Public Funding for Hox Therapeutics Limited

Homeobox or 'HOX' genes are an important family of genes encoding HOX proteins that control cell and tissue growth in the embryo. After birth, these genes are normally silenced, however, they can be re-activated in tumours in which they have a role in promoting cancer cell proliferation and survival. Importantly, in cancer, these genes are not mutated but overexpressed or 'switched on' and act through partnership with other proteins to drive cancer proliferation. Our novel drug is a small peptide which stops HOX proteins binding to their key partner protein, PBX, resulting in rapid cancer cell death. Our agent, HTL-001, has been tested in cancer cells representative of 14 different malignancies, in human cancer tissue in the 'test tube' as well as in animals. It has consistently demonstrated selective toxicity for cancer ells, sparing normal cells/tissue. A study of increasing doses of HTL-001 given once to rats and rabbits has already demonstrated that HTL-001 is safe and not toxic. The second study proposed here will test the safety of multiple doses of HTL-001 in animals since this is in line with how the drug would be used in human clinical trials. If successful, this is a vital scientific and compulsory regulatory step would allow us to define the starting dose of HTL-001 for human trials which could commence in December 2018\. There is an urgent unmet need for new cancer therapies with novel mechanisms of action as current treatments for advanced disease are largely palliative. We have shown HOX gene dysregulation is very common in most cancers, and a rational target for new treatments. We have recently shown that HTL-001 doubles the survival in mice which have been seeded with glioma (brain cancer). This development is very promising and the results are at least as good if not significantly better than other drugs tested at this stage - particulary as we are optimistic that HTL-001 will be well tolerated. Although not as common as many cancers, around 11,500 patients are diagnosed with brain cancer in the UK very year, of which only about 40% survive after one year. It is a condition of very high unmet medical need and this project, which will ensure that our drug is safe for patients' use in a clinical trial, has the potential to be of major benefit to patients - in brain cancer initially and hopefully in other cancers in the longer term.