NEW YORK – Molecular diagnostic startup GeneCentric Therapeutics is about to launch a phase II validation study with Washington University in St. Louis as part of its efforts to commercialize a companion diagnostic for HPV-negative head and neck squamous cancer (HNSCC) for both prognostic and predictive applications.
The Research Triangle Park, North Carolina-based firm is developing a targeted biomarker panel that detects genetic mutations in mesenchymal cells, with the goal of guiding drug treatment for patients who would benefit from earlier intervention.
Cofounded in 2012 by David Hayes, a University of Tennessee pathology professor, and Charles Perou, a cancer researcher at the University of North Carolina, Chapel Hill, GeneCentric has expanded the researchers' original discovery of molecular signatures associated with lung cancer subtypes to other cancer types.
According to GeneCentric President and CEO Mike Milburn, the HPV-negative subtyping test the researchers are developing is a modified version of the firm's Head and Neck Cancer Subtype Profiler, which examined around 1,000 genes. The firm's original Cancer Subtyping Platform (CSP), based on intellectual property licensed from Hayes' lab at UNC, examined publicly available gene expression datasets to create narrow sets of genes that define cancer subtypes. By testing and validating genes linked to each cancer, GeneCentric develops tumor-specific clinical assays.
After discovering the gene set for a specific assay, GeneCentric's team then sees how the set performs on patient FFPE tumors, potentially leading to drug development informed by the genomic-defined cancer subtypes. Milburn argued that FFPE acts as the most "readily available sample type that provides the most accurate information for our subtype tests."
After collecting FFPE samples from patients, GeneCentric's team extracts RNA using a number of commercial RNA isolation methods and kits. The researchers then use whole-transcriptome sequencing or RNA-seq to discover specific gene signature or gene sets. However, Milburn noted that researchers can also apply a variety of technology platforms such as quantitative PCR to measure the presence of genetic biomarkers linked to the specific cancer.
In 2017, GeneCentric partnered with Hayes and Jose Zevallos, an associate professor at WUSTL, on a five-year, multi-phase $390,000 National Cancer Institute-funded project to develop, validate, and commercialize a four-class molecular subtyping diagnostic for HPV-negative HNSCC. The team is trying to link molecular markers and clinical feature data of specific HNSCC subtypes to produce a clinically relevant assay, which the firm believes will provide improved prognostic and predictive results for guiding cancer patient care.
In Phase I of the study, the group defined a 144-gene signature that they associated with the four HPV-negative HNSCC subtypes: basal, classical (CL), mesenchymal (MS), and atypical. According to Milburn, the researchers wanted to find the reproducibility and accuracy of the smaller gene set. Each subtype exhibits distinct differences in cell origin, tumor drivers, proliferation, prognosis, and host immune response.
"Now we want to take that information and see how well it performs and identify certain subtypes that could be more medically relevant, in terms of being commercialized," Milburn said.
After completing the Phase I study in the first quarter of this year, Zevallos' team began collecting patient samples for the Phase II study. The researchers will examine the potential of using MS cells to monitor HNSCC progression, as they believe that the subtype is more aggressive and linked to a higher likelihood of metastasis.
"[By] identifying that cancer subtype and working with a pharma partner to develop [a biomarker signature] with better clinical utility and later commercialize it, we can guide better drug treatment to patients who would benefit" from earlier intervention, Milburn explained.
After extracting RNA from about 400 FFPE samples from HNSCC patients, the team will use whole-transcriptome sequencing to discover and develop targeted gene signatures for the HNSCC subtype.
The researchers' major goal of the Phase II study will be to identify patients with occult lymph node metastasis in the MS subtype, as well as to see if cases of HNSCC CL subtype are linked to radiation therapy resistance. Milburn anticipates that the team will finishing sequencing samples by early 2020.
After completing Phase II, the researchers will start the Phase III study by implementing the targeted assay in clinical cancer patient cohorts. Milburn said that the team will first develop the assays on an unspecified platform that it has selected for the study, followed by analyzing the Phase II samples and newly collected ones using the targeted diagnostic platform, comparing performance to the discovery datasets. The team will then independently validate the HPV-negative HNSCC assay on new test samples and establish its test performance characteristics.
GeneCentric plans to partner with a biotech or pharmaceutical firm to further develop and commercialize a panel for guiding patient-specific treatment in cases of the MS subtype of HNSCC. GeneCentric previously partnered with LabCorp and Bristol-Myers Squibb to develop targeted cancer companion diagnostic assays, and both firms have subsequently made equity investments in the firm. Milburn believes that both firms would be potential candidates for the HNSCC subtype assay in the future.
"We believe that pharmaceutical or biotech groups could use these subtype assays as a biomarker tool for their drug development program, and this will be a big focus as we continue to develop the profilers," Milburn said. "We see an opportunity for late-stage compounds for both the drug [development] and companion diagnostic [sectors]."
GeneCentric also announced today that it has acquired Chapel Hill, North Carolina-based Select ImmunoGenomics as part of its goal to expand its genomic solutions business. The acquisition will provide the combined firm with integrated RNA-based tools to enhance drug development by identifying the right patients for oncology drugs, improving response rates and durability as well as eventually patient outcomes.
Financial details of the agreement were not disclosed. Milburn added that the acquisition will have "tremendous" synergy with the firm's ongoing HNSCC study.