SNV-001 / Synnovation Therap - LARVOL DELTA

Activity of PARP1-selective inhibitor SNV-001 in models of HRD cancers as monotherapy and in combination (AACR 2024) - "SNV-001 showed greater efficacy at lower doses compared to olaparib at 100 mg/kg or at equivalent doses of AZD9574...SNV-001 enhanced cytotoxicity of the DNA-damaging agent topotecan or carboplatin in Capan-1 (BRCA2mut) and HCC1395 (BRCA1mut) cells. Synergy was seen between SNV-001 and cell cycle check point inhibitors camonsertib (ATRi) or adavosertib (WEE1i) in DLD1 (BRCA2 -/-) and UWB1.289 (BRCA1mut) cells, as DNA damage induced by PARP1 trapping relies on cell cycle modulation for repair. Combination of SNV-001 with polymerase theta inhibitor ART558 or USP1 inhibitor KSQ4279 exhibited synergistic effects in DLD1 (BRCA2 -/-) or UWB1.289 (BRCA1mut) cells...Current data highlight a potential strategy for improving treatment efficacy and overcoming resistance. Further clinical investigations are warranted to validate this combination strategy."

Monotherapy • Oncology • BRCA1 • BRCA2 • HRD • PARP2 • USP1

Discovery of a potent and selective PARP1 inhibitor and trapper with anti-tumor activities in HRD tumors (AACR 2023) - "Furthermore, SNV-001 showed dose-dependent tumor growth inhibition using low daily doses with greater efficacy compared to olaparib dosed at 100 mg/kg once daily. In the cohort receiving a higher dose of SNV-001, all animals showed complete regression after 35 days of treatment without any clinical signs of toxicity.In summary, we have discovered SNV-001, a potent and selective PARP1 inhibitor and trapper that shows excellent activity against cancer models with HRD in vitro and in vivo. These data support advancement of SNV-001 into clinical development for patients with tumors characterized by HRD."

Oncology • Ovarian Cancer • Pancreatic Cancer • BRCA • BRCA1 • BRCA2 • HRD • PARP2