Caris Life Sciences and Threshold Pharmaceuticals said today they will use Caris’ liquid biopsy platform for identifying novel diagnostic and therapeutic targets to develop a tissue-based clinical diagnostic assay designed to predict the likelihood of response to Threshold’s lead cancer drug candidate in pancreatic cancer patients.

The collaboration—which the companies said was valued at up to “several million dollars”—will combine Caris’ proprietary ADAPT Biotargeting System with Threshold’s lead cancer drug candidate evofosfamide (TH-302). The companies said they will study tumor samples and outcomes data from the previously completed Phase III MAESTRO study in patients with advanced pancreatic cancer, and develop a novel, multiplexed diagnostic assay designed to classify a patient's likely clinical outcome from the use of evofosfamide.

Evofosfamide is an investigational, Threshold-discovered, hypoxia-activated prodrug of a DNA cross-linking agent that is preferentially activated under hypoxic tumor conditions, a feature of many solid tumors. Evofosfamide is in Phase II development for both non-small-cell lung cancer and head and neck squamous cell carcinoma.

Threshold regained rights to evofosfamide from Merck KGaA in January, a month after acknowledging that the candidate failed two Phase III trials by not showing statistically significant improvement in overall survival in advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma.

Threshold saw its stock value crater 82% on December 7, placing the company on GEN’s list of Top 10 Wall Street Losers of 2015. The company slashed its workforce by two-thirds in December 2015, leaving it with 20 to 25 employees, following the Phase III disappointments.

However in one of those trials, the pancreatic cancer-focused MAESTRO study, Threshold said data also showed meaningful improvement in overall survival in a subgroup of 116 patients from Japan, in which the risk of death was reduced by 48% for patients receiving evofosfamide compared to patients in the control arm.

“We remain optimistic about the potential role of evofosfamide for the treatment of cancer, and we continue to pursue discussions with Japanese regulatory authorities regarding potential registration pathways for evofosfamide and other development opportunities with evofosfamide,” Threshold CEO Barry Selick, Ph.D., said in a statement.

Threshold said September 29 it would refocus on development of evofosfamide as well as an earlier-stage anticancer candidate, TH-3424, while halting development of another candidate, tarloxotinib, following results in a pair of Phase II trials that failed to meet expectations.

ADAPT is designed to characterize complex biological systems by using libraries of synthetically manufactured molecules trained to bind to biological targets of interest. The platform is now being applied in discovery research, advanced diagnostics, and drug development programs across multiple diseases—but according to Caris, also has potential uses in drug delivery, disease monitoring, and direct therapeutic applications.

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