NEW YORK (GenomeWeb) – Diagnostics firm Biodesix is moving beyond proteomics testing and into the genomics space, Paul Beresford, the company's vice president of business development and strategic marketing told GenomeWeb this week.
The company, which said this week that it added $12 million in follow-on financing to a series E round that raised $15 million in 2013 and 2014, plans early this year to launch a droplet-based digital PCR-based test for measuring three genes – BRAF, KRAS, and EGFR – in the plasma of lung cancer patients. The firm is also at work on a next-generation sequencing panel that could be used for guiding therapy in late-stage lung cancer patients and longitudinal tracking of mutations in patients over the course of treatment, Beresford said.
He added that Biodesix is continuing its proteomic product development and is in the process of taking a new version of its Veristrat lung cancer test through US Food and Drug Administration premarket approval as part of its ongoing partnership with drugmaker Aveo Oncology.
Veristrat, Biodesix's sole product, was launched in 2009 and uses MALDI-TOF mass spec and a set of proprietary algorithms to predict response to therapy in lung cancer patients based on their proteomic profiles.
The bulk of the company's work with Veristrat has focused on predicting response to EGFR tyrosine kinase inhibitors, and last year the National Comprehensive Cancer Network approved inclusion of the test in its guidelines for non-small cell lung cancer, recommending that it be used to determine whether NSCLC patients with wild-type or unknown EGFR status should receive Genentech's Tarceva (erlotinib) as a second-line treatment.
Biodesix has also used its MALDI-TOF-based ProTS discovery platform to identify proteomic signatures indicating likely response to other types of therapies, and, in fact, Beresford said that a primary focus in 2015 would be partnering with developers of immunotherapies to determine whether the company's technology could be useful in guiding such treatment. In 2012, the company presented data on a proteomic signature that helped identify pancreatic cancer patients likely to respond to GlobeImmune's GI-4000 immunotherapy.
The Aveo deal stemmed from a study in which the drugmaker used Veristrat as part of a Phase II study Aveo conducted several years ago in NSCLC patients evaluating the effectiveness of the combination of ficlatuzumab — a hepatocyte growth factor inhibitor — and the EGFR inhibitor gefitinib (AstraZeneca's Iressa) compared to gefitinib alone.
The ficlatuzumab-gefitinib treatment failed to reach its primary endpoint, but, using Veristrat, the researchers identified a subset of patients who appeared to benefit from the combined therapy.
Last year, the two parties entered an agreement to co-develop and commercialize ficlatuzumab with a version of Veristrat as a companion test to predict best responders.
Under the terms of the agreement, Biodesix will fund the first $15 million of the drug development effort with the expenses thereafter split evenly between the two firms. The two will split any profits from commercialization of the drug. Additionally, Biodesix is solely responsible for all development of Veristrat, including taking the test through US Food and Drug Administration clearance or approval, and the company will retain all revenues from sales of the test.
Beresford said this week that the companies have begun enrolling patients for a Phase II clinical trial testing the effectiveness of ficlatuzumab plus erlotinib versus erlotinib alone on NSCLC patients selected using a version of Veristat. Ultimately they plan to enroll around 150 patients across sites in the US, Europe, and Asia over the next 18 months.
Biodesix has also begun the process of taking the version of Veristrat used in the trial through FDA PMA. Beresford said the company will most likely submit the test on Bruker's Microflex LT MALDI instrument, which has received FDA 510(k) clearance as part of Bruker's MALDI Biotyper platform.
Assuming Biodesix does move the test through FDA PMA on the Microflex, it would be another significant milestone for MALDI as a technology for clinical proteomics. Traditionally, the field has viewed multiple-reaction monitoring mass spec on triple quadrupole instruments as the likeliest route for mass spec-based proteomics to move into clinical applications, with MALDI traditionally being dismissed due to concerns about its sensitivity and reproducibility.
However, while MRM-based proteomic assays are slowly making their way into the clinic, MALDI-based proteomic platforms – primarily Bruker's Biotyper and BioMérieux's Vitek MS have had even more clinical impact to date.
"MALDI-TOF has kind of been ignored, but based now on the success Bruker has had, I think it is perceived now as a real viable commercial play for these types of tests," Beresford said.
Also in preparation for the PMA submission, Biodesix has worked to nail down the specific peptides underlying the Veristrat signatures, he noted. The test has traditionally relied on differentiating between the mass spectra of different clinical samples as opposed to identifying and quantifying specific, known protein analytes, and, in the past, Biodesix has acknowledged that it has not identified all the analytes underlying the spectra generated by the test.
"We are in active discussions with FDA about how we are going to go forward with that sort of analytical validation," he said.
Beresford declined to give figures regarding Biodesix's revenues from Veristrat but said that the company has performed more than 12,000 tests since launching in 2009 and that in 2014 it roughly doubled the total number of tests performed.
Biodesix has decided to expand into the genomics space in part due to feedback from Veristrat customers, Beresford said. In particular, he noted, the company believes there is a need in the community practice setting for blood-based tests to assess mutation status in the three genes – BRAF, KRAS, EGFR – that will comprise the PCR-based panel it plans to launch later this year. The company plans to use Bio-Rad Droplet Digital PCR instruments for this work, Beresford noted.
"With about a third of patients, [clinicians] aren't able to obtain tissue biopsies or they have insufficient material to do molecular tests, so a blood-based version of those tests really meets an unmet need for those patients," he said. "It's an additional test in that first-line setting before they go into therapy."
"Then as they progress off first-line and go into second-line, that is where we position Veristrat as a tool to help them make better decisions in that second line," he added.
"We have a fully integrated molecular diagnostics play that includes a commercial sales force that is calling on oncologists," Beresford said. "And because we have that continuous integrated play and a commercial organization [in place], we believe we have a window of opportunity to drive forward blood-based versions of these molecular tests."
Biodesix's NGS work is more exploratory, he said, noting that the company plans to look at around 30 to 40 genes in plasma and hopes to engage academic and biopharma partners to determine the clinical utility of such a panel in determining treatment for late-stage patients and monitoring genetic changes and the development of resistance in response to treatment.
Beresford added that Biodesix will undertake this NGS effort in collaboration with a partner "that is very well known in the NGS space and has been actively researching these types of questions in plasma." He said the company will likely identify the partner in the first quarter of the year.
Ultimately, Beresford said, the company aims to combine these multiple levels of information.
"One can imagine down the road as we develop tests that we will pull in not just proteomic features but genomic features to create a master classifier, if you will, for drugs or a prognosis or diagnosis," he said.