A privately owned New Zealand biotech company has made huge progress in developing a replacement for the PSA prostate cancer test.
At present, there are 100 million PSA tests conducted worldwide each year but the test reliability suffers from false negative and false positive results with PSA testing costing global health systems around US$2 billion annually.
Caldera Ltd was established in 2010 as a molecular diagnostic development company. Prostate cancer is its first target, though the current development work has the potential, eventually, to target all cancers.
Breast cancer would be be the next target, says managing director Graham Watt.
The work is based on next generation sequencing (NGS) technology, which was developed for research purposes. Watt says NGS is beginning to migrate to diagnostic work.
“It's going to be a rapidly developing technology,” he says.
Caldera has a bank of around 40 gene biomarkers, which are screened to quantify and compare to those of the healthy population. To do that, the signal from the biomarker is first amplified.
After the biomarker signal is amplified, the samples are barcoded and sequenced. The resulting raw sequencing data is analysed and converted to count tables, which show the relative frequency of the biomarkers.
That is further analysed against known relationships in the literature and is presented in a visual format.
Chief scientist Dr Kristen Chalmet says the bench-top Illumina MiSeq NGS machine, which is purchased commercially, provides the basic software.
Caldera links that to its own in-house-developed software, which, again, is programmed mostly on the Unix platform.
A sequencing run typically contains a number of libraries, testing for selected biomarkers from a range of patients. A run might analyse two library samples from each of three patients, each testing for around 40 biomarkers, or one library from six patients.
“It's very computer-intensive,” Chalmet says. One specific run will produce 20Gb of data and typically, Caldera does three runs a week.
“We then have a huge challenge to put the data in a format that is clinically useful,” she says.
The company employs nine scientists in the laboratory - there are 40 shareholders, including a major hospital group, angel investors, and Stephen Tindall's K1W1 fund.
The company founder was prominent scientist Dr Jim Watson, who is no longer working day to day but remains as a science advisor.
Watt says large multinationals such as Roche are exploring adapting NGS technology to routine diagnostic testing, with Caldera in discussions with several of them.
“Commercially, we need to partner with a large diagnostic company,” he adds. “We see ourselves as generating the intellectual property.”
Watt was formerly managing director of Roche Diagnostics for Australia and regional head of Southeast Asia.
Currently, Caldera is in stage 2 of its development programme. Stage one was a clinical study to identify the genetic markers and build gene signatures.
Watt says he expects to be in full partner discussions by the fourth quarter this year.