Date: 2012-11-05
Type of information: Grant
Company: Pharminox (UK)
Investors: Biomedical Catalyst Fund (UK)
Amount: £0.5 million (€0.6 million)
Funding type: grant
Planned used: The proceeds of the grant will be used to accelerate progress on the Company’s PMX 700 programme, which is aimed at developing new treatments for glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. In most major countries, the current standard treatment for GBM involves the use of the chemotherapy agent temozolomide (Temodar™, Temodal™, Merck & Co., Inc.) in conjunction with radiotherapy. However it is known that a significant proportion of GBM patients respond poorly to temozolomide treatment due to inherent or acquired resistance caused by a DNA repair mechanism, which is able to overcome temozolomide-induced DNA damage. The aim of the Pharminox PMX 700 programme is to design and develop improved follow up compounds to temozolomide that overcome this repair mechanism, thereby offering a new treatment option for those GBM patients for whom the use of temozolomide is ineffective.
Others: Pharminox , the UK-based cancer drug discovery and development company, announced that it has received notification from the Technology Strategy Board that it has been offered a grant of just under £0.5 million under the UK Government’s £180 million Biomedical Catalyst funding initiative for research and development in the life sciences. Receipt of the grant is conditional on a review by the Technology Strategy Board and agreement of terms between both parties. The award was announced by Technology Strategy Board and is one of 32 projects awarded funding totalling £39 million. These are the first substantial awards made from the £ 180 million Biomedical Catalyst programme managed by the Technology Strategy Board and the Medical Research Council.
Temozolomide (TMZ) is an approved drug which has rapidly become the “standard of care” for the first-line treatment of glioblastoma multiforme (GBM) when given concomitantly with radiotherapy and then as adjuvant therapy. The focus of the Pharminox PMX 700 programme is to design and develop agents that overcome a key limitation of TMZ, namely the repair of TMZ-induced DNA damage by the DNA damage repair protein methylguanine-DNA methyl transferase (MGMT). High expression of MGMT is associated with inherent and acquired resistance to TMZ treatment, which limits effective therapy in a significant proportion of GBM patients, and also restricts TMZ’s utility to a very small number of other tumour types. This program seeks to provide a new treatment option for TMZ-resistant GBM patients by designing agents that form a TMZ-like DNA lesion which is incapable of being processed by MGMT, thereby overcoming resistance without inhibiting the DNA repair protein, which is also required by normal cells.
The Pharminox team has made significant progress in designing and synthesising compounds that meet the key programme criteria. Over 400 novel compounds have now been designed and synthesised, and evaluated in a detailed in vitro screening cascade. A substantial body of structure-activity relationship data has been generated and further optimisation work is ongoing. The next stage, which is the subject of the BioMedical Catalyst grant announced, will be to profile the most promising compounds emerging from the screening cascade in in vivo studies in TMZ–sensitive and TMZ-resistant GBM and other cancer models, with the objective of establishing preclinical proof of concept and selecting a preclinical development candidate to go forward into IND-enabling studies.
Pharminox is building a broad patent estate around the PMX 700 programme encompassing composition of matter, method of use and process claims. Three separate patent applications have now been filed in the United States, the PCT countries and other major markets covering composition of matter and field of use claims, the first of which has already achieved its first grant, in South Africa. A fourth patent application has been filed covering a novel and more environmentally friendly route of synthesis for TMZ itself that will also be applicable to many of the new Pharminox compounds.
Therapeutic area: Cancer - Oncology
