Under the agreement Horizon will test Cylene’s CK2 inhibitor against a panel of X-MAN cell-lines which harbour key mutant genes that drive cancer including, K-Ras, B-Raf, PTEN, P13K, EGFR, and B-catenin, selected to represent defined patient populations.
The cell-lines will be tested under various in vitro assay conditions designed to mimic the tumour environment, then used to pinpoint the patients who will respond best to CX-4945. Cylene meanwhile will perform assays in-house, focussing on drug combinations with standard chemotherapies and novel targeted agents.
Dr. Darrin Disley, executive chairman at Horizon Discovery, said the preclinical models will “more accurately reflect the disease in defined patient populations,” and will identify patients “most likely to respond well in clinical trials, aiding the design of more rational, faster and cheaper clinical trials.”
He told Outsourcing-Pharma that each X-MAN cell-line has a cancer mutation, introduced using Horizon’s GENESIS gene editing technology. He said each line comes with its equivalent normal, or ‘isogenic,’ cell-line allowing comparative assessment of the drug candidates’ effect.
Based on these findings, Disley continued, “the most responsive mutant lines will inform us which patients carry the same mutation, and therefore should be recruited into a focused Phase I clinical trial.”
Added to this, Cylene will be able to use X-MAN cell-lines with combined mutations to examine drug sensitivity in patient’s tumours which are “genetically complex, and carry more than one mutant cancer gene that drives their uncontrolled expansion.”
Preclinical patient identification to cut trial costs
Horizon claims this collaborationist approach will make drug therapeutics research cheaper and make regulatory approval more rapid.
“Enabling smaller, more focussed trials will bring large cost savings and most importantly, lead to less drug failures,” saidDisley who believes this is “a major component of cost that is threatening the current ‘one-size-fits-all’ healthcare paradigm.”
Biotech companies struggle to “position their drug for partnering with pharma, or secure the funds needed to perform a clinical trial of their own,” said Disley. “This is very expensive, and pharma companies are no longer prepared to fund multiple clinical trials that may see 40 per cent or more of its patients subsequently excluded based upon genetic factors,” he added.
Disley says over 60 pharma companies are already using X-MAN technology to triage potential in-house compounds, and believes “all biotech and pharma companies will follow this route now as current drugs don’t work and future drugs have a lot of promise. Cancer drug development is therefore a huge unmet need.”
He hopes “personalised medicine will continue to become a reality,” adding “It’s time to get the right drug into the right patient.”