Daiichi Sankyo Discontinues Claudin-6 ADC DS-9606 Following Strategic Portfolio Review
核心洞察
Daiichi Sankyo has discontinued development of DS-9606, a claudin-6 (搜索)-directed antibody-drug conjugate carrying a modified pyrrolobenzodiazepine payload, following a strategic portfolio review.
The decision marks the first discontinuation of an anti-claudin-6 (搜索) ADC project, despite the company validating DS-9606's utility in germ cell tumors (搜索).
DS-9606 demonstrated a 15% overall response rate in phase 1 trials, which appeared uncompetitive compared to Torl Therapeutics (搜索)' ixotatug vedotin (搜索) showing 33% ORR in claudin-6 (搜索)-positive tumors.
Daiichi Sankyo has terminated development of its next-generation antibody-drug conjugate DS-9606, marking the first discontinuation of an anti-claudin-6 (搜索) ADC project and representing a significant setback for the Japanese pharmaceutical company's expansion beyond its successful deruxtecan platform.
The decision was announced during the company's third-quarter 2025 earnings call, where R&D chief Yuki Abe stated, "We've decided to discontinue its in-house development following a strategic portfolio review." The move comes despite the company having validated DS-9606's utility in germ cell tumors (搜索).
Clinical Performance and Competitive Landscape
DS-9606 demonstrated a 15% overall response rate in phase 1 trials, a figure that appeared uncompetitive in the evolving claudin-6 (搜索) targeting landscape. In contrast, Torl Therapeutics (搜索)' ixotatug vedotin (搜索), now positioned as the industry's most advanced anti-claudin-6 ADC, has shown a 33% overall response rate in mostly claudin-6-positive tumors. Notably, DS-9606's study did not require claudin-6-positivity for patient enrollment, potentially contributing to the lower response rate.
The discontinuation follows a pattern of challenges in claudin-6 (搜索) targeting across the industry. BioNTech previously stepped back from work in claudin-6, terminating one trial of the CAR-T therapy BNT211 and reporting disappointing results with the mRNA-encoded T-cell engager BNT142.
Technology Platform Implications
DS-9606 was designed as a claudin-6 (搜索)-directed antibody-drug conjugate carrying Daiichi Sankyo's modified pyrrolobenzodiazepine (mPBD) payload, a cancer-killing chemical that binds to and disrupts tumor cell DNA. The asset was intended to be the first in a planned series of ADCs carrying mPBDs, representing the company's effort to diversify beyond its high-profile deruxtecan payload used in drugs like Enhertu and Datroway.
Despite the discontinuation, Abe emphasized during the earnings call that the company has confirmed the usefulness of the mPBD platform and that "clinical programs will continue," exploring other targets and carrier antibodies. However, the pyrrolobenzodiazepine-based payload doesn't appear to be utilized in any other current Daiichi ADCs.
Strategic Context
Abe acknowledged that while there is "room for making more development" in the germ cell tumor area where DS-9606 showed utility, the company decided against continuing in-house development "given the portfolio perspective." This suggests the discontinuation reflects broader strategic priorities rather than solely clinical performance concerns.
The decision comes amid ongoing challenges for Daiichi Sankyo's ADC portfolio. The company has also delayed the readout from the Phase III Avanzar study testing its breast cancer (搜索) ADC Datroway in combination with AstraZeneca's PD-L1 blocker Imfinzi for first-line non-small cell lung cancer (搜索), pushing the timeline from the latter half of 2025 to the second half of this year.
Datroway has faced multiple setbacks, including a failed late-stage NSCLC study in May 2024 where it was unable to significantly boost overall survival versus docetaxel, and a subsequent Phase III failure in breast cancer (搜索) patients in September 2024.