Skip to content

#ADC/偶联药物

Today 0 items
Oct 15Thu
  1. biorxiv.org42

    Spatial Tumour Tissue Distribution Dynamics of a Bicycle Peptide-MMAE Toxin Conjugate Profiled by Targeted Mass Spectrometry

    Laser capture microdissection coupled to targeted LC-PRM mass spectrometry maps the spatial distribution of MMAE released from the NECTIN-4-binding Bicycle Drug Conjugate zelenectide pevedotin (BT8009) at sub-tissue resolution in mice. The method showed progressive accumulation and sustained retention of MMAE in tumour tissues over 24 h, while levels in plasma, liver and muscle declined after early exposure, and revealed heterogeneous MMAE distribution between tumour cell-rich and stroma-rich regions with distinct temporal patterns.

Oct 13Tue
  1. biorxiv.org51

    Trastuzumab deruxtecan kills skin and uveal melanoma in vivo by HER2-independent payload release

    Trastuzumab deruxtecan (T-DXd) inhibited all subcutaneous melanoma PDXs and outperformed trastuzumab emtansine (T-DM1), which had limited activity, while liver models were less sensitive. Parental and ERBB2-knockout xenografts responded similarly at first, though knockout tumors regrew earlier, and melanoma cells resisted both ADCs in vitro with little trastuzumab uptake. Tumor-derived cathepsin L found outside melanoma cells suggests payload release can occur extracellularly, independent of HER2.

    Why it matters: Suggests T-DXd may work in melanoma through HER2-independent payload cleavage, widening its potential use beyond HER2-positive tumors.

Oct 10Sat
  1. biorxiv.org58

    NECTIN4 defines a subtype-dependent tumor state coupling enfortumab vedotin targetability to antitumor immunity in bladder cancer

    NECTIN4, the target of enfortumab vedotin (EV), acts as a subtype-dependent determinant of tumor state and antitumor immunity in bladder cancer. Integrating clinical multi-omics, spatial and single-cell immune profiling, and experimental models, the work shows NECTIN4-high basal/squamous muscle-invasive tumors had favorable survival, higher checkpoint inhibitor response rates, and a CD8+ T cell-inflamed microenvironment, with no comparable associations in luminal papillary tumors; NECTIN4-low models were preferentially sensitive to HDAC inhibition.

Oct 8Thu
  1. N Engl J Med40

    Advances in Systemic Treatment of Breast Cancer.

    A New England Journal of Medicine review traces systemic therapy for breast cancer since 2020, covering targeted therapies, antibody-drug conjugates and immunotherapy across biologic subtypes. CDK4/6 inhibitors remain foundational in hormone-receptor-positive, HER2-negative disease, trastuzumab deruxtecan is reshaping HER2-positive treatment, and immune checkpoint inhibitors have improved outcomes in triple-negative breast cancer. Unresolved issues include treatment sequencing, predictive biomarkers, circulating tumor DNA analysis and equitable access to high-cost therapies.

Oct 2Fri
  1. biorxiv.org59

    KRAS inhibition drives adaptive surfaceome remodeling and reveals ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer

    Quantitative temporal profiling of the global, phosphorylation, and surface proteome in PDAC shows that KRAS inhibition upregulates the cell surface protein ALPP through compensatory JAK2/STAT3 signaling. The authors developed a clinical-grade ALPP/ALPPL2-targeting antibody drug conjugate with site-specific MMAE conjugation, which showed single-agent efficacy in PDAC models and enhanced internalization and anti-tumor efficacy combined with KRAS inhibitors, pointing to a combination strategy to forestall KRASi resistance.

    Why it matters: It defines the KRASi-induced proteome and links a surface target to a clinical-grade ADC combination strategy against resistance.

