NEW YORK(GenomeWeb) – Diagnostics firm Biodesix said this week that it is collaborating with Swiss proteomics firm Biognosys on companion diagnostic development.
The collaboration will use Biognosys' HRM mass spec technology to complement Biodesix's traditional MALDI-TOF approach to biomarker discovery and development, Paul Beresford, Biodesix's chief business officer, told GenomeWeb.
Specifically, the company aims to better understand the specific analytes underlying the MALDI-TOF mass spec signal comprising its tests, Beresford said.
While most protein and proteomic diagnostics rely on quantification of specific, known proteins, Biodesix has taken a different approach, instead evaluating patient samples by comparing patterns of MALDI mass spectra without actually quantifying, or, in some cases, even knowing the identity of the proteins underlying these spectra.
The company has had success with this approach, garnering companion diagnostics projects and launching and commercializing its MALDI-based Veristrat test for identifying likely responders to certain lung cancer therapies. However, Beresford said, it has found in the course of its companion diagnostics work that many of its pharma partners would like to better understand the proteins underlying the MALDI signatures generated by the company.
"Most pharma companies have a keen interest in the biology of how their drugs work and what patient populations work with their drug," he said. "So there was an interest in further understanding our MALDI-TOF signatures in terms of what are the underlying proteins or peptides that are over- or under-expressed within those signatures."
The effort also plays into the partnership announced last year between Biodesix and drug developer Aveo Oncology.
Under their agreement, the two parties are co-developing and commercializing Aveo's non-small cell lung cancer antibody drug ficlatuzumab and Biodesix's Veristrat as a companion test to predict best responders. The deal calls for Biodesix to fund the first $15 million of the drug development effort with the expenses thereafter split evenly between the two firms and profits from commercialization of the drug also split evenly.
Additionally, Biodesix is responsible for taking Veristrat through US Food and Drug Administration clearance or approval, which will likely require nailing down the specific proteins underlying the test's MALDI signature.
"The initial foundation of our collaboration [with Biognosys] was to understand the Veristrat signature in more detail in preparation for our engagement with the FDA," Beresford said.
The Biognosys agreement does not represent a shift away from Biodesix's MALDI-based discovery strategy, though, Beresford said. The company has "had a very exciting few months in terms of our MALDI-TOF discovery," he added, citing in particular its work on developing tests for assessing the effectiveness of cancer immunotherapies.
"We see it in terms of, we have a very good [MALDI] technology to rapidly discover tests and take them to market," he said. "At the same time, there is this market need for looking into the underlying biology. So it's not necessarily that we will use the Biognosys platform to go all the way to market. It's more, at this juncture, to help understand the biology behind the signatures."
Beresford did note, though, that if the HRM analysis determines that a MALDI-particular signature could be boiled down to a small number of proteins, Biodesix would consider moving that test to a more targeted platform like multiple-reaction monitoring mass spec or ELISA.
"The two approaches are very complimentary to each other," Stephan van Sint Fiet, Biognosys' chief commercial officer, told GenomeWeb. "With Biodesix's MALDI platform they are able to find a mass spec fingerprint that then allows them to stratify patient groups to distinguish between responders and non-responders. But the fingerprint is not telling you about the biology you are looking at — it is a hypothesis-independent method.
"Whereas, Biognosys is really identifying and quantifying total proteomes and basically saying, these are the proteins that are responsible for the difference between these two populations," he added. "So that is a hypothesis-driven approach, and it's relevant because if you are interested in further expanding on using those biomarkers or further validating them, then you benefit from knowing the biology behind them."
Biodesix's decision to collaborate with Biognosys on such analyses represents a vote of confidence by the company in that firm's data-independent acquisition HRM mass spec method.
In conventional shotgun mass spec, or data-dependent acquisition mass spec, the instrument performs an initial scan of precursor ions entering the instrument and selects a sampling of those ions for fragmentation and generation of MS/MS spectra. Because instruments can't scan quickly enough to acquire all the precursors entering at a given moment, many ions — particularly low-abundance ions — are never selected for MS/MS fragmentation and so are not detected.
In DIA, on the other hand, the mass spec selects broad m/z windows and fragments all precursors in that window, allowing the machine to collect MS/MS spectra on all ions in a sample.
Because DIA collects MS/MS spectra on all samples, it can provide more reproducible quantitative data than DDA methods, making it good for looking at changes in protein expression across many different samples, for instance. The trade-off is that DIA analysis typically doesn't identify as many proteins as DDA approaches.
The popularity of DIA approaches has grown rapidly in recent years, but it is still far less commonly used than traditional shotgun methods. Indeed, according to Biognosys, they are the only company that offers commercial DIA services.
Founded in 2008 as a spinout from the lab of Swiss Federal Institute of Technology Zurich researcher Ruedi Aebersold, Biognosys specializes in targeted mass spec approaches including MRM-MS and DIA (which, though it analyzes proteins on the proteome level, is essentially a targeted method).
The company has to date largely focused on sales of assay kits and fee-for-service deals with collaborations like the announced Biodesix arrangement not "routine for us yet," van Sint Fiet said. "But we are continuously exploring this type of collaboration."
In addition to the Biodesix deal, the company has inked a similar collaboration with Swiss 3D cell culture firm Insphero, using the HRM technology to do mechanistic toxicology and efficacy studies.
"There again we collaborated combining our capabilities in a project where, basically, the application called for a bit of a deeper insight into the biology, and we were able to contribute with our proteomics technology," van Sint Fiet said.
In general, he said, Biognosys is seeing strong interest in its HRM method from pharma firms looking to use it for applications like target validation, mechanism of action studies, and mechanistic toxicology studies.
For Biodesix, the collaboration fits with its recent pattern of partnering to bring in outside technology as it seeks to expand the breadth of its offerings. For much of its existence, Biodesix has focused primarily on development of Veristrat and other MALDI-based tests for assessing likely responders to cancer therapy — mainly in lung cancer.
Over the last year, though, the company has broadened its portfolio to include genomic offerings. For instance, in March it announced that it had entered a partnership with UK-based genomics firm Inivata to develop and commercialize a next-generation sequencing-based blood test for clinical use in lung cancer.
In April, it launched its PCR-based GeneStrat test for measuring BRAF, KRAS, and EGFR mutations in first-line NSCLC patients.
The Biognosys deal, Beresford suggested, can be see as part of this larger shift.
"I think our overall strategy is to bring in platforms that we believe can help us address clinical questions," he said. "We're looking at all these questions that go from diagnosis, prognosis, therapeutic monitoring, all the way to triage, and we have added the tools to address these questions."