Breakthrough HER2 ADC: DB-1303/BNT323 Outperforms Kadcyla in Positive Phase III Results in China
DB-1303 (BNT323) achieved a positive Phase III readout in HER2-positive breast cancer, reinforcing DualityBio’s ADC platform and BioNTech’s oncology expansion beyond immunotherapy. The trial shows potential for global commercialization, including a planned China BLA filing.
BioNTech and Duality Biologics announced that their pivotal Phase III trial (NCT06265428) of DB-1303 (BNT323, trastuzumab-pamirtecan) in HER2-positive unresectable or metastatic breast cancer met its primary endpoint of progression-free survival (PFS) at a pre-specified interim analysis.
The study, conducted in China, compared DB-1303 directly against trastuzumab emtansine (Kadcyla, T-DM1) in patients previously treated with trastuzumab and taxane-based chemotherapy. This is the first positive Phase III readout from the BioNTech–Duality collaboration initiated in 2023, validating their strategy to advance antibody-drug conjugates (ADCs) for solid tumors.
Discovery & Collaboration Origins
DB-1303 was discovered and developed by Duality Biologics, leveraging its proprietary dual-payload ADC platform. The molecule combines a trastuzumab-derived HER2-targeting antibody with a novel topoisomerase-I inhibitor payload attached via a cleavable linker optimized for stability and tumor-selective release.
In April 2023, Duality entered into a strategic global partnership with BioNTech, which acquired ex-China commercial rights (outside Mainland China, Hong Kong, and Macau). The deal covered DB-1303 and DB-1311 (B7-H3 ADC), underscoring BioNTech’s diversification into oncology ADCs beyond immunotherapy. DB-1303 is now one of the first late-stage assets in BioNTech’s ADC pipeline, with Duality retaining responsibility for discovery and development leadership.
Duality’s 2025 IPO: A Strong Market Endorsement
Duality successfully listed on the Hong Kong Stock Exchange (ticker: 9606.HK) in April 2025, raising approximately HK$1.64 billion (≈ US$211 million) through an offering priced at HK$94.60 per share. On its debut day, the stock surged ~117%, peaking at HK$205 per share — the strongest first-day return among biotech IPOs on HKEX since 2021.
The IPO attracted 115x retail oversubscriptions and 13.5x institutional demand, including a US$65 million investment from cornerstone investors such as BioNTech. Nearly 45% of the proceeds was earmarked for advancing DB-1303 and DB-1311, underscoring their strategic centrality to Duality’s pipeline.
Development & Regulatory Status
- Mechanism: DB-1303 is a third-generation HER2 ADC carrying a topoisomerase-I payload with a cleavable linker, designed for potent tumor killing and reduced off-target toxicity.
- Breakthroughs: The drug has shown antitumor activity in both HER2-positive and HER2-low tumors, and in 2023 received FDA Breakthrough Therapy and Fast Track designations for advanced endometrial cancer (NCT05150691).
- Ongoing Trials: The global DYNASTY-Breast02 trial (NCT06018337) is evaluating DB-1303 in HR-positive, HER2-low metastatic breast cancer after hormone and/or CDK4/6 inhibitor progression.
- Regulatory Plans: DualityBio intends to file a BLA submission in China based on NCT06265428, while BioNTech is evaluating regulatory pathways in the U.S. and EU.
Competitive Landscape
The HER2-targeted ADC market is led by Enhertu (trastuzumab deruxtecan, AZ/Daiichi Sankyo), which transformed treatment for HER2-positive and HER2-low breast cancer. Roche’s Kadcyla (T-DM1) remains a widely used second-line standard of care. DB-1303’s differentiators include:
- A different topoisomerase-I payload with a potentially favorable safety profile, particularly lower rates of interstitial lung disease compared with Enhertu.
- Broad activity across HER2-positive, HER2-low, and endometrial cancers, positioning it for expansion beyond breast cancer.
- A head-to-head win vs. T-DM1 in China, a clinically meaningful advance over the current second-line standard of care.
Comparison of HER2-Targeted ADCs
| Drug (Company) | Target | Payload / Linker | Key Indications (Phase III) | Trial Comparator | Regulatory Status |
|---|---|---|---|---|---|
| DB-1303 / BNT323 (DualityBio / BioNTech) | HER2 | Topoisomerase-I inhibitor (cleavable linker) | HER2-positive MBC (post-trastuzumab + taxane, vs T-DM1) | T-DM1 (Kadcyla) | Phase III (China) positive; Breakthrough Therapy (endometrial cancer); BLA to NMPA planned |
| Enhertu (trastuzumab deruxtecan) (AZ / Daiichi Sankyo) | HER2 | Topoisomerase-I inhibitor (deruxtecan, cleavable linker) | HER2-positive & HER2-low breast cancer (various settings) | Physician’s choice chemo / T-DM1 | Approved globally (breast, gastric, NSCLC); >$3B annual sales |
| T-DM1 (Kadcyla) (Roche / Genentech) | HER2 | DM1 (maytansine derivative, non-cleavable linker) | HER2-positive breast cancer (2L, post-trastuzumab + taxane) | vs lapatinib + capecitabine (EMILIA) | Approved globally, but being displaced by Enhertu and now challenged by DB-1303 |
Outlook & Implications
- Regulatory filings: NMPA submission is planned, with global filings contingent on confirmatory data.
- Commercial strategy: DualityBio holds commercialization rights in Mainland China, Hong Kong, and Macau, while BioNTech retains rights elsewhere.
- Pipeline leverage: Success with DB-1303 strengthens Duality’s ADC platform, which also includes DB-1311 (B7-H3), DB-1310 (HER3), DB-1305 (TROP2), and DB-1419 (bispecific ADC).
What It Means for China
Breast cancer is the second most common malignancy among Chinese women (~350,000 new cases annually). With limited Enhertu access due to cost and NRDL constraints, DB-1303 could provide a more accessible, locally driven alternative. Its success underscores China’s growing ability to deliver globally competitive, first-in-class oncology innovation.
Sources
- BioNTech and DualityBio Press Release: BioNTech and DualityBio Announce Phase 3 Trial of ADC Candidate. Sep 5, 2025
- DualityBio Website:en.dualitybiologics.com
- ClinicalTrials.gov: NCT06265428, NCT06018337, NCT05150691