  2. biorxiv.org52

    KRASG12C Inhibition Remodels the Non-Small Cell Lung Cancer Surfaceome to Uncover Targetable Vulnerabilities

    KRAS G12C inhibitors remodel the cell surface proteome of KRAS G12C-mutant lung adenocarcinoma, and folate receptor alpha (FOLR1) emerges as a therapeutically actionable target that is significantly upregulated during treatment, part of an acute cellular state transition toward epithelial identity. Quantitative temporal proteomic profiling across cell lines, tumor models, and treatment durations identified this adaptation. Combining KRASi with mirvetuximab soravtansine-gynx, a clinically approved FOLR1-targeting antibody drug conjugate, enhanced tumor cell cytotoxicity and deepened response and tumor control in cellular and in vivo models.

Oct 1Thu
  1. BioCentury59

    I-DXd withdrawal thins October PDUFA calendar

    Merck & Co. and Daiichi Sankyo withdrew their BLA for ifinatamab deruxtecan two weeks before its PDUFA date; the partners had sought accelerated approval for extensive-stage small cell lung cancer in patients whose disease progressed on platinum chemotherapy. The withdrawal leaves at least five FDA decisions on the PDUFA calendar for October. The article does not state what the companies plan to do next with the programme.

    Why it matters: A BLA withdrawal by Merck and Daiichi Sankyo cuts October's expected FDA decision count to five.

Sep 30Wed
  1. biospace.com50

    Merck, Daiichi Sankyo retract accelerated approval request for lung cancer ADC

    Merck and Daiichi Sankyo have voluntarily withdrawn their accelerated approval application for the antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer after platinum-based chemotherapy, after the FDA said the data did not satisfy requirements for the proposed indication. The application rested on a 48.2% confirmed objective response rate from the Phase 2 IDeate-Lung01 study. A Phase 3 trial in ES-SCLC with enrollment nearing completion continues and could support a future filing.

    Why it matters: Voluntary withdrawal of an accelerated approval application narrows the regulatory path for a key Merck-Daiichi Sankyo ADC.

Sep 28Mon
  1. biopharmadive.com56

    Merck, Daiichi end plans to seek speedy approval of lung cancer ADC

    Merck & Co. and Daiichi Sankyo withdrew their U.S. application for accelerated approval of ifinatamab deruxtecan, or I-DXd, in extensive-stage small-cell lung cancer after the FDA indicated Phase 2 response rate data were insufficient; a decision had been expected by Oct. 10. The B7-H3-targeting drug is still being tested against chemotherapy in relapsed disease, a trial in which recruitment was temporarily halted last year after higher than anticipated deaths from a serious lung condition. Competing B7-H3 drugs licensed to GSK (riz-rez) and Roche (tam-peli) have advanced, and I-DXd is also in Phase 3 testing in prostate cancer and esophageal squamous cell carcinoma.

    Why it matters: A rejected accelerated approval reshapes the B7-H3 race in small-cell lung cancer among Merck, GSK and Roche.

Sep 17Thu
  1. STAT News57

    STAT+: England to cover AstraZeneca breast cancer drug, a result of U.K.-U.S. drug pricing deal

    English health authorities agreed to provide AstraZeneca's Enhertu through the NHS for women with metastatic breast cancer whose tumors have low levels of HER2, ending a years-long dispute. The decision extends the antibody-drug conjugate to an estimated 1,000 people in England and follows a U.S.-U.K. drug pricing deal under which a U.K. health agency raised cost-effectiveness thresholds. Scotland has covered the drug since 2023, as have 26 other European countries.

Sep 9Wed
  1. biocentury.com60

    GSK takes rights to Hutchmed’s KRAS-antibody conjugate: Deals Report

    GSK plc is paying $110 million up front for most global rights to HMPL-A830, a dual-targeted oncology therapy from Hutchmed China that links a KRAS inhibitor payload to an anti-EGFR antibody. HMPL-A830 is the first deal from Hutchmed's Antibody-Targeted Therapy Conjugate (ATTC) platform, which has also produced two PI3K-payload programs now in Phase I testing. The same report also covers Alteogen's delivery-tech deal with Novartis and Menarini's local in-licensing of Gan & Lee's obesity program.

    Why it matters: First licensing deal from Hutchmed's ATTC platform gives GSK most global rights to a KRAS-antibody conjugate.

Sep 3Thu
  1. fiercebiotech.com64

    GSK pens $1.3B Hutchmed deal for early-stage KRAS-EGFR cancer asset

    GSK has licensed Hutchmed's preclinical KRAS-EGFR antibody conjugate HMPL-A830, paying $110 million upfront in a deal worth up to $1.295 billion, excluding Mainland China, Hong Kong, Macau and Taiwan. The candidate delivers a KRAS inhibitor to EGFR-expressing tumors and is slated to enter trials later this year, initially in colorectal, pancreatic and lung cancer. Hutchmed will run Phase 1 trials, after which GSK takes over R&D and commercialization outside select Asian territories.

    Why it matters: GSK is paying up to $1.295 billion for a preclinical first-in-class KRAS-EGFR candidate, a notable early-stage oncology licensing deal.

Sep 2Wed
  1. Nature64

    Modular in vivo antibody-ADC click to reverse drug resistance in tumours.

    Sequentially administered antibodies and ADCs bearing trans-cyclooctene and tetrazine moieties ligate in vivo to form functional antibody-ADC click constructs, removing the dependence on a single target antigen. In preclinical models of HER2 and EGFR co-expression, including tumours with low, ultralow, negative or heterogeneous HER2 expression and tumours resistant to or ineligible for conventional HER2-directed ADCs, the approach showed improved antitumour activity over standard ADC monotherapy and over antibody plus ADC combinations. The platform requires no extensive antibody re-engineering and extends to other receptor pairs.

    Why it matters: It offers a modular route to overcoming antigen-heterogeneity-driven resistance to antibody-drug conjugates without antibody re-engineering.

Aug 31Mon
  1. Nature73

    A binding-to-release strategy for targeted anticancer drug delivery.

    A binding-to-release strategy decouples payload release from receptor endocytosis by placing an electrophile cleaved by a nucleophilic residue in the target binding pocket, implemented through phosphorus(V)-phenol exchange chemistry. A FAP-targeted SMDC built this way achieved 5.9-fold higher tumour MMAE exposure (AUC0-120 h) than an internalization-dependent FAP-SMDC, tumour-to-blood ratios 14.7- and 3.6-fold higher than FAP-ITR-SMDC and FAP-ITR-ADC, tumour-to-liver ratios 55.1- and 58.7-fold higher, and near-complete tumour regression across tumour models. The approach also extended to PD-L1 and an mRNA-display-derived FAP peptide, broadening the target scope for conjugates.

    Why it matters: It removes the endocytosis requirement that limits drug conjugates to roughly 10% of targets.

Aug 28Fri
  1. fiercebiotech.com57

    Genentech doubles down on ADC-resistant cancers with $1B DualityBio pact

    Roche's Genentech is paying DualityBio $45 million upfront for rights to antibody-drug conjugates built on the Chinese biotech's Dupac platform, with the deal worth more than $1 billion in potential milestones. DualityBio will generate and develop ADCs that deliver Dupac payloads, designed to retain efficacy in tumors that progress on topoisomerase-based ADCs such as Enhertu and Trodelvy, to Genentech-picked targets, with Genentech taking sole responsibility for development after phase 1a. BioNTech, GSK and BeiGene struck earlier deals for DualityBio ADCs in 2023 and 2024.

    Why it matters: A $1 billion licensing deal targeting patients who progress on approved ADCs addresses a growing unmet clinical need.

Aug 24Mon
  1. fiercepharma.com47

    Daiichi Sankyo promotes Ken Keller to lead new commercialization unit

    Daiichi Sankyo has promoted Ken Keller, who has led its global oncology business for five years, to chief commercialization officer of a new globally integrated commercialization unit starting April 1. The restructured organization covers five regions, with internal appointments including Yuichi Yomasu in China, Markus Kosch in Europe, Marcelo Goncalves in Latin America, Kenji Shigeta in North America and Nobuo Murakami in Japan, Asia and the Pacific. The unit supports Daiichi Sankyo's plan to become a top-five oncology company by 2035 and to make five drugs available in 20 new indications by 2030.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org