to report the efficacy of a B7H3-targeted agent in pulmonary lymphoepithelial carcinoma, with an ORR of 54.2%.

Currently, multiple clinical studies of YL201 are underway worldwide. Among them, the development of YL201 for SCLC and nasopharyngeal carcinoma indications has entered phase III clinical trials in China. Meanwhile, YL201 is actively undergoing a series of monotherapy and combination therapy trials to explore its therapeutic potential across various solid tumor types.

The advantages of YL201’s design are underscored by the development setbacks of its direct competitor, ifinatamab deruxtecan (I-DXd for short).

In late 2025, Daiichi Sankyo and Merck & Co. suspended patient enrollment in the global phase III clinical trial Ideate-Lung02 of I-DXd, citing a higher-than-expected incidence of grade 5 interstitial lung disease (ILD) events.

As reported by Xieyi Jun, the toxin used in I-DXd adopts the same successful design employed in Daiichi Sankyo’s HER2-targeted ADC (DS-8201), featuring a highly potent toxin. This toxin exhibits a strong bystander effect, enabling efficient elimination of tumor cells with low or heterogeneous antigen expression.

However, when applied to the B7H3 target, the high-dose administration strategy adopted to overcome limitations such as low target internalization efficiency significantly amplified the inherent risk of pulmonary toxicity.

Nevertheless, recent reports indicate that the U.S. Food and Drug Administration (FDA) has lifted certain clinical restrictions on I-DXd.

With the lifting of the restrictions, Daiichi Sankyo and Merck & Co. can resume the phase III clinical trial IDeate-Lung02 to evaluate the efficacy of I-DXd in treating recurrent SCLC. However, the trial remains on hold in the European Union, and Daiichi Sankyo and Merck & Co. will continue to engage in discussions with the European Medicines Agency (EMA) to seek the lifting of the suspension.

In 2001, B7H3 (CD276) was first identified as an immune checkpoint molecule belonging to the B7 family.

In non-malignant tissues, B7H3 primarily functions to suppress adaptive immunity by inhibiting the activation and proliferation of T cells. In malignant tissues, however, B7H3 inhibits tumor antigen-specific immune responses, thereby exerting a tumor-promoting effect. Additionally, B7H3 exhibits non-immune pro-tumor functions, including facilitating tumor cell migration and invasion, angiogenesis, chemoresistance, and epithelial-mesenchymal transition (EMT), as well as modulating tumor cell metabolism.

B7H3 is highly expressed in differentiated malignant cells and tumor-initiating cells with low heterogeneity, and it shows a high expression frequency across multiple cancer types (accounting for 60% of 25,000 tumor samples). In contrast, its expression level in normal tissues is relatively low. These characteristics have made B7H3 a research hotspot in the field of immunotherapy in recent years.

Currently, immunotherapeutic agents targeting B7H3 include monoclonal antibodies (mAbs), bispecific antibodies, antibody-drug conjugates (ADCs), and CAR-T cell therapies, among others.

Given that the B7H3 receptor has not yet been clearly identified, the development of B7H3 monoclonal antibodies faces considerable challenges. However, for ADCs, B7H3 represents an ideal target. Its characteristic of high expression in tumor tissues and low expression in normal tissues provides ADCs with precise "navigation" capability and a favorable therapeutic window, enabling them to act as highly efficient "biological missiles".

Data from the PharmSnap New Drug Intelligence Database shows that there are 70 B7H3 ADC candidates currently under research globally. The majority of these candidates remain in the early stages of development, with only a small number advancing to mature development phases.

According to incomplete statistics, four B7H3 ADCs have now entered Phase III clinical trials. In addition to the aforementioned YL201 and I-DXd, the pipeline also includes GSK’227/HS-20093 (a collaboration between Hansoh Pharmaceutical and GSK) and QLC5508 (a collaboration between Bright Horizon Therapeutics and Qilu Pharmaceutical). Among these late-stage clinical candidates, three originate from China. Once again, China has emerged as the undisputed leader in the global B7H3 ADC space.

Within the second-tier pipeline, China-developed B7H3 ADC candidates continue to dominate as the major driving force.

At the recently concluded J.P. Morgan Healthcare Conference (JPM), BioNTech highlighted key clinical data of its novel B7H3 ADC, BNT324/DB-1311, in prostate cancer.

In patients with metastatic castration-resistant prostate cancer (mCRPC) who had received multiple prior lines of therapy, BNT324/DB-1311 achieved an objective response rate (ORR) of 42.3%, a disease control rate (DCR) of 90.4%, a 6-month radiographic progression-free survival (rPFS) rate of 67.7%, and a 9-month rPFS rate of 58.0%.

In 2023, BioNTech entered into a licensing agreement with DualityBio, securing the overseas rights to a portfolio including the B7H3 ADC candidate DB-1311 and the HER2 ADC candidate DB-1303, with an upfront payment of $170 million and additional milestone payments of up to $1.5 billion.

BioNTech plans to initiate a pivotal Phase III clinical trial of BNT324/DB-1311 as a first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) in 2026, challenging the current standard of care to capture the early-stage market share.

