A selective Chk1 (checkpoint 1) inhibitor, V158411, is the lead molecule potentially indicated for the treatment of a broad range of cancers in combination with chemotherapy or radiotherapy as well as single agent therapy for a subset of cancers.
Vernalis is currently seeking a licensing partner, with a proven track record in the development and ideally also commercialisation of oncology products for the further advancement of our Chk1 inhibitor programme, including the lead compound V158411 and back-up candidate series with oral dosing potential.
V158411 successfully completed IND/CTA-enabling safety studies in 2012 and is ready to start Phase I studies in patients with advanced cancers.
Possible Clinical Indications of Chk1
Chk1 inhibition represents a novel therapeutic strategy to enhance the lethality of DNA-damaging chemotherapeutic drugs in p53 pathway defective cancers. Abrogation of the remaining intact cell cycle checkpoint should increase tumour cell death. Several Chk1 inhibitors have demonstrated potentiation of a range of cytotoxic chemotherapy drugs (i.e. gemcitabine, irinotecan and paclitaxel) both in vitro and in a wide range of in vivo pre-clinical models of cancers. This “synthetic lethality” approach should increase the therapeutic activity of the chemotherapeutic agent without increasing the systemic toxicity as normal cells should remain protected by their functional p53 pathway. Therefore, Chk1 inhibitors have the potential to be combined with a wide range of cytotoxic chemotherapeutic agents for the treatment of a diverse selection of human cancers.
In addition to acting as potentiators of cytotoxic chemotherapy, Chk1 inhibitors may also have clinical utility as single agents. Recent evidence suggests that Chk1 inhibitors may exhibit single agent anti-tumour activity in cancers with underlying defects in DNA repair, DNA damage response or DNA replication mechanisms. Sensitivity to single-agent Chk1 inhibitors has been demonstrated by Vernalis and others in several cancer types including neuroblastoma, Myc-driven lymphoma, triple negative breast cancer, ovarian cancer, leukemia and lymphoma cell lines of various origins.
Vernalis will seek a licensing partner with expertise and proven capabilities in the development and commercialisation in one or more of the indications where Chk1 has potential therapeutic applications.
To express an interest in discussing the potential licensing of this programme, please email email@example.com