Dual androgen receptor programme
In 2020, using in-house expertise at the University of Surrey, the team identified a new opportunity in the field of prostate cancer, specifically the treatment of metastatic castrate-resistant prostate cancer (mCRMP).
First-in-class drug for castration-resistant prostate cancer
Prostate cancer affects around one million men worldwide and for those where cancer has proliferated beyond the prostate gland, the standard therapy is androgen deprivation and androgen receptor blockade.
It has been shown that androgen, produced primarily from the testes, drives prostate cancer through the androgen receptors. However, a small percentage of patients, and eventually almost all patients, become resistant to both hormone deprivation and drugs that block the androgen receptors.
This resistance is due to the emergence of AR variants which have lost the ligand binding site targeted by current androgen receptor antagonists. HOX is developing a new dual inhibitor of the androgen receptor which blocks both the binding site targeted by current drugs and a second site that also drives cancer.
Early development work on our dual androgen receptor inhibitor is extremely encouraging and we are currently in the process of preparing a development programme to deliver a lead molecule to the clinic.
HOX dual androgen receptor development programme represents an opportunity to address a market with considerable unmet medical needs and one served by drugs with annual sales in excess of $5 billion.
It also offers a relatively straightforward, small molecule, development pathway with a clear target patient population and is benchmarked against the current standard of care.
HOX’s current strategy in prostate cancer is to prioritise the development of its dual androgen receptor programme using internal resources.
HTL-003 is a novel, first-in-class androgen receptor inhibitor that not only inhibits conventional ligand binding domain (LBD), but also represses previously non-targetable major driver amino-terminus domain (NTD) of AR, and thus shows superiority over currently used AR inhibitors.
Currently approved androgen receptor (AR)-targeted drugs for prostate cancer inhibit AR signalling by blocking the activation of the AR ligand-binding domain (LBD). Castration-resistant prostate cancer (CRPC) frequently develops, sometimes driven by LBD-deficient AR variants (AR-Vs) that promote tumour growth through the amino-terminus transactivation domain (NTD).