NEW YORK (GenomeWeb) – Proteome Sciences said this week that it has signed a $2 million contract with Genting TauRx Diagnostic Centre, an affiliate of TauRx Therapeutics, to provide protein biomarker work in support of the company's Phase III trial of its Alzheimer's drug LMTX.
Proteome Sciences will analyze blood samples from patients enrolled in the trial and from age-matched controls with the aim of building protein panels for the detection of Alzheimer's and for monitoring treatment efficacy.
Under the terms of the deal, Proteome Sciences will receive $2 million in research fees comprising upfront and milestone payments, while GTD will receive a license to the company's existing blood biomarkers for Alzheimer's. The firms will share commercialization rights to any diagnostic assays developed.
The deal offers Proteome Sciences a chance to further validate its Alzheimer's biomarker discovery work in an actual drug trial cohort for the disease, Chief Operating Officer Ian Pike told ProteoMonitor.
Alzheimer's has been a significant area of focus for the company, as it has developed biomarker assays for the disease in both cerebrospinal fluid and plasma and is exploring casein kinase 1 delta inhibition as a potential therapy for the disease.
While the CSF biomarkers amyloid-β and tau are currently the most widely used protein markers in Alzheimer's diagnostics and clinical trial work, Pike noted, plasma markers are highly desirable as these can be measured without requiring patients to submit to a lumbar puncture.
This summer, Proteome Sciences researchers along with collaborators at King's College London published a paper in Alzheimer's & Dementia detailing a panel of 10 plasma proteins that appeared useful in predicting patients likely to progress from mild cognitive impairment to Alzheimer's disease.
The company also offers a panel of nine plasma proteins for Alzheimer's research including patient stratification in clinical trials.
In its work with GTD, Proteome Sciences aims to validate these collections of Alzheimer's plasma biomarker candidates in the clinical trial cohort while at the same time looking for additional novel markers, Pike said.
"It's a program to take all of our existing biomarker candidates and ... do a targeted measurement of those proteins [while] also adding the ability to discover new ones using a mixture of data-independent and data-dependent acquisition mass spec," he said.
The companies plan to look at around 1,000 patient samples, with Proteome Sciences applying its TMT CalibratorIV workflow, which, Pike noted, allows researchers to combine in the same run targeted analysis with a limited amount of discovery work.
Essentially, the method uses historical mass spec data combined with predictions from in silico tryptic digests to identify the best flying peptides for all the proteins a project aims to measure. Researchers can then build mass spec inclusion lists for those peptides and set the machine to survey those targets.
Then, with whatever measurement time is left over, the instrument will perform data-dependent analysis on whatever are the most abundant ions present at the time.
"So it's a good way of both covering everything you want to look at but still having a way to cover other [novel] things," Pike said, adding that this discovery element will be key to identifying markers for tracking patient response to GTD's LMTX therapy. Proteome Sciences plans to use a Thermo Fisher Scientific Orbitrap Velos Pro for the work, he said.
According to GTD, LMTX targets the tau pathway and is aimed at patients with mild to moderately severe Alzheimer's.
As Pike noted, thus far a major challenge in identifying biomarkers for treatment efficacy in Alzheimer's has been the failure of most drug trials for the disease to, in fact, show efficacy.
"The big problem is that there are very few cohorts where drugs have been successfully applied in Alzheimer's, so finding cohorts with reasonable efficacy in the first place is a challenge," he said.
He added that the project will be a chance for Proteome Sciences to explore "how you build the optimal panels within a disease where you already have good discovery data."
"I think the outcomes will be very valuable for shaping the best way of [building] these diagnostic and prognostic therapeutic monitoring-type assays," he said.
Proteome Sciences plans to begin its analysis this year and expects to be able to run the roughly 1,000 patient samples in around six months, Pike said. The timeline for data analysis and test development will depend on the progress of the clinical trial, though, he noted.
"The diagnostic we can get on with, but until we know the outcomes of the treatment arm we won't be able to do all the work on the treatment monitoring arm of the study," he said, estimating that in all the project would take between 18 months and two years.
In addition to the deal announced this week with GTD, Proteome Sciences continues to work on further validation of its Alzheimer's plasma markers through its collaboration with KCL.
The collaborators are working to line up additional patient samples to test the markers in larger cohorts and have identified several thousand samples they hope to use. Additionally, the two parties aim to move the 10 markers identified in the A&D study to a single diagnostics platform optimized for the test.
Proteome Sciences and KCL share intellectual property to the panel, with Proteome Sciences being in charge of its commercialization.