Pacylex is developing
- a predictive diagnostic test that identifies patient candidates for
- a small molecule inhibitor with high anticancer activity and low toxicity
- a proprietary new medicinal chemistry process with broad applicability
Pacylex has demonstrated
- PCLX-001 eradicates established tumours in three lymphoma or leukemia cell line xenograft studies
- PCLX-001 eradicates established drug-refractory aggressive lymphoma in a patient derived xenograft study
- PCLX-001 achieves tumour regression, comparable to standard-of-care treatment, in solid tumour xenograft studies
- Multiple common cancer types have the biomarker for drug sensitivity based on:
- RNA level data in cells from 19 types of cancer
- Protein level data in clinical samples from 11 types of cancer (survey ongoing)
- Our sensitivity biomarker test performs well in formalin-fixed paraffin-embedded clinical tumour samples, standard methodology in clinical pathology
- Our new synthetic pathway reduces the 13 step synthesis of PCLX-001 to 3 steps with high yield; this new proprietary medicinal chemistry is of broad applicability
Our first product is a precision medicine approach comprised of:
- A highly-sensitive, antibody-based diagnostic test that identifies the absence of N-Myristoyltransferase 2 (NMT2) in the tumours of cancer patients. The loss of NMT2 confers sensitivity to our lead drug and identifies a subset of patients for treatment.
- A highly specific drug, PCLX-001, that exploits the sensitivity of cancer cells deficient in NMT2. NMTs, our drug targets, are key enzymes involved in the regulation of cell signalling and represent a first-in-kind target in the battle with cancer.
What is myristoylation and NMT?
Protein myristoylation is an essential part of cellular signaling. It is the addition of a 14 carbon fatty acid that helps proteins interact with membranes for signaling.
It plays an overall pro-survival role and more than 200 proteins are myristoylated. The loss of myristoylation leads to loss of protein membrane targeting and signaling function.
There are two enzymes named N-myristoyltransferases (NMT1 and NMT2) that perform the myristoylation reaction in each cells.
We show that NMT2 expression is lost in numerous cancers. The prevalence of the loss is predicted to reach 70- 82% in certain blood cancers, namely leukemias and lymphomas.
This loss allows the specific killing of cancer cells by targeting the remaining NMT1 enzyme in cancer cells with our drug PCLX-001 (see figure below). This strategy spares normal cells because they have two NMTs.
We have focused our initial efforts towards the treatment of lymphomas, which account for 5% of cancers, with our secondary indications to follow.