When MSD and Daiichi-Sankyo's B7H3 ADC became the world’s first to submit an application for marketing authorization, a target once considered a "graveyard of R&D" is being collectively pushed by Chinese pharmaceutical companies to the brink of an explosion.
On April 13, Merck and Daiichi Sankyo jointly announced that the BLA for ifinatamab deruxtecan (I-DXd) had been granted Priority Review by the FDA, with a PDUFA date of October 10, 2026, becoming the world's first B7-H3 ADC drug to be submitted for marketing.B7H3 was once labeled as a "research graveyard" due to repeated failures in development, until the breakthrough in ADC technology reactivated this target. From barrenness to the "eve of explosion" in commercialization,Among more than twenty B7H3 ADCs currently in the global clinical stage, nearly 80% of the pipelines are surprisingly backed by Chinese pharmaceutical companies.From Hansoh, Yilian, Ying'en to Minghui, five B7H3 ADCs have advanced to Phase III clinical trials globally, with four originating from China.Behind China's innovative drugs stand multinational giants such as Roche, GSK, and BioNTech.China's indigenous innovation power and global MNCs are jointly launching an "alliance to encircle" Merck/Daiichi Sankyo on the next generation of blockbuster targets.How Did B7H3 Go from "Lady Macbeth" to "Sweetheart"? In This Race for a Multi-Billion Market of the Future, Who Will Cross the Finish Line First? Will the Safety Concerns Hanging Overhead Become the Second Shoe to Drop?B7H3 Reaches a "Historic Moment"Ifinatamab deruxtecan (I-DXd) is not only the world's first B7-H3 ADC drug to be submitted for marketing approval, but also the fourth ADC from Daiichi-Sankyo to enter the submission phase for marketing approval, following Enhertu, Dato-DXd, and HER3-DXd.The data foundation for submission to the market comes from the Phase II IDeate-Lung01 study. The results showed that among 137 patients treated with a 12mg/kg dose, the independently centrally reviewed confirmed objective response rate (ORR) reached 48.2%, the disease control rate (DCR) was 87.6%, and the median overall survival (OS) was 10.3 months. In the subgroup of patients who had previously received first-line treatment, the ORR was as high as 56.3%, with the median OS extended to 12.0 months.In an exploratory analysis of 65 patients with baseline brain metastases, the intracranial ORR reached 46.2%, demonstrating potential control effects on brain metastases lesions. In terms of safety, the incidence rate of treatment-related adverse events of grade 3 or higher was 36.5%, mainly including neutropenia, lymphopenia, and anemia.Despite B7H3's current dominance in the ADC field, it has also emerged from the "graveyard of research and development."As a member of the B7 ligand family, the B7H3 target was first discovered in 2001. In tumor biology, B7H3 can both suppress T-cell activity to assist in tumor immune escape and promote the migration, invasion, angiogenesis, and chemotherapy resistance of tumor cells.More crucially, B7H3 exhibits the typical characteristic of "high expression in tumors and low expression in normal tissues." Its expression rate is as high as 80% in non-small cell lung cancer (NSCLC) and reaches 65%-75% in small cell lung cancer (SCLC). It also shows abnormally high expression in various solid tumors such as esophageal cancer, prostate cancer, and breast cancer. This feature makes it an ideal "navigator" for targeted drugs.However,The early research and development around B7H3 was almost a "collective failure."At that time, the research and development strategies for B7H3 mainly focused on monoclonal antibodies (mAbs) and bispecific antibodies, attempting to activate the immune system by blocking the immunosuppressive effects of B7H3. However, the natural receptor of B7H3 has not been clearly identified, making it difficult for mAb drugs to take effect by blocking pathways like PD-1.The clinical failure that sent B7H3 into the doldrums came from the pioneer in the field: Denmark's Y-mAbs. Its radiopharmaceutical conjugate 131I-omburtamab, which falls under the RDC category, was once considered the most promising candidate to lead the B7H3 race, butIn 2022, the FDA Oncologic Drugs Advisory Committee (ODAC) voted 16:0 against it, questioning its inability to significantly improve overall patient survival, leading to the project's ultimate failure.The emergence of ADC technology has completely transformed the fate of B7H3. Simply put, there is no need to decipher the complex signaling pathways behind it; just use B7H3 as a navigational coordinate to deliver highly potent toxins precisely into tumor cells for targeted destruction. In October 2023, after Daiichi-Sankyo and Merck reached a collaboration involving three ADCs (including I-DXd) with a total value of up to $22 billion, global enthusiasm for the development of B7H3 ADC was ignited.Chinese Players "Join Forces to Surround and Annihilate"This ADC golden target, regarded as "the next TROP 2," is currently being primarily advanced in clinical research worldwide, yet the main drivers are concentrated in China.According to statistics from the PatSnap New Drug Database,Globally, no B7H3 ADC has been approved for marketing. Among over 60 related drugs under research, 24 are in clinical stages, with approximately 80% led by Chinese companies. Including ifinatamab deruxtecan (I-DXd), a total of five products worldwide have entered Phase III clinical trials.Since 2026, domestically produced B7H3 ADC has already seen two BD deals.First, Yilian Biotechnology announced an exclusive licensing collaboration with Roche on the B7H3 ADC drug YL201. Both parties will jointly advance the development and commercialization of this B7H3-targeted ADC across multiple solid tumor indications. Yilian Biotechnology