- Approach to Discovery
- Our Portfolio
- Phortress - CYP-activated , DNA-interactive agent (breast, ovarian, renal, lung)
- PMX 500 - Telomere targeting agents (broad spectrum activity)
- PMX 700 - repair resistant DNA-interactive agents (broad spectrum activity)
- PMX 900 - Base Excision Repair inhibitors, undisclosed target (broad spectrum activity)
- About Cancer
 |
||
 |
 |
 |
 |
||
PMX 700 Programme - repair resistant DNA-targeted anti-cancer agents (Broad spectrum activity)
The cytotoxic agent temozolomide (Temodar / Temodal), was originally discovered by Pharminox's Chief Scientific Officer Malcolm Stevens. This drug, now marketed by Merck & Co, Inc, has rapidly achieved blockbuster drug status and has beocme the gold standard treatment for glioblastoma multiforme, the most common form of brain cancer, when given concomitantly with radiotherapy and then as adjuvant therapy. It is also approved for use in patients with melanoma.
Temozolomide is most effective in a relatively small number of tumour types, because the majority of tumours have intracellular mechanisms that repair the DNA damage that it causes.
The ability to achieve long-term curative responses in patients with temozolomide-sensitive tumours is also compromised by the emergence of resistance. This is associated with the over-expression of methylguanine methyltransferase (MGMT), which is able to repair the O6 methylguanine adducts that are formed by temozolomide and that are central to its efficacy.
The Pharminox PMX 700 programme is a rational drug design programme to design, synthesise and develop compounds with similar properties to temozolomide, but which form adducts that cannot be repaired by MGMT. Pharminox believes that an agent with these properties would have the potential to be effective in a broader range of tumour types, including tumours with inherent or acquired resistance to temozolomide. We would also expect there to be a significant opportunity for combination use with other anti-cancer agents, in particular the new PARP (Poly (ADP Ribose) Polymerase) inhibitor class of DNA repair inhibitors, which are frequently used in combination with temozolomide and which have been shown to significantly potentiate its anti-tumour activity.
In vitro and in vivo proof of principle has already been established with the new Pharminox agents and further screening is ongoing with the most active compounds to identify a preferred candidate for IND-enabling studies.
