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Biodesix IDs Proteomic Signature for Predicting Response to GlobeImmune Pancreatic Cancer Therapy

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Biodesix this week presented data indicating that a proteomic signature identified using the company's ProTS mass spec-based system can identify pancreatic cancer patients likely to respond to treatment with GlobeImmune's GI-4000 therapy.

Presented at the European Society of Medical Oncology's 14th World Congress on Gastrointestinal Cancer, the findings emerged from a collaboration between the two companies focused on developing a companion diagnostic to support GI-4000's clinical development and, ultimately, its clinical implementation.

This marks the first time Biodesix has reported results from a pharma partnership using its technology to develop a proteomic signature linked to patient response to a particular agent.

The company has evaluated its Veristrat serum proteomic test as a potential companion diagnostic for a number of drugs – particularly in non-small-cell lung cancer patients – but it has not to date released findings on any tests developed in collaboration with a specific pharma partner.

The GlobeImmune partnership "is different from what we have done with Veristrat," David Brunel, Biodesix CEO told ProteoMonitor. "With Veristrat we are identifying the state of a particular solid tumor, and it just so happens that we find different responses to drugs in the groups that we identify."

The GI-4000 work, on the other hand, focused specifically on that agent and its performance in pancreatic cancer patients. Biodesix identified the signature through an analysis of GlobeImmune's Phase II clinical trial for the agent.

The Biodesix researchers identified the signature via mass spec analysis of baseline plasma samples from 90 trial subjects. Using it they were able to predict late- versus early-recurrence in patients treated with GI-4000 as well as better and worse overall survival. Notably, the signature did not predict recurrence or survival in patients treated with a placebo.

GI-4000 is an immunotherapy that uses heat-inactivated S. cerevisiae expressing seven common Ras mutations in human cancers. The treatment is aimed at the roughly 90 percent of pancreatic cancers positive for Ras mutations.

GlobeImmune is also investigating GI-4000 as a treatment for non-small cell lung cancer and colorectal cancer. Brunel said Biodesix has "had preliminary discussions" about working on proteomic signatures to measure the therapy's effectiveness in those cancers as well but hasn't "yet launched that process."

The companies are currently involved in discussions about moving the identified signature "to the next stage of doing a validation study," Brunel added, with the ultimate goal of using the signature to help select patients for future GI-4000 clinical trials and, "if the drug is approved [by the US Food and Drug Administration], to potentially use it to identify patients who would receive the greatest benefit" from the therapy.

While Biodesix offers Veristrat, which it launched in 2009, as a laboratory-developed test out of its CLIA lab, the different nature of the GI-4000 signature's development will likely lead the company to pursue a different regulatory path, Brunel said, noting that if a companion diagnostic does emerge from the collaboration, Biodesix would probably take it through the FDA approval process.

"Certainly the FDA would prefer that if there were a diagnostic used to guide patients to a particular therapy that that classifier or diagnostic went through [premarket approval] and did that at the same time the drug was going through [FDA]," he said. "Likely we would endorse that approach in this context. Because it's early days with what we're identifying, and because we've identified it with a partner, I think it would make sense for us to advance this project [through FDA] together, and that is different from what we've done with Veristrat."

The partnership doesn't necessarily signal any larger shift in the sort of collaborations Biodesix aims to pursue with its technology, though, Brunel said.

"We have what we think of as a very differentiated discovery platform, and we're willing to collaborate on a number of different models in order for us to discover clinically useful classifiers," he said. "So where we've done that with a particular partner as with GlobeImmune, it looks different from Veristrat, but [both are] consistent with our business model."

Aside from the GlobeImmune partnership, Biodesix has a number of ongoing collaborations including 14 deals with pharma and biotech firms investigating the usefulness of Veristrat as part of various therapeutic programs. All told, it has collected data on Veristrat from more than 2,500 patients across 25 clinical trials.

Most recently, the company announced it was collaborating with pharma firm Kadmon on a 620-patient Phase III clinical trial of that firm's reversible tyrosine kinase inhibitor KD019 (PM 3/2/2012). It also recently completed enrollment for its PROSE prospective trial, which will evaluate Veristrat in investigations of 275 NSCLC patients, comparing treatment with the Genentech EGFR inhibitor Tarceva versus standard of care. It aims to present the results of the study at a meeting in either the latter half of this year or early 2013.

Biodesix's ProTS discovery system is based on MALDI mass spec, specifically Bruker's autoflex instruments. It identifies general proteomic signatures in serum, rather than specific proteins or peptides.

The company, Brunel said, is interested in identifying the specific analytes underlying its predictive signatures "as time and resources and collaborations with other scientists allow." However, he noted, "our primary objective is to first and foremost discover these signatures and validate them and try to get them into the clinic as quickly as we can."

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