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Biocept Eyes Neuro-Oncology for Future Liquid Biopsy Growth as Testing Lags Amid COVID Pandemic

NEW YORK – Liquid biopsy firm Biocept has seen its cancer testing activities significantly hamstrung over the last half-year as the COVID-19 pandemic has reduced demand for its suite of single-gene and multi-gene circulating tumor DNA assays and circulating tumor cell tests.

While some liquid biopsy companies have been able to continue to grow their customers base amid the challenges of the pandemic, Biocept's oncology testing revenue dropped significantly in both the second and third quarters of this year compared to the same period of 2019.

Despite this, the firm still believes it can compete in the non-invasive cancer testing market and is hoping as the pandemic eases that it will be able to cultivate adoption of its products and services in both existing and new areas.

According to Biocept's newly appointed Chief Medical Officer Michael Dugan, one important arm of this recovery is targeting the neuro-oncology space, which has become of particular interest to Biocept following the launch this January of a version of its Target Selector CTC isolation and ctDNA analyses for use on cerebral spinal fluid samples.

"We are particularly excited to develop [Target Selector CSF assays] for detecting lung and breast cancer that has metastasized to the brain or central nervous system," Dugan said during the call.

"Metastatic cancers frequently involve the central nervous system … sometimes as the only manifestation of the disease when it has been successfully treated in the rest of the body," he added. And although this spread of cancer to the central nervous system is usually associated with a worsening prognosis, many patients with metastases to the central nervous system are living significantly longer due to advances in treatment strategies and emerging targeted therapies.

As a result, Dugan argued, "There are many patients for whom timely confirmation of brain or spinal cord involvement and appropriate early treatment can lead to significantly better projected survival and marked reduction in neurologic symptoms such as headaches, impaired mobility or loss of vision."

Biocept is hoping that it can make a case for its technology as a tool to address an unmet need, arguing that the current gold standard for analyzing cerebral spinal fluid for evidence of CNS metastases, CSF cytology, has limited sensitivity and no ability to provide molecular information that might guide targeted therapy.

According to Dugan, the company believes its technology can allow "more sensitive cell-specific and quantitative assessment of tumors in CSF to gauge treatment response matched with information about molecular alterations that can aid physicians in choosing the most appropriate therapy. This can be a more clinically effective and cost-effective approach," he said.

Researchers have expanded efforts in recent years to bring liquid biopsy to brain tumors and brain metastases, with studies exploring numerous technologies and platforms, including cell-free or circulating tumor DNA analyses, CTC detection, and assays that isolate and profile extracellular vesicles.

The use of Biocept's platform in CNS tumors has been limited thus far, but the company claimed it expects to expand its efforts moving forward.

Researchers working with its technology presented an abstract at the American Society for Clinical Oncology's virtual annual meeting earlier this year, reporting on a study that compared Biocept's assays to standard-of-care cytology in detecting cancer material in CSF and identifying leptomeningeal metastases, which occur in the thin layers of tissue that cover and protect the brain and spinal cord.

Investigators collected CSF from a cohort of 14 patients with a prior solid tumor diagnosis (mostly breast cancer) who were suspicious for leptomeningeal metastases and used