MecRx is a drug discovery company committed to developing drugs for targets that have so far proven to be undruggable.
MecRx is an early stage drug development company working on new treatments for cancer and novel mechanism of action antibiotics. Using proprietary “hit identification” technology, MecRx is developing inhibitors of cMyc, a protein that is deregulated in over 50% of all human cancers. MecRx draws on the expertise of the Peter MacCallum Cancer Centre and CSIRO and is headquartered in Melbourne, Australia.
Mutation and deregulation of the cMyc oncogene contributes to the formation and maintenance of many human cancers. Tumours with elevated levels of cMyc often exhibit highly proliferative, aggressive phenotypes and are often associated with resistance to primary treatments. Over 30 years of extensive study worldwide has convincingly shown that cMyc is a compelling target for therapeutic intervention. However, despite considerable efforts, no drugs that directly target cMyc have yet been developed.
MecRx is identifying and developing small molecule drugs for highly validated but historically hard to hit targets. Using MecRx proprietary technology the company has identified hits for cMyc, KRas2B and other valuable targets.
MecRx was founded in 2013 by an ex-pharma/biotech team. MecRx is run as a virtual company based in Melbourne, Australia and its shareholders and service providers include the Peter MacCallum Cancer Institute and CSIRO. The company secured $5m Series A investment from the MRCF (www.mrcf.com.au) and CSIRO in 2015.
The MYC gene encodes a nuclear transcription factor, which serves as a “master regulator" or “universal amplifier” of cellular metabolism and proliferation, controlling the expression of up to 15% of all human genes. Under normal physiological conditions, cMyc is dependent on mitogenic stimulation for its expression and function. cMyc activation during mitosis drives numerous processes required for cell division including up-regulation of protein synthesis and energy production, whilst at the same time inhibiting expression of genes with anti-proliferative functions.
cMyc expression is deregulated in the majority of human cancers including those of the cervix, breast, prostate, colon, lung, bladder, pancreas, brain, stomach and in melanoma. MYC gene mutations are rare and deregulated cMyc activity usually results from up-stream mutations affecting other oncogenes or tumour suppressors. cMyc activity is therefore required for the development and maintenance of the majority of tumour types, even when initiated by upstream signals.
cMyc is one of the most highly amplified oncogenes in many human cancers. It has been estimated cMyc overexpression contributes directly to the cause of up to 40% of cancers and it is often associated with resistance to first line therapies and a more aggressive phenotype. In tumours induced by cMyc up-regulation in transgenic mice, even brief cMyc de-activation triggers tumour regression accompanied by growth arrest, differentiation, and collapse of the tumour vascular system.
Atypically for a novel oncology target, multiple groups have provided extensive validation for the biological roll of cMyc inhibition in the treatment of cancer. Studies employing anti-sense DNA oligonucleotides, anti-sense mRNA, Triple-Helix Forming Oligonucleotides, Quadruplex-Forming Oligonucleotides, RNA interference strategies and synthetic peptide approaches have all provided compelling evidence that inhibiting cMyc activity is beneficial in a diverse range of pre-clinical cancer models.
As cMyc acts downstream of mitogenic signalling, inhibiting cMyc function would be effective irrespective of the oncogenic driver. There is therefore significant potential for combination therapies involving cMyc inhibitors and targeted inhibition of upstream driving lesions. Importantly, limited cell resistance mechanisms are available to circumvent cMyc inhibition and thus targeting cMyc offers a considerable advantage over existing targeted therapies.