KBD111 / Chengdu Baiyu Pharma - LARVOL DELTA

KBD111 is a highly selective, long-acting and brain-penetrant PARP1 inhibitor (AACR 2026) - "Background: Currently, several pan-PARP inhibitors such as olaparib, niraparib, and rucaparib are approved for the treatment of cancers with homologous recombination deficiency (HRD)...In addition, hematological toxicity was evaluated in vitro in CD34+ hematopoietic stem cells and in vivo in rats. KBD111 exhibited over 5,000-fold selectivity for PARP2 by DNA-trapping assays, demonstrated potent anti-proliferative activity against BRCA-mutant cancer cell lines, while showing markedly reduced cytotoxicity toward normal CD34⁺ hematopoietic stem cells (IC₅₀ >10,000 nM) compared to talazoparib (IC₅₀ = 27 nM)...Furthermore, KBD111 achieved superior tumor growth inhibition compared to AZD5305 in DLD-1 BRCA2⁻/⁻ xenograft models following once every two weeks oral dosing. In an intracranial MDA-MB-436-luc model, KBD111 also demonstrated enhanced efficacy relative to AZD9574 under QW oral dosing... KBD111 is a highly potent, long-acting and brain-penetrant PARP1 inhibitor with..."

Oncology • BRCA • BRCA2 • CD34 • HRD • PARP2

KBD111 is a highly selective, long-acting and brain-penetrant PARP1 inhibitor (ESMO 2025) - "Background Currently, several pan-PARP inhibitors such as olaparib, niraparib, and rucaparib are approved for the treatment of cancers with homologous recombination deficiency (HRD)...Results KBD111 exhibited over 5,000-fold selectivity for PARP2 by DNA-trapping assays, demonstrated potent anti-proliferative activity against BRCA-mutant cancer cell lines, while showing markedly reduced cytotoxicity toward normal CD34 + hematopoietic stem cells (IC 50 >10,000 nM) compared to talazoparib (IC 50 = 27 nM)...Furthermore, KBD111 achieved superior tumor growth inhibition compared to AZD5305 in DLD-1 BRCA2 - / - xenograft models following once-weekly oral dosing. In an intracranial MDA-MB-436-luc model, KBD111 also demonstrated enhanced efficacy relative to AZD9574 under QW oral dosing...A phase 1 trial is planned for 2026. Legal entity responsible for the study The authors."

Oncology • BRCA • BRCA2 • CD34 • HRD • PARP2