NEW YORK (GenomeWeb) — Startup Cadex Genomics expects to soon launch a laboratory-developed test that uses a real-time quantitative PCR liquid biopsy assay with retrotransposon-based quantification technology to analyze the variable length of DNA fragments from cancer cells and provide clinicians with a tool to evaluate how cancer patients diagnosed with stage IV solid tumors are responding initially to treatment.
The test, a circulating tumor DNA assay called Alibrex, has so far shown a high positive predictive value — close to 100 percent — in preliminary clinical studies involving colorectal cancer patients, the firm's CEO Bill Haack said in an interview.
The firm expects to the launch test, which has a turnaround time of about 48 hours, at the beginning of next year, or even earlier. It can be used to provide results within two weeks of a patient receiving a cancer therapy, which is significantly faster than the three months needed to get results from CT imaging currently used by clinicians, Haack said.
In healthy individuals, the circulating tumor DNA fragments tend to be small and uniform in length, but in people with cancers these fragments vary in size in ways that the Alibrex test can detect and analyze, the firm said. The platform is being developed to differentiate normal cancer cells from circulating tumor DNA and measure the ratio of cancer DNA fragments correlating with early response to cancer therapy.
Clinicians would use a venous blood draw to assess whether the therapy is working within two weeks after a patient has started the regimen, allowing an oncologist to adjust the treatment, the firm said.
According to Scott Kopetz, a physician in the department of gastrointestinal medical oncology at MD Anderson Cancer Center, Alibrex can be used to test patient responses to cancer therapies regardless of the mutation or tumor type, providing "a lot of advantages in terms of ease of use and interpretation of results."
Kopetz led a preliminary clinical study at MD Anderson to test the clinical utility of the test. The MD Anderson study tested 40 patients who had received 47 different treatments because some received a second therapy.
In testing a patient's response to a cancer therapy, the assay "uses a very low volume of blood and fragmented DNA," and it is two- to tenfold less expensive than using NGS to monitor a patient's response, he said in an interview. The test demonstrated a specificity of 100 percent, meaning that all the patients identified by the test as not responding to a therapy were shown by imaging two to three months later to also have not responded.
"To make a call about treatment progression during the clinical study, the blood test needed to show that the patient really was progressing on imaging scans taken two to three months later," Kopetz said. "You want 100 percent specificity to feel highly confident that you can change the management of a patient's therapy."
Kopetz said that in standard treatment, clinicians use CT scanning to assess the response of patients on US Food and Drug Administration-approved therapies for colorectal cancer, such as regorafenib and Lonsur (trifluridine/tipiracil), two to three months following administration of the therapies.
About 25 percent of patients receiving the treatments obtain a clinical benefit, and all patients receiving the therapies are susceptible to toxicity and conditions such as fatigue, mouth sores, skin changes, and low blood counts that predispose them to severe infections, Kopetz said. The Alibrex test could be used to identify those patients who may not respond to such treatments, sparing them of the side effects and cost of treatments.
Kopetz noted that the goal is to replicate the pilot data obtained for the assay in additional settings and prospective studies and that MD Anderson could become one of the settings for the studies. Redwood City, California-based Cadex Genomics said it is preparing for such an international study that is expected to involve about 700 patient samples. Haack said the firm is in discussion to conduct the study with health centers in the US, Canada, and Israel.
The firm is developing assays to detect a patients' responses to therapies used to treat stage IV solid tumors not only in colorectal cancer, but also non-small cell lung cancer, he said. Later, Cadex anticipates launching an assay to monitor the response of patients to stage IV breast cancer treatments, but the anticipated timeline to launch is unclear.
The firm recently announced that it had raised $1.5 million in seed financing that it intends to use to expand clinical studies and further its business plan.
The firm, founded in 2018, expects to raise an additional $5 million in pre-Series A financing that will take it to the launch of its first assays for detecting response to therapies for non-small cell lung cancer and colorectal cancer and through additional clinical validation studies, Haack said.
Cadex Genomics said it also intends to use the funding to build a CLIA-certified clinical laboratory in an undisclosed location. Afterward, it also expects to initiate a Series A round to raise an additional $25 million to $35 million in funding later this year and to begin building out a global sales team.
Cadex Genomics' Chief Commercial Officer Greg Schafer said that the firm is in discussions with several potential co-marketing partners that have large oncology sales teams that would help it target international sales. "We are taking that approach because we want to drive adoption as quickly as possible," he said.
The company's technology at its current stage has been developed over more than 18 years by Sudhir Sinha, the firm's newly appointed chief scientific officer, and his colleagues at Tulane Medical School.
Sinha is also CEO of InnoGenomics Technologies, a developer of genetic tests for forensic scientists, and an adjunct professor of biochemistry and molecular biology at the Tulane University School of Medicine.
Cadex Genomics intends to soon apply multivariate analysis with machine learning to define cutoff values for its assays, Sinha said.
He has been working on the properties and utilities of Alu repeats and other retrotransposon, or variable length DNA fragments from cancer cells, including methods to use Alu for DNA quantification. As a result, he has developed methods to use these markers for cell free DNA concentration measurements in cancer patients' blood using multiplex qPCR.
The Cadex Genomics test provides a measurement of the total cfDNA concentration produced by cancer cells and normal cells present in the blood for two different fragment sizes.
The assay can also simultaneously quantitate nuclear DNA and mitochondrial DNA concentration in plasma, which could further enhance the predictability of the assay, Cadex Genomics said.
Cadex Genomics noted that a second preliminary clinical study to assess the validity of its assay conducted recently at Jewish General Hospital involved 79 patients. The assay demonstrated an area under the curve of 0.989, according to Cadex Genomics.
Haack said that the firm's validation studies are being designed to support its reimbursement strategy. The firm is planning meetings with the Centers for Medicare & Medicaid Services and private payors to understand their specific requirements for clinical studies to further demonstrate the test's clinical utility from the perspectives of patient outcomes and health economics. The firm is targeting obtaining reimbursement for its assays in Europe and Japan, as well as the US, he said.