NEW YORK – ChromaCode has begun to apply its qPCR multiplexing technology to digital PCR (dPCR) and cancer diagnostics, recently launching a highly multiplexed tissue-based test for genetic mutations in non-small cell lung cancer. The launch is part of an overall strategic pivot to focus on multiplexed dPCR-based oncology and transplant testing, according to the firm.
As part of its new focus, ChromaCode's board of directors in January brought on Mark McDonough as CEO. His genomics and oncology experience comes from leading CombiMatrix until it was acquired by Invitae, as well as serving as chief business officer at Phosphorus and CEO of Immunis.AI. He was most recently CEO of PierianDx until that firm was acquired by private equity firm Summa Equity.
ChromaCode also brought in Padma Sundar to be its chief business officer. Sundar has held oncology product marketing positions at Affymetrix, Roche, Guardant Health, CellMax Life, and Oncocyte.
With this team in place, earlier this month ChromaCode launched its first oncology test kit — a non-small-cell lung cancer assay that uses dPCR to detect actionable NSCLC variants in nine genes. The test has a simplified workflow, uses cloud-based analysis, and can generate results in less than four hours. The firm also posted a study to the preprint server BioRxiv in May describing the test's analytical performance and showing a 97 percent accuracy compared to next-generation sequencing.
In an interview, McDonough also said that the new test is advantageous for patients and clinicians compared to sequencing because it only needs 20 ng of biopsy tissue rather than the 40 to 100 ng needed for sequencing.
The Carlsbad, California-based company now plans to focus on oncology, McDonough said, but will also develop assays in the transplant diagnostics space.
ChromaCode's core technology, called high-definition PCR (HDPCR), uses machine learning algorithms and novel chemistries and methods to increase multiplexing capabilities of standard lab instruments. Where most systems can detect one or two analytes in a single color channel, ChromaCode uses limiting concentrations of probes so that multiple targets can be detected per channel based on their different fluorescence intensities. In 2021, a study in Analytical Chemistry showed that the approach could be used to expand standard qPCR instruments so that they could detect up to 20 targets per well.
Although ChromaCode has described its oncology intentions from the outset, it initially entered the in vitro diagnostics market with qPCR test kits for multidrug resistant infections and tick-borne diseases.
ChromaCode then developed a SARS-CoV-2 assay that was granted Emergency Use Authorization by the US Food and Drug Administration in June 2020. The test cost $25 per sample, with up to 380 tests run simultaneously in under two hours, enabling labs to process approximately 10,000 samples per day.
The firm also won a $1 million XPrize in 2021 for this approach, further enabling it to accelerate the adoption of its testing.
Between 2020 and early 2022, "we ran 7 million tests through the ChromaCode cloud," said McDonough.
In 2021, ChromaCode executives said the future menu would include other infectious diseases, noninvasive prenatal testing, and oncology. But, as the pandemic has waned, the firm began sunsetting the COVID testing, and from there, "we saw a tremendous opportunity to leverage the value of the IP in genomics," McDonough said.
In April, ChromaCode forged a partnership with MedGenome to distribute the NSCLC assay in India and the Middle East. Vedam Ramprasad, CEO of MedGenome India, said in an email that the partnership reinforces his firm's commitment to advancing precision diagnostics in emerging markets.
"Leveraging ChromaCode's cloud-based workflow, we can now present a distinct and competitive product with swift turnaround times," Ramprasad said, adding that a key highlight of the NSCLC test is that it effectively detects variants in all National Comprehensive Cancer Network-recommended genes for NSCLC profiling with minimal sample input.
Pivoting
The pivot to oncology and genomics also includes a shift toward dPCR multiplexing, as opposed to qPCR.
ChromaCode has so far validated and optimized its NSCLC kit on the Qiagen QiAcuity system, McDonough said.
The firm intends to expand this validation to include other digital PCR systems, for example those from Bio-Rad, Roche, and Stilla Technologies. "We're platform agnostic with our solutions," McDonough noted.
ChromaCode also presented data at the American Association for Cancer Research meeting last year on the use of the HDPCR technology with the Thermo Fisher Scientific Absolute Q digital PCR system. In a poster, it showed its NSCLC assay on the Absolute Q had a limit of detection as low as 10 variant copies in a background of 10,000 haploid human genome DNA copies.
The firm is positioning its dPCR solutions as alternatives to single-gene qPCR tests and sequencing, with higher sensitivity and more comprehensive results than the former, and lower cost and faster throughput than the latter, particularly when considering the capital expenditure required for in-house sequencing.
That said, ChromaCode also recommends sequencing in cases for which the dPCR panel does not detect a mutation. The company is currently working on a health economics study to demonstrate that using its NSCLC test upfront of sequencing is overall less costly to healthcare systems than performing sequencing alone, even when the combination of dPCR panel and sequencing is required for as many as half of all cases.
For lung cancer specifically, McDonough said that patients with positive imaging results could potentially have an actionable dPCR panel test result in two hours that can help clinicians make more tailored treatment decisions. The fast turnaround time also potentially spares patients and families a lot of angst waiting on results, he said, and allows them to possibly access therapies with fewer side effects.
Similarly, an in-house dPCR transplant test saves time compared to standard send-out sequencing-based testing, McDonough said.
ChromaCode is currently building up its commercial team and increasing its sales and marketing efforts in oncology and transplant diagnostics. This includes an increased presence at conferences such as the American Society of Clinical Oncology, the Association for Molecular Pathology, and the American Transplant Congress, as well as dedicated lung cancer meetings, McDonough said.
The next steps in oncology will likely be assays for therapy selection as well as solid tumor and minimal residual disease tests that are being developed with partners in the clinical research space, McDonough said. The firm is also in the proof-of-concept stage for its transplant testing.
And, in addition to oncology and transplant, ChromaCode is growing its custom-tailored assay business through collaboration with providers and academic medical centers.
ChromaCode recently added to its $38 million Series D funding with strategic investment of undisclosed amounts from Japanese funders Shimadzu and Meiji Yasuda Future Innovation Fund.
The firm also remains open to partnering for further commercialization of assays in the infectious disease and NIPT spaces, McDonough said.
But "we've really pivoted to where we think we're the strongest," he said. "For our own efforts, we see the best value is oncology and transplant."