In this interview, Chris Roberts of Aventa Genomics highlights the groundbreaking Aventa FusionPlus test, detailing its superior ability to detect gene fusions in cancer diagnostics and its pivotal role in advancing personalized oncology treatments.

Could you give us a brief overview of Aventa Genomics, including its founding vision and primary mission in the field of genomics?

Many patients with cancer undergo testing to identify genomic variants that can be targeted by personalized cancer drugs. Unfortunately, traditional next-generation sequencing-based and FISH tests often miss gene fusions and rearrangements present in cancer that can a) resolve diagnostic dilemmas or b) be targeted with therapies on the market or in clinical trials. Aventa Genomics was founded to develop and commercialize 3D genomics-based tests to improve upon conventional methods.

Aventa Genomics is a joint venture between Arima Genomics and Protean BioDiagnostics. What synergies between these two companies led to the formation of Aventa Genomics, and how do these synergies drive the company’s innovation and research?

The two companies have complementary competencies. Arima Genomics is fundamentally a technology company, and Protean BioDiagnostics is a clinical laboratory testing company.

How does Aventa Genomics aim to transform patient care in oncology? What specific gaps in the current healthcare system is Aventa addressing with its technologies?

Aventa Genomics has commercialized the Aventa FusionPlus test, which enables any oncologist or pathologist, whether in a highly specialized comprehensive cancer center or a community hospital, to offer patients access to a genomic test able to identify gene fusions and other rearrangements that may be missed by conventional NGS and FISH tests.

Aventa FusionPlus is a genome-wide test and bioinformatically filters to report variants in 361 genes that are potentially actionable in solid tumors.

Can you describe how the Aventa FusionPlus test differs from traditional gene sequencing methods like FISH and RNA sequencing, particularly in its approach to detecting gene fusions, translocations, and rearrangements?

Both RNA sequencing and FISH methods can be utilized for the detection of gene fusions and rearrangements, but each method has limitations. RNA sequencing is limited to identifying gene fusions and rearrangements that produce a fusion transcript. However, in many cases, the breakpoint for a potentially actionable variant is in a non-coding region, and therefore no fusion transcript is produced. Another limitation of RNA, as a molecule, is that it is labile and often degraded in clinical specimens and can result in an insufficient quantity for sequencing.

FISH tests typically identify only one gene rearrangement at a time, and it is not practical, from a tissue availability perspective, or economical, to perform more than three or four FISH tests on a single specimen.

In our experience, when RNA sequencing or FISH finds a gene fusion or rearrangement, we find it as well. The power of the Aventa test is that it also identifies the gene fusions and rearrangements that RNA sequencing or FISH either did not or cannot detect.

The Aventa FusionPlus test utilizes 3D genomics technology. Could you explain the significance of preserving the spatial proximity of fused and rearranged genes and how this contributes to the 100 to 1000-fold signal amplification in detecting gene variants?

The Aventa FusionPlus test works by first crosslinking DNA in intact nuclei and then wherever two strands of DNA are in close proximity to each other, ligating them together, creating a molecule that has DNA from each of the two strands. When two genes are rearranged, we see hundreds or even thousands of contact points where the genes are in close spatial proximity. In contrast to conventional sequencing methods, which only see the breakpoint, we see the breakpoint plus these additional, informative signals that enable the identification of a fusion.

In previously characterized tumor specimens with no known actionable driver, the Aventa FusionPlus test detected potentially actionable variants in half of the cases. How does this increase in diagnostic yield translate into clinical benefits for patients?

The patients whose test results indicate potentially actionable variants can access targeted therapies or be enrolled in clinical trials that their oncologists might not have been able to identify without this testing.

How does the Aventa FusionPlus test improve upon the limitations of existing genomic testing methods? Are there specific types of cancers or stages where this test is particularly beneficial?

Physicians are using the Aventa FusionPlus test to a) resolve diagnostic dilemmas in translocation-driven cancers like sarcoma and b) identify targetable fusions in genes like NTRK and ALK. The majority of the cases we see are advanced cancers.

What do you foresee as the future role of 3D genomics in patient diagnosis and therapy selection?

We expect 3D genomics-based tests to become an integral part of the standard workup for patients with advanced cancers.

How accessible is the Aventa FusionPlus test for physicians and patients? Are there any geographical or logistical limitations in its availability?

Oncologists and pathologists can order the Aventa FusionPlus test. We are pursuing reimbursement in the U.S. via Medicare and commercial insurance payers, akin to other genomic-based cancer tests. Test requisition forms are available at www.aventagenomics.com.  

How do you see the Aventa FusionPlus test contributing to the field of personalized medicine and improving patient outcomes?

We believe the test will be able to identify new biomarkers of response, as well as resistance, to on-market therapeutics. We also see this test as a mechanism to accelerate clinical trial enrollment due to the additional diagnostic yield of gene fusions and rearrangements.

What are the future goals for Aventa Genomics, and can we expect any new tests or technologies in the near future?

The Aventa FusionPlus test is indicated for solid tumors. We are in the process of developing a test for hematological malignancies.

Where can readers find more information?

About Chris Roberts

Chris Roberts is the Executive Director of Aventa Genomics, where he is responsible for the management of the organization. He is also the SVP of Corporate Strategy for Arima Genomics, which is one of the parent companies of Aventa Genomics (along with Protean BioDiagnostics).

Prior to this role, Chris held leadership positions at Decipher Biosciences (acquired by Veracyte), HTG Molecular, Caris Life Sciences, and Ventana Medical Systems (acquired by Roche).