NEW YORK (360Dx) – Todos Medical is developing low-cost spectroscopy tests that it intends to make broadly available to enable noninvasive screening for cancers.
Rather than looking for tumor cells or specific markers, the firm's Total Biochemical Infrared Analysis — which leverages Fourier transform infrared spectroscopy and a proprietary technique that analyzes spectrometer test results — would screen for solid tumors by measuring spectra representing biochemical changes in peripheral blood mononuclear cells, enabling the observation of a distinct immune response to breast, colorectal, lung, and other cancer types, Todos CEO Rami Zigdon said in an interview.
Test prototypes are in clinical testing, Todos said, adding its tests for breast and colorectal cancers are nearing commercial launch, and could be on the market in 2018 in Israel and parts of Asia, with a later launch planned in the US and Europe.
The firm is currently planning clinical trials for its breast and colorectal cancer tests, with a view to applying to the US Food and Drug Administration for clearance to market the platform and its assays in the US, Zigdon said. The timeline for a launch will depend on what the FDA will request from Todos as part of the review process.
Todos is evaluating the potential to provide a service that utilizes lab-developed tests from CLIA-certified laboratories, which would also enable access by clinicians in the US, he said.
Zigdon noted that to prioritize company resources, the firm will probably launch its breast cancer screening test in Asia and Israel prior to launching the colonoscopy screening test. However, it has not yet decided which test it would first launch in Europe and the US.
The company — established six years ago — uses core intellectual property developed at Ben-Gurion University in Israel.
"Our vision is to become the standard-of-care blood test for early cancer detection," Zigdon said, adding, "To achieve that vision, we have to be low cost, accurate, and accessible for the mass population."
According to Todos, its tests have demonstrated more than 80 percent sensitivity and specificity for both breast and colorectal cancer detection, and it is working to further validate these results.
The firm noted that it has embarked on clinical trials and has collected more than 1,000 individual blood samples that it is testing at medical centers in Israel, including the Wolfson Medical Center in Holon; Rabin Medical Center in Petach Tikva; Ichilov Medical Center in Tel Aviv; and elsewhere. The latest clinical trial for its breast cancer test included 59 patients and achieved 93 percent sensitivity and 87 percent specificity compared to routine mammography screening, the firm said.
The firm expects that accessibility of its cancer screening tests to the mass population will be enabled using FTIR spectrometers in testing laboratories, including hospital and reference labs. A Todos server would capture the spectrometer results, and the company's proprietary algorithm would analyze them. The firm would then make results available to physicians.
To offer the Todos test, laboratories would need to purchase an FTIR spectrometer, Zigdon said. Although the instrument is used broadly in analytical chemistry laboratories, clinical laboratories currently don't tend to use them, he added. The company is using a Bruker FTIR instrument, he said, but its goal is to find many potential vendors for the spectrometer.
Several FTIR spectrometer models can be purchased for less than $10,000.
"Measuring peripheral blood mononuclear cells is quite straightforward, and simplicity is one of the things we wanted to implement," Zigdon said.
Once the sample is received at a laboratory, it will be possible to process the test within a matter of hours, Zigdon said, adding that the overall time to result from a blood draw could occur within one day.
The first steps — from blood draw to providing the spectroscope measurement — would be done from any location in the world, and the final step prior to releasing a result — the analysis — would be "located on a centralized Todos Medical server," Zigdon said. After analysis, Todos would return the test result to a physician through an Internet portal.
"Our business model is straightforward and simple," he said, adding, "We sell a kit that consists of materials that enables the separation of blood" required for FTIR analysis. He said that the firm has not yet established a price for its kit, but that it should be as affordable to patients and providers as routine blood tests.
At the end of 2013, Todos received a CE mark for its test approach, and that enabled it to begin commercialization activities.
However, prior to launching the platform commercially, the firm needed to devote time to develop a test that can be used by the mass population, Zigdon said.
One of the firm's first tests takes aim at early detection of breast cancer. "We started by addressing an unmet need," Zigdon said. "Mammography is challenged to accurately detect breast cancer, and there are high rates of false positives and cases where patients are being sent for unneeded biopsies."
The Todos test would be implemented by clinicians as a supplementary tool to mammography, he noted.
In a paper published in the journal BMC Cancer, researchers at Todos wrote that conventional mammography is known to have a sensitivity of about 66 percent and specificity of about 92 percent. "However, recent studies show that screening with mammography does not reduce mortality," but it could lead to a 30 percent rate of overdiagnosis, and increase unnecessary surgical procedures and patient anxiety, they added.
In the study, the researchers isolated peripheral blood mononuclear cells and plasma, dried them on a zinc selenide slide, and then measured them under a Fourier transform infrared microscope to obtain their infrared absorption spectra.
"The idea here is to be able to help improve the specificity of breast cancer screening by using the Todos blood test," Meir Silver, the firm's vice president of clinical research and regulatory affairs, said in an interview, adding that "The goal with this is to reduce the number of biopsies that are required."
The FTIR test could also be useful to clinicians testing women at high risk for breast cancer because of detected genetic mutations, Zigdon said, adding that these patients currently go through repeated follow-up testing that's painful and expensive.
"We believe that we can help with this because some of the follow-up could be done with our blood test," Zigdon said. "Certain patients will need to undergo MRIs and more sophisticated screening tests, but overall, we can ease the testing burden."
Todos will face competition, however, and several commercial tests are already on the market for breast-cancer risk screening. In February, Cynvenio Biosysterms and Color announced an agreement to offer a combined version of their respective liquid biopsy and hereditary cancer tests, that analyzes alterations in the 30 genes on Color's hereditary cancer panel, as well as somatic cancer mutations in the 27 genes that Cynvenio's ClearID breast cancer test covers.
