NEW YORK – Startup Savran Technologies aims to detect disease recurrence in triple negative breast cancer (TNBC) patients with its microfluidic platform, which isolates and quantifies circulating tumor cells (CTCs). The company believes the method could complement circulating tumor DNA (ctDNA)-based approaches to monitor for minimal residual disease (MRD). Â
Savran Technologies expects to integrate the microfluidic chip with a ctDNA assay offered by a liquid biopsy partner, with a goal to launch the combined platform in the US by 2022.
Spun out of Purdue University in 2018 by CEO Cagri Savran, the firm currently has a lab in Boston. Savran explained that his team's microfluidic platform stemmed from his thesis work on micro- and nano-sensor interfaces and their biological and medical applications at Massachusetts Institute of Technology.
As a professor of mechanical and bioengineering at Purdue, Savran began developing the microfluidic chip to capture and analyze rare cells. His team at Purdue is now collaborating with Indiana University researchers to further develop the technology.Â
Previously detailed in a JAMA Oncology study in July, Savran's method involves a custom antibody-based, positive-selection microfluidic device to enumerate CTCs.
After extracting 10 ml of a patient's blood sample, Savran's team uses magnetic beads conjugated with antibodies against a specific antigen to capture cells overexpressing the antigen. The target-bound beads then flow through a silicon microfluidic chamber and are drawn to a microchip by an external magnetic field. The rare cells and molecules captured on the surface are quantitatively analyzed using fluorescent microscopy.
In the study, the investigators used Foundation Medicine's FoundationOne Liquid and FoundationACT liquid biopsy assays on blood samples from TNBC patients following standard neoadjuvant treatment to profile ctDNA and enumerated CTCs using Savran's microfluidic device.
The researchers saw that the sensitivity to detect breast cancer recurrence across the cohort was highest when using both CTC and ctDNA-based markers: the integrated method's MRD sensitivity was 79 percent with ctDNA alone, 62 percent with CTCs alone, and 90 percent when combined.
"Our CTC assay was combined with the [ctDNA] assay to see if it [would] bolster the ctDNA-alone test," Savran said. "The combined ctDNA [and] CTC test showed it to be a superior predictor of recurrence to most[ly] anything else." Â
Patients who were both ctDNA-positive and CTC-positive had inferior distant disease-free survival, compared to patients who were double-negative. While the authors noted the results do not currently support using liquid biopsy to guide routine clinical practice, they believe that the data supports use of the MRD strategy in post-neoadjuvant clinical trials.
Savran and his colleagues now plan to launch validation trials, led primarily by his colleagues at Indiana University. However, he declined to discuss further details on the upcoming studies.
While Savran's team applied EpCAM as a biomarker in the study, he believes that the platform can use a cocktail of antibodies to identify potential biomarkers in breast and other cancer types.
"If you're going after different types of tumors that have antigens that are different from EpCAM, or if you suspect that the cells have less EpCAM and more of another antigen, you can add different antibodies," Savran said. "The technology is very adaptive from that perspective."
Savran said that his team has developed modules on the platform that allow for additional features, including single-cell extraction for DNA analysis. The group has also automized parts of the process, including reagent addition and control of different flow parameters.
"[Flow parameter control] is super important because it prevents 'babysitting' the workflow, helps improve training and reduces user-to-user variation, and allows running multiple assays in parallel," Savran explained.
Savran Technologies will initially develop the technology further to help predict cancer recurrence, especially in early-stage breast cancer. However, he anticipates that the platform will enable highly useful tests to monitor a patient's progress and response to therapy in several cancer types, including lung, prostate, and colorectal cancers.
In addition to cancer-based applications, Savran believes the platform could be applied in the prenatal field. He envisions potentially using the same fundamental technology, "albeit with a different assay," to capture rare fetal cells.
"Just like rare CTCs entering the bloodstream in a cancer patient, rare fetal cells enter in [the] blood circulation of a pregnant mother," Savran explained. "The advantage of capturing a whole fetal cell is that it would give you access to the entire intact genome of the fetus without a background, as opposed to the current non-invasive [cell-free] DNA-based tests that gives you fragments of DNA … in a huge background."
The US Patent and Trademark Office has issued Savran's team four patents related to the core technology that the company is exclusively licensing from Purdue University. The firm has also independently filed for patents related to the use of the technology, including almost a dozen in the US, Europe, China, Japan, and Canada.
Savran's team has not yet decided the path that it will follow to commercialize an assay in the US. While declining to comment as to whether the firm will offer a laboratory-developed test or apply for a 510(k) clearance with the US Food and Drug Administration, Savran believes that one viable option is to seek a breakthrough device designation from the FDA. Â
At the same time, Savran expects to partner with an existing company in the liquid biopsy space to integrate his team's microfluidic chip with a ctDNA-based test, such as Foundation's FoundationOne Liquid assay. The startup is also speaking with undisclosed parties to distribute and market its technology, with an envisioned goal of launching the test in the US in one to two years.
To support these efforts, the company has completed three private financing rounds for undisclosed amounts and expects to close an additional round "very soon." Savran declined to disclose the total amount of funding raised so far.
Several firms and research groups are developing their own CTC-capture technologies for applications such as cancer recurrence monitoring and MRD detection. Angle's Parsortix cell-sorting microfluidic platform captures CTCs based on their physical properties, including size and deformability. The firm is now working with BioView to detect CTCs in breast and lung cancers.
Menarini-Silicon Biosystems published research on Monday that it believes demonstrates the clinical utility of its CellSearch CTC platform to guide frontline therapy choice for patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. The firm believes that the study's results provide evidence that CTC count can support physicians when making effective treatment decisions.
Canadian startup Cellular Analytics' CytoFind assay uses single-cell mRNA cytometry and immunomagnetic separation to identify and sensitively capture CTCs. While initially focusing on lung cancer and mesothelioma, the firm has also performed exploratory work in breast and renal cancer.
While Savran declined to compare his team's technology to assays from competitors in the liquid biopsy space, he believes that the company's platform stands out because of its unique streamlined design and workflow.
"The [workflow] enables scalability in production and in handling a high demand [of samples], all without compromising … purity and sensitivity," Savran said. "Our platform's ability to work with whole unprocessed blood is highly scalable to meet the high demand that we foresee in the future." Â