As per the results, EG01257, a low nanomolar potent molecule, reduced the rate of tumour growth and showed no evidence of toxicity. NRP-1 is a therapeutic target of increasing interest for the treatment of cancer; consequently Ark intends to seek a partner to develop its NRP-1 programme further.
In the recent pre-clinical proof of principle study in a murine model of lung cancer, a single daily dose of EG01257 given for two weeks, was shown to reduce the rate of tumour growth by 52% (p=0.017). No evidence of toxicity was seen in the study, consistent with finding of earlier toxicity work at high doses.
NRP-1 is originally discovered as a Vascular Endothelial Growth Factor (VEGF) co-receptor, has been shown to have other potential therapeutic activity independent of VEGF, via a range of important growth factors such as PDGF and HGF. Because of the multiple pathways that NRP-1 can influence, tumours treated with NRP-1 antagonists are less likely to escape from treatment control which is a problem with anti VEGF drugs with more restricted modes of action.
Ark Therapeutics has synthesised a number of non cytotoxic NRP-1 small molecule antagonists in the low nanomolar potency range which have been designed by a unique combination of structural and mutational biology and computational chemistry in conjunction with scientists at University College London.
Ark Therapeutics said that antagonism of the NRP-1 receptor has shown a triple anticancer effect by directly impairing tumour cell growth, inhibiting the development of new blood vessels which ‘feed’ tumours’ (anti-angiogenic) and reducing cancer cell mobility (potentially anti-metastatic).
John Martin, chief scientific officer at Ark Therapeutics, said: “This result, from a single dose of EG01257, is extremely promising and compares very favourably with other approaches to block this receptor. Whilst we had much larger molecules where we had demonstrated the different anti-tumour effects, our success in creating small molecules potent in low nanomolar concentrations is a significant advance and we are delighted to report these results. Treatment of cancer through this new target offers great promise and is an important development for all cancer sufferers.”
Nigel Parker CEO of Ark Therapeutics, said: “We are very pleased with our transition to nanomolar potency small molecules; these first results are very encouraging and we look forward to conducting further trials alongside a suitable partner in due course.”