Beyond single-target ADCs, bispecific antibody-drug conjugates (BsADCs) targeting B7H3 have emerged as a critical exploration direction for next-generation technologies.

On December 5, 2025, IDEAYA Biosciences announced that its candidate IDE034 had been granted investigational new drug (IND) approval by the U.S. Food and Drug Administration (FDA), making it the world’s first B7H3/PTK7 bispecific ADC to enter clinical development.

IDEAYA in-licensed IDE034 from Biocytogen in July 2024, in a deal valued at up to approximately $406.5 million in potential total consideration.

IDEAYA expects to commence patient enrollment in the first quarter of 2026, with a primary focus on evaluating the efficacy and safety of the drug in solid tumor types co-expressing B7H3 and PTK7, such as lung cancer, colorectal cancer, head and neck cancer, and ovarian/gynecological malignancies.

Domestic enterprises are also aggressively advancing their pipelines in the B7H3 bispecific ADC space.

Innovent Biologics’ IBI3001, the world’s first clinical-stage B7H3/EGFR bispecific ADC, was licensed to Takeda Pharmaceutical alongside two other ADC candidates in October 2025, in a deal worth up to $11.4 billion in total potential consideration—a record-breaking achievement for China’s innovative drug outbound licensing transactions.

Additionally, Innovol Lake’s ILB-3103 (a DLL3/B7H3-targeted agent) has completed preclinical efficacy validation; DualityBio’s DB-1419 (a PD-L1/B7H3 bispecific ADC) demonstrated stronger T-cell activation than PD-L1 monoclonal antibodies in preclinical studies, with in vivo antitumor efficacy superior to monotherapy and combination therapy regimens. It is currently undergoing Phase I/II clinical trials.

The potential of B7H3 extends far beyond antibody-drug conjugates (ADCs).

In the radiopharmaceutical space, B7H3 once came tantalizingly close to commercialization, only to face a disappointing setback at the final hurdle with the U.S. Food and Drug Administration (FDA).

In 2022, Y-mabs’ new drug application (NDA) for ¹³¹I-omburtamab—a B7H3-targeted radiopharmaceutical drug conjugate (RDC)—was rejected by the FDA. The regulatory agency cited insufficient evidence demonstrating that the drug could improve overall survival (OS) in pediatric patients with neuroblastoma and central nervous system/leptomeningeal metastases (CNS/LM).

Yet, this setback did not bring an end to the B7H3 RDC story.

In July 2025, Radiopharm’s Betabart (RV01) received FDA clearance to initiate clinical trials. This is a lutetium-177 (¹⁷⁷Lu)-labeled radiopharmaceutical, whose key design feature is its selective targeting of the 4Ig-B7H3 isoform. This isoform is the predominantly expressed variant in multiple solid tumors such as pancreatic cancer and neuroblastoma, enabling more precise tumor-targeted therapy.

Betabart’s Phase I clinical trial was launched in the second half of 2025, with preliminary clinical data expected to be released in the first half of 2026.

Meanwhile, B7H3 has emerged as a promising novel target for CAR-T cell therapies in overcoming solid tumors. Preclinical studies have shown that B7H3-targeted CAR-T therapies exhibit favorable specificity with a low risk of severe off-target effects, demonstrating significant therapeutic potential. In this cutting-edge field of research, Chinese companies have once again secured a leading position globally.

The most advanced B7H3 CAR-T candidate is MT027, an off-the-shelf universal CAR-T (UCAR-T) cell therapy developed by Maoxing Biotech. On December 22, 2025, the FDA granted approval for the initiation of its Phase II clinical trial for the treatment of recurrent glioblastoma multiforme (rGBM). Unlike the lentiviral or retroviral vectors commonly used in the industry, MT027 adopts a non-viral gene editing manufacturing process, further enhancing safety as well as the precision and controllability of production.

Domestically developed B7H3 CAR-T products that have entered clinical stages include TX103 from Tuoxin Tiancheng and TAA06 from Biosciences Gene.

Among these, the Phase I clinical trial of TX103 for recurrent and progressive grade 4 glioma obtained approval from the FDA in October 2023 and from China’s Center for Drug Evaluation (CDE) in January 2024, respectively. As for TAA06, which is indicated for the treatment of relapsed/refractory neuroblastoma, it was granted orphan drug designation by the FDA back in 2022 and received approval to initiate Phase I clinical trials in China in July of the same year.

In the PD-1 era, Chinese pharmaceutical companies mostly participated in global competition through a fast-follow strategy. Entering the IO 2.0 era, the landscape has fundamentally changed. In terms of R&D progress for multiple cutting-edge targets, Chinese enterprises have achieved collective leadership, emerging as an indispensable driving force in the global innovation landscape.

The competition around the B7H3 target has epitomized the historic transformation of China’s innovative drugs—from catching up and keeping pace to attempting to take the lead. Whether the first-mover advantage in R&D can ultimately be converted into discourse power in the global market will be the key to testing the success of this leap forward.