will receive an upfront payment of $570 million along with near-term milestone payments. YL201 is currently under clinical investigation globally for various solid tumors and has been granted several Breakthrough Therapy designations by the FDA, including for the treatment of small cell lung cancer, nasopharyngeal carcinoma, and esophageal squamous cell carcinoma.Shortly thereafter, within less than 10 days, another Chinese pharmaceutical company, Innolake Biologics, announced an agreement with the UK's Ellipses Pharma Limited. Ellipses Pharma has obtained the development rights for Innolake’s ILB-3101 outside of Greater China. ILB-3101 uses Eribulin as its payload and can overcome resistance to topoisomerase I-based ADCs. Currently, Innolake is conducting Phase I clinical trials for ILB-3101 in China, while Ellipses will initiate Phase I clinical trials in the United States.Two deals have once again put B7H3 ADC in the spotlight.If the timeline is extended,Since 2023, MNCs such as GSK and BioNTech have been "sweeping up" B7H3 ADCs from Chinese pharmaceutical companies with real investments, forming a "group going overseas."Earlier than the collaboration between Merck and Daiichi Sankyo,BioNTech Partners with DualityBio for Licensing Collaboration, with $170 Million Upfront and Over $1.5 Billion in Additional Milestone Payments, introducing the overseas rights of B7H3 ADC drug DB-1311 (BNT324) and HER2 ADC drug DB-1303. According to the latest disclosed R&D progress, in late January 2026, BioNTech announced the initiation of a Phase III clinical trial for BNT324 as a first-line treatment for prostate cancer.Less than two months after Merck's collaboration with Daiichi Sankyo, by the end of 2023,GSK Secures Overseas Rights to HS-20093 from Hansoh with $185 Million Upfront and up to $1.525 Billion in Milestone PaymentsHansoh's HS-20093 is a fully humanized B7H3 ADC and is the fastest-progressing among Chinese pharmaceutical companies. It has received six Breakthrough Therapy/Priority Drug designations from regulatory authorities in China, the US, and Europe, covering multiple indications including non-squamous non-small cell lung cancer, ES-SCLC, and osteosarcoma.In addition to reaching cooperation with MNCs, BD transactions have also occurred between domestic pharmaceutical companies in China.May 2025,Minghui Pharmaceuticals has licensed the Greater China rights of MHB088C (QLC5508) to Qilu Pharmaceuticals for a total amount of 1.345 billion yuan (including a 280 million yuan upfront payment).As the fourth B7H3 ADC globally to enter Phase III, QLC5508 has adopted a differentiated toxin approach. Its payload, SuperTopoiTM, is 5-10 times more potent than DXd and has demonstrated exceptionally high tumor-killing activity in esophageal squamous cell carcinoma (ESCC) and mCRPC.In addition, several Chinese companies such as Kinsay and Mabwell are also advancing their B7H3 ADC pipelines. Mabwell's 7MW3711 has been approved for clinical trials in both China and the U.S. and has received FDA Orphan Drug Designation. Kinsay Pharma's dual-target B7-H3/PSMA bispecific antibody-drug conjugate (ADC) has also been approved for clinical trials.However, despite the frequent BD deals and the gradual emergence of commercialization prospects, the safety risks of B7H3 ADC cannot be ignored, as ILD (interstitial lung disease) remains the Sword of Damocles hanging overhead.Even Ifinatamab deruxtecan (I-DXd), recently submitted for marketing approval by Merck/Daiichi Sankyo, had a global Phase III clinical trial halted by the end of 2025 due to a higher-than-expected incidence of Grade 5 ILD events.In December 2025, due to the incidence of Grade 5 interstitial lung disease (ILD) events being higher than expected in the IDeate-Lung02 Phase III clinical trial, Daiichi-Sankyo voluntarily paused recruitment and enrollment in the global I-DXd clinical trials.Although the FDA partially lifted the clinical hold more than a month later after implementing additional safety measures, the trial remains on hold for recruitment in the EU to this day.As one of the most common severe adverse reactions of ADC drugs, drug-related ILD presents with diverse and non-specific clinical manifestations, which can be easily confused with tumor progression in the lungs or infections. This leads to a high risk of misdiagnosis or missed diagnosis. In severe cases, it may cause respiratory failure or even death in patients, making it a key focus for regulatory agencies such as the FDA.The influencing factors in the competition for B7H3 ADC are not only about efficacy, but also about safety and differentiated design. How to balance the potency of the toxin with patient protection is a "life-and-death gate" that all players must cross.Among the five B7H3 ADCs globally entering Phase III, Chinese pharmaceutical companies account for four spots, which is inseparable from the establishment of differentiated technology platforms. Yilian Biotech's TMALIN platform, Minghui Pharma's SuperTopoi™ payload platform, etc.,All have innovated in linkers, payloads, or mechanisms of action to balance efficacy and safety, avoiding the risk of ILD associated with early Dxd payloads.As I-DXd approaches its market launch, the window of opportunity for B7H3, which has moved from the "graveyard of R&D" to the "eve of an explosion," is rapidly narrowing. According to Frost & Sullivan's forecast,The first B7H3 ADC is expected to be approved in 2027, with the global market size reaching approximately US$300 million that year. By 2032, it will soar to US$5.5 billion, with an annual compound growth rate as high as 74.2%.MSD and Daiichi-Sankyo Have Seized the Commercialization Initiative; Can Roche, GSK, BioNTech, and Their Chinese Partners Form an Encircling Momentum?Second Review | Li Fangchen
Third Review | Li Jingzhi
