AUSTIN, Texas (GenomeWeb) – At the annual meeting of the Association for Molecular Pathology this week, HTG Molecular Diagnostics provided updates on its pipeline of NGS cancer assays, including plans to launch a lung cancer fusion panel by the end of this year.
During its corporate workshop at the meeting, HTG also featured a presentation by University of Southern California professor Pamela Ward, who discussed a pilot project using HTG's EdgeSeq microRNA whole transcriptome assay — covering 2,275 microRNAs — in an attempt to develop a classifier to more accurately subtype patients with ovarian cancer.
HTG’s technology is essentially a library preparation method that allows for much smaller sample inputs than other platforms, mainly by eliminating steps like DNA extraction from the sample preparation process.
The company launched the EdgeSeq miRNA Whole Transcriptome Asssay, its first NGS-based assay, earlier this year. And last year HTG also announced an agreement with Illumina to develop in vitro diagnostic kits for clinical sequencing assays.
At AMP this week, Patrick Roche, HTG’s head of development, updated attendees on how the company's pipeline has expanded in recent months.
In addition to the miRNA assay, HTG also currently offers a test for FGFR expression and a large, RNA-based oncology panel that includes more than 2,500 genes.
The company also sells a panel measuring expression of 93 genes frequently assessed with lymphomas, a more specific assay to subtype patients with diffuse large B-cell lymphoma into one of two "cell of origin" subtypes, and finally, an immune-oncology panel comprised of probes targeting 549 genes implicated in the host immune response to various tumors.
All of these offerings are currently research-use-only assays, adaptable for both Illumina and Ion Torrent sequencers, Roche said at the meeting.
Particularly with regard to the immuno-oncology panel, Roche said that HTG is seeking pharmaceutical and academic partners. Meanwhile, the company said that it is already engaged in several collaborations using its DLBCL cell of origin test.
With the advent of drugs targeting one or the other DLBCL COO subtype — either ABC or GCB — many academic groups and companies have been advancing technologies for patient subtyping. For example, researchers are using Illumina's DASL platform to assay 20 genes in a trial called REMoDL-B to provide equal proportions of ABC and GCB patients for randomization with either R-CHOP chemotherapy alone or R-CHOP plus the drug bortezomib (Takeda's Velcade).
A separate Phase III trial, ROBUST, is evaluating the efficacy of adding the Celgene drug lenalidomide (Revlimid) to R-CHOP in patients with ABC DLBCL as determined by NanoString's assay Lymph2Cx.
NanoString announced last year an agreement with Celgene to develop the test as a companion diagnostic test for Revlimid and said it intends to seek regulatory approval of the test following completion of the Revlimid DLBCL trial.
A number of other technologies have also been adopted for DLBCL subtyping, for example, Cleveland Clinic researchers have developed an RT-PCR method using Primera Dx's ICEPlex system, now Qiagens' Modaplex, which is currently available for patients through the clinic's reference lab. Some of the Cleveland Clinic's experience adapting and adopting Modaplex for DLBCL subtyping was also shared at the AMP meeting this week.
Roche did not detail any of HTG's current collaborations or highlight research using its own new DLBCL test during the workshop, but when asked by an audience member, Robert Boorstein of the ClasGroup Company, about how the assay compares to NanoString's Lymph2Cx, he claimed that HTG's test "requires less input, and has a faster turnaround time."
In addition to its currently available assays, Roche also said at the meeting that HTG plans to launch before the end of the year a panel for detecting gene fusions with relevance to lung cancer treatment, including ALK, ROS, and RET, as well as HER2 insertions that occur in a small percentage of lung cancers.
According to Roche, fusion detection using HTG's platform involves the use of probes that target the 5' and 3' ends of the fusion product. If no rearrangement is present, expression of the two ends will be equal, whereas if there is overexpression of the 3' end relative to the 5', this indicates the presence of a gene fusion.
In addition to this strategy, the assay also included specific probes for all the published fusion junctions themselves, a secondary, complementary detection method.
During the presentation, Roche said that HTG expects to launch the lung fusion panel by the end of this year. The company is also working on a fusion panel for hematologic cancers, a more general solid tumor fusion test, and on adapting its technology to allow not just fusion detection but also targeted sequencing of somatic DNA mutations.
Asked about HTG's plans for developing clinical-use kits for approval by the US Food and Drug Administration or other regulatory bodies, Roche said that the agreement with Illumina includes a plan for developing a PMA version of the HTG lung fusion panel. He added that the company expects to move through the process for a launch of this test in late 2017 or 2018.
HTG also intends to seek CE-IVD marking of its DLBCL test, but doesn't have any other regulatory plans at this time, Roche said.
Ovarian cancer pilot
Following Roche's update on HTG's pipeline, USC professor Pamela Ward also shared data from a pilot project investigating whether HTG's EdgeSeq microRNA whole transcriptome assay could be used to develop a classifier to more accurately subtype patients with ovarian cancer into clear-cell, serous, and endometrioid types.
Ward and her colleagues, as part of a study in collaboration with Response Genetics, hypothesized that a miRNA expression signature could improve the diagnostic accuracy of current histopathological methods.
Though specific molecularly targeted treatments are not yet available for different ovarian cancer subtypes, knowing the correct type of cancer can be crucial in getting patients on the appropriate clinical trial, Ward explained. However, histopathology isn't all that good at distinguishing one type of ovarian cancer from another.
"Given this diagnostic dilemma, we thought that expression profiling of 22,000 microRNAs could help," she said in her presentation. To that end, she and colleagues collected non-contentious samples of endometrioid, clear-cell, and serous ovarian cancers — 50 cases in all — and tested them using HTG's assay.
Statistical analysis by the company identified 40 miRNAs that were differentially expressed between the three tumor types the group studied. Plotting data from a principle component analysis, the researchers were then able to show a segregation of clear-cell cancers, as well as a segregation of serous and endometrioid cancer albeit with significant admixture between the two.
The small study was not able to generate a clinically useful classifier, Ward said, but she and her colleagues hope to be able to do so with a larger sample set.
"We had hoped to generate a classifier but only had 50 cases," she said. "We really need more like 200, so this was just a pilot experiment."