Earlier this month, Myriad Genetics launched riskScore, a new clinically validated precision medicine tool to enhance its myRisk Hereditary Cancer test. RiskScore quantifies a women’s risk of developing breast cancer by combining genetic markers throughout the genome with her family and clinical history.
Zigdon noted that a separate Todos assay, also blood-based, would enable screening for colorectal cancer and could "save the lives of a lot of people who hesitate or refuse to have a colonoscopy."
Compliance with taking standard-of-care colonoscopy tests is low, Zigdon said, adding "We can approach people who don't want to have a colonoscopy and give them a good tool to check for colon cancer at its early stages."
Such a test would compete with Exact Sciences' Cologuard, which uses stool DNA during noninvasive frontline screening tests for colorectal cancer in patients with average risk for the disease. Cologuard is FDA-approved and is covered by Medicare and an increasing number of commercial payors.
For all Todos assays, the steps of blood collection, blood separation, and spectral reading are similar from one type of cancer to another, Zigdon said. However, the firm generates new analytical algorithms that are specific to each disease area undergoing testing.
Additional tests for early detection of cancers, including an assay for lung cancer, are in the pipeline, and the firm is currently analyzing which tests it should develop subsequent to launching the breast screening and colorectal cancer tests. "The platform itself is capable of facilitating the generation of new tests quite fast and quite easily," Zigdon said, adding that a new test can be added in a year-and-a-half after the company has initiated its development.
The company has operated using funding from angel and private investors. To support its commercialization initiatives, the company has registered to be publicly traded with the OTCQB, an over-the-counter trading marketplace for small or early-stage companies.
Other researchers also see value in the use of FTIR for clinical testing. Researchers at the University of Central Lancashire, in Preston, UK, for example, recently reported that they have achieved accurate results using attenuated total reflection FTIR to identify Alzheimer's disease and other forms of dementia in patients' blood.
A commercial diagnostic test that uses the technique could be at least a few years away, and additional clinical testing would be needed prior to a launch, but such a test could eventually become a useful complement or alternative to existing tests for dementias, the UCLan researchers said.
Attenuated total reflection Fourier transform infrared spectroscopy of soft biological medium or body fluids, combined with appropriate data handling frameworks "is an attractive technique for rapid and reliable screening of multiple diseases," said Unil Perera, a professor of physics at Georgia State University.
In conjunction with the Institute for Biomedical Sciences at the university, Perera is using the technique to develop a minimally invasive, fingerpick-based blood test for use at a doctor’s office to screen for ulcerative colitis. Once the test gives an indication of colitis then a colonoscopy can be done, Perera said in an interview. He said that his group is ready to start human sample testing on a technique that he described with colleagues recently in a paper published in the Journal of Biophotonics.
Also, UK-based Glyconics, a spinout from Swansea University, is using Fourier transform infrared spectroscopy in point-of-care tests that it is developing for oncology, urology, and COPD diagnostics. FTIR analyzes sputum and identifies biomarkers for chronic obstructive pulmonary disease, and would allow for the differentiation of COPD from other respiratory ailments, the firm said.
Glyconics said that its technology could also provide a "very early" indication of exacerbating disease in patients with COPD, and that the technology analyzes many components of a sputum sample, including proteins, sugars, and nucleic acids.
The clinical trial results for Todos's CE-marked platform have been published in several peer-reviewed journals. However, it is not the only platform in development that uses noninvasive blood tests for the early detection of cancers based on the body's immunological response to malignancy.
In August, San Jose, California-based Itus said today it had renewed a collaborative agreement with the Wistar Institute for the development of its Cchek early cancer detection technology, which monitors changes in the immune response of individuals
Itus is using artificial intelligence and flow-cytometry analysis of immune cells from an individual's blood to identify patients with tumors.
The firm said it has demonstrated the efficacy of its technology in identifying 15 different types of tumors.
In May, when the International Association for the Study of Lung Cancer released the Atlas of PD-L1 Immunohistochemistry Testing in Lung Cancer, it stated that updates to its document will "almost certainly be needed, sooner rather than later," due to the rapidly evolving nature of the field, such as the investigation of biomarkers relating to the immune response.
HalioDx's Immunoscore platform, which looks at the immune response in diagnosing several cancers, is participating in new research projects that it hopes will result in new products that will benefit its business. The company is participating in two endeavors funded under France's €74.5 million ($89.3 million) Hospital-University Research in Health (RHU) program.
The company believes that its participation could result in multiple new tests based on its Immunoscore platform. The company said that it has a proof-of-concept on several cancers, including breast cancer and lung cancer.
In 2016, Novigenix published a multicenter clinical validation study of its blood test for early detection of colorectal cancer. Novigenix's assay, called Colox, combines a 29-gene host immune response panel with a pair of tumor-derived protein biomarkers to detect not only early-stage colorectal cancer, but also large adenomatous polyps that can be precursors to cancer.
Nicolas Demierre, director of business development at Novigenix, told 360Dx's sister publication GenomeWeb that the assay is used to select the right patients who have developed or are developing colorectal cancer, and then to enable follow-up with a diagnostic colonoscopy.
In the journal of Physical Chemistry and Biophysics, Shalmoli Bhattacharyya, a researcher in the Institute of Medical Education and Research in Chandigarh, India wrote that FTIR is rapidly gaining ground in modern clinical research. "Importantly, biological materials like proteins, carbohydrates, lipids, and nucleic acids have unique structures so it is possible to obtain spectral fingerprints corresponding to their functional groups," she said.
She noted that FTIR spectroscopic techniques generate an immediate appeal in the field of biology and medicine because of their fast and noninvasive nature.
The technique enables "easy visualization of cellular components based on their intrinsic properties and chemical composition, and provides a potential route to screen diagnostic markers for diseases like cancer," Bhattacharyya wrote.