K-679 / Kowa - LARVOL DELTA

Ketone ester alleviates sepsis-associated liver injury through β-hydroxybutyrylation of STAT1. (PubMed, Immunobiology) - "KE also reduced hepatic M1 macrophage markers, IL-6 and IL-12 expression, and STAT1 Ser727 phosphorylation in LPS-treated wild-type mice, whereas these effects were attenuated by K679R. These results show that STAT1 K679 Kbhb contributes to the inhibition of macrophage M1 polarization by KE and is involved in its protective effect against LPS-induced liver injury."

IO biomarker • Journal • Hepatology • Infectious Disease • Inflammation • Liver Failure • Septic Shock • BAX • BCL2 • IL12A • IL6 • STAT1

Selective intratumoral distribution and post-T-DXd activity of K-679, an ultra-high-DAR EGFR-targeted antibody drug-loaded unimicelle conjugate (ADUC) (AACR 2026) - "We investigated whether the ADUC design of K-679 enables tumor-selective pharmacokinetics (PK), extensive intratumoral distribution, spatial pharmacodynamics, and activity following prior T-DXd treatment. K-679 versus a benchmark ADC (cetuximab‑DM1 ADC, cleavable disulfide linker, DAR ~4.5) was evaluated in head-to-head comparisons using EGFR-expressing CDX (HT-29, SK‑OV-3, SK-CO-1 [KRAS G13V]) evaluated at DM1-equivalent dosing. The ultra-high-DAR ADUC design of K-679 confers tumor-selective PK, extensive intratumoral distribution, concordant spatial pharmacodynamics, and activity after prior T-DXd. These data support clinical development for EGFR-expressing solid tumors with low/heterogeneous antigen density and post-T-DXd settings."

ADC • Oncology • Solid Tumor • CD31 • HER-2 • KRAS • PECAM1

K-679: A novel, ultra-high-DAR antibody drug-loaded unimicelle conjugate (ADUC) enabling more effective treatment in EGFR-expressing solid tumors compared to general ADCs (AACR 2025) - "Using this platform, we developed K-679, which combines cetuximab with DM1-loaded unimicelles. Antigen-binding specificity and cellular internalization of K-679 were evaluated using surface plasmon resonance, flow cytometry, and fluorescence microscopy. Our findings establish K-679 as a promising therapeutic candidate for heterogeneous EGFR-expressing solid tumors, characterized by a more potent anti-tumor effect through an exceptionally high DAR, enhanced drug accumulation into tumors and significant bystander effect."

ADC • Oncology • Solid Tumor • EGFR

K-679: A Novel Antibody Drug-loaded Unimicelle Conjugate Demonstrates Tumor-Selective Pharmacokinetics, Extensive Intratumoral Distribution and Superior Efficacy in Non-Clinical Animal Models (Canada Newswire) - "The compound, developed using Kowa's proprietary micelle technology, has demonstrated tumor-selective pharmacokinetics, extensive intratumoral distribution, and superior efficacy in EGFR-expressing solid tumors compared to conventional antibody drug conjugates (ADCs). The data will be presented at The American Association for Cancer Research (AACR) Annual Meeting 2026..."

Preclinical • Solid Tumor

Hepatocyte ApoJ accelerates injury-induced liver fibrosis by activation STAT3 through Ranbp2 mediated-SUMOylation. (PubMed, Cell Mol Gastroenterol Hepatol) - "ApoJ plays a pivotal role in accelerating the progression of liver fibrosis. Therapeutic strategies targeting the ApoJ/STAT3/RanBP2 axis may offer a novel approach for the prevention and treatment of fibrotic liver diseases."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • CLU • RANBP2 • STAT3 • TGFB1

K-679: A Novel Antibody Drug-loaded Unimicelle Conjugate with Ultra-High Drug Loading Capacity Demonstrates Superior Efficacy in EGFR-Expressing Solid Tumors (PRNewswire) - "Kowa Company...today announced an upcoming presentation of non-clinical data for K-679...The compound, developed using Kowa's proprietary micelle technology, has demonstrated superior efficacy in EGFR-expressing solid tumors compared to conventional antibody drug conjugates (ADCs). The data will be presented at The American Association for Cancer Research (AACR) Annual Meeting 2025, taking place April 25th-30th, 2025 in Chicago, Illinois."

Preclinical • Solid Tumor