Phylogica is advancing its internally-generated oncology candidates aimed at intracellular targets towards formal preclinical development.
Phylogica’s Intracellular Pipeline
The most progressed of these candidates are our proprietary Phylomer® iMyc payloads, combined with our FPP, aimed at the high-value intracellular cancer target Myc.
Myc is a transcription factor oncogene that is ‘activated’ in >50% of human cancers and is associated with poor clinical outcomes.
There is compelling evidence that direct inhibition of Myc can lead to complete eradication of existing tumours.
In experiments conducted by Dr Laura Soucek and Gerard Evan at UCSF, mice were genetically engineered to produce Myc-dependent lung cancers. When expression of a potent Myc inhibitor, ‘Omomyc’, was switched on in these animals, the established tumours were eradicated. Similar results have subsequently been observed with blood cancers such as leukaemia and lymphoma, as well as for liver, pancreatic, lung and brain cancers.
It is one of the most sought after targets in cancer but has proven elusive to direct inhibition with potent conventional small molecule therapies.
Highlights of Phylogica’s iMyc program include:
- Preliminary intravenous animal data using FPP-Omomyc suggesting evidence of efficacy in the EμMyc lymphoma model and the T11 basal breast cancer model.
- Multiple active hits identified against N-Myc and c-Myc.
- Hits modeled as rich in helices & structurally diverse (e.g. coiled-coil like).
- Primary iMyc hits before any sequence maturation can exhibit target binding affinities comparable to natural ligand (Max) and Omomyc protein.
- Some iMyc hits comparable or better than Omomyc in repression of reporter gene activity (Nanoluciferase) and in killing Myc-addicted cells.
- FPP-iMyc conjugates stable over hours in serum.
STAT5 and YB1 Programs
Our earlier-stage oncology candidates, the proprietary Phylomers aimed at the complementary STAT5 and YB1 intracellular targets in the Myc pathway, are initially being progressed with the support of external academic collaborations.