DN015089 / Shanghai De Novo Pharmatech - LARVOL DELTA

Preclinical characterization of an anti–HER2-STING immune-stimulator antibody conjugate in HER2+ solid tumor (SITC 2024) - "Compared with intratumorally administration of DN015089, the expression of chemokines was prolonged, leading to better downstream T-cell activation. In CT-26 tumor bearing immunocompetent mice, treatment with DN028073 (1mg/kg) treatment alone achieved strong antitumor activity better than treatment with Enhertu ® (10mg/kg)...The activation of cGAS-STING signaling will probably contribute to tumor ICD and downstream lead to the recruitment of cytotoxic T cells (CTLs) to the tumor site. In conclusion, our study highlights the localized delivery of STING agonist to tumor may induce ICD and the immune-enhancing defense, which holds significant implications for future research and clinical applications."

IO biomarker • Preclinical • Oncology • Solid Tumor • CGAS • STING

Preclinical characterization of an anti–HER2-STING immune-stimulator antibody conjugate in HER2+ solid tumor (SITC 2024) - "Compared with intratumorally administration of DN015089, the expression of chemokines was prolonged, leading to better downstream T-cell activation. In CT-26 tumor bearing immunocompetent mice, treatment with DN028073 (1mg/kg) treatment alone achieved strong antitumor activity better than treatment with Enhertu ® (10mg/kg)...The activation of cGAS-STING signaling will probably contribute to tumor ICD and downstream lead to the recruitment of cytotoxic T cells (CTLs) to the tumor site. In conclusion, our study highlights the localized delivery of STING agonist to tumor may induce ICD and the immune-enhancing defense, which holds significant implications for future research and clinical applications."

IO biomarker • Preclinical • Oncology • Solid Tumor • CGAS • STING

Preclinical Characterization of an Anti–HER2-STING Immune-Stimulator Antibody Conjugate in HER2+ Solid Tumor (EACR 2024) - "Here we describe DN028073, designed to selectively deliver our currently phase 1 clinical drug DN015089 (CTR20212462) to HER2+ cells through ADC format...In CT-26 tumor bearing immunocompetent mice, treatment with DN028073 (1mg/kg) treatment alone achieved strong antitumor activity better than treatment with Enhertu ® (10mg/kg)...In pharmacokinetics and pharmacodynamics, DN028073 has a preferable PK profile and can activate immune system via in intravenous (i.v.) and subcutaneous (s.c.) administration.Conclusion Preclinical strong antitumor activity and favorable drug-like properties have motivated clinical testing of STING-ISAC for novel immunotherapies. The potential of other new target delivery and new combination therapies might provide new choice for locally advanced or metastatic solid tumors."

IO biomarker • Preclinical • Oncology • Solid Tumor • STING

Preclinical Characterization of an Anti–HER2-STING Immune-Stimulator Antibody Conjugate in HER2+ Solid Tumor (EACR 2024) - "Here we describe DN028073, designed to selectively deliver our currently phase 1 clinical drug DN015089 (CTR20212462) to HER2+ cells through ADC format...In CT-26 tumor bearing immunocompetent mice, treatment with DN028073 (1mg/kg) treatment alone achieved strong antitumor activity better than treatment with Enhertu ® (10mg/kg)...In pharmacokinetics and pharmacodynamics, DN028073 has a preferable PK profile and can activate immune system via in intravenous (i.v.) and subcutaneous (s.c.) administration.Conclusion Preclinical strong antitumor activity and favorable drug-like properties have motivated clinical testing of STING-ISAC for novel immunotherapies. The potential of other new target delivery and new combination therapies might provide new choice for locally advanced or metastatic solid tumors."

IO biomarker • Preclinical • Oncology • Solid Tumor • STING