01 Domestic B7H3 ADC: From Clinical Data to Market Ambitions
In 2024, the global ADC landscape is set to reach a turning point amidst the celebration of DS-8201 breaking the $10 billion expectation, with the B7H3 target emerging as a dark horse and becoming the next storm center.
Taking domestic products as an example, although it has seemingly formed a “double breakout” trend, the differentiation is also quite prominent. Yilian Biotech’s YL201 has shown an ORR of 63.9% and a DCR of 91.7% in the phase 1b data published in Nature Medicine for extensive-stage small cell lung cancer (ES-SCLC), surpassing the traditional chemotherapy ORR level of 20-40%; its ORR for nasopharyngeal carcinoma even reached 54.2%, demonstrating broad cancer type potential. Hansoh Pharmaceutical’s HS-20093 achieved ORRs of 61.3% and 17.4% in ES-SCLC and osteosarcoma, respectively, constructing a moat with a dual-line approach of “lung cancer + sarcoma”.
In contrast, globally, Daiichi Sankyo’s I-DXd holds benchmark significance. Daiichi Sankyo/MSD’s I-DXd has initiated four global phase 3 clinical trials covering major indications such as small cell lung cancer and prostate cancer. Its phase 2 data for ES-SCLC shows a median overall survival (mOS) of 11.8 months for the 12 mg/kg group, significantly improving over the 6 months of traditional chemotherapy. Frost & Sullivan predicts that the B7H3 ADC market will reach $300 million by 2027 and explode to $5.5 billion by 2032, with a compound annual growth rate of 74.2%.
Of course, while the market outlook is promising, the heated BD transactions also reveal some underlying concerns.
In 2023, there were over five global B7H3 ADC transactions, with Hansoh Pharmaceutical’s $1.71 billion agreement with GSK and the joint development case between Yiming Biotech and BioNTech confirming the target’s popularity. However, the lesson from Shiyao’s EO-3021, which faced overseas returns due to differences in clinical data between China and the US (ORR 22.2% vs 47.1%), warns that efficacy is the hard currency for internationalization.
02 Survival Rules Amidst the ADC Downturn: From False Prosperity to Hardcore Innovation
In 2024, the outbound amount in the ADC field has plummeted by 43% year-on-year, with star projects like Rongchang Biotech and Kelun BoTai facing returns or impairments, ringing alarm bells for the industry and exposing deep-seated crises under homogeneous competition. On one hand, there is a serious phenomenon of target clustering, with over 50% of domestic pipelines concentrated on five major targets such as HER2 and TROP2, which account for more than 75% globally.
On the other hand, technical shortcomings are highlighted, with insufficient iteration of linker-toxin platforms. Compared to Daiichi Sankyo’s DXd technology, which has been refined over 20 years, the domestic “micro-innovation” model is difficult to sustain. Additionally, there are risks in the business model, such as Shiyao’s Claudin18.2 ADC, which has a mere 2.3% upfront payment and a high milestone overseas model, placing the main R&D risks on domestic pharmaceutical companies.
In the face of such dilemmas, the ADC industry needs to seek breakthroughs through dual drives of platform innovation and clinical insights. Technically, breakthroughs are needed, such as Yilian Biotech’s TMALIN tripeptide linker, which overcomes traditional endocytosis limitations, and Yiming Biotech’s DB-1311 achieving a 28% ORR in metastatic castration-resistant prostate cancer (mCRPC), closely following Daiichi Sankyo’s I-DXd’s 25.4%, showcasing Best-in-class potential.
In terms of models, innovation is required. HengRui Medicine adopts a “NewCo model” to bind overseas resources, while BeiGene builds an international team to promote the global sales of Zebutini, actively exploring the leap from license-out to independent commercialization.
03 The Future Battle: Three Key Factors for B7H3 ADC Success
The current field of cancer treatment is undergoing a paradigm shift centered around ADCs (antibody-drug conjugates), with breakthrough progress mainly reflected in three dimensions:
Clinical validation of first-line treatment replacing chemotherapy. The combination of DS-8201 and pertuzumab has shown significant advantages in first-line treatment of HER2-positive breast cancer, with PFS data surpassing traditional platinum-containing chemotherapy regimens (e.g., THP regimen mPFS 19.1 months, expected to exceed 23 months for the DS-8201 combination), setting a benchmark for ADC frontline applications.
This successful path is being replicated in the B7H3 ADC field: Phase 3 clinical trials for YL201 and HS-20093 targeting ES-SCLC have been initiated, and if they continue to leverage their early data advantages (YL201 showing an ORR of 63.9% and mPFS of 6.3 months in the ES-SCLC subgroup), they are expected to overturn the existing platinum-containing chemotherapy standards.
Innovations in the synergistic effects of combination therapies. Combination therapy has become a key strategy for expanding indications, with Yiming Biotech’s DB-1311 and PD-L1/VEGF dual antibodies being the first global Ib/II phase clinical trial, pioneering a new paradigm of “B7H3 ADC + immune dual antibodies”.
This model draws on Gilead’s Trodelvy combined with Keytruda’s successful experience in triple-negative breast cancer (PFS significantly better than chemotherapy + PD-1 control group), achieving enhanced efficacy through complementary mechanisms. It is worth noting that combination schemes need to balance efficacy and safety; for instance, while the combination of DS-8201 and pertuzumab improves ORR, the incidence of grade ≥3 adverse events increases by 10%.
Global layout and commercial competition. Multinational pharmaceutical companies are accelerating their lead, such as Daiichi Sankyo’s I-DXd initiating a global phase 3 trial with 1440 cases in the mCRPC field (based on early mPFS of 5.3 months and mOS of 13 months data).
Domestic pharmaceutical companies need to overcome the data shortfall in European and American populations. If Hansoh Pharmaceutical’s cooperation model with GSK can be successfully replicated in the B7H3 field, it will help position the market. Currently, the global competition for B7H3 ADC has become intense, with molecules like I-DXd, YL201, and DB-1311 having differentiated advantages in efficacy and safety (e.g., DB-1311 showing a uORR of 28% in CRPC and a 6-month rPFS rate of 94.7%), which will determine the future market landscape.
This wave of transformation marks a leap in cancer treatment from traditional chemotherapy to precise targeting and combination therapies, with the core driving force being the reshaping of clinical pathways through the “high efficiency and low toxicity” characteristics of ADCs, while accelerating the iteration of treatment paradigms through global clinical layouts.
In summary, the ADC industry is undergoing a painful period of transition from capital bubbles to value return. The rise of the B7H3 target is not only a litmus test for the advancement of domestic innovative drug technology but also a pressure test for globalization capabilities. Only by breaking the shackles of homogenization through platform innovation and facing international competition with clinical differentiation can one break through in this $10 billion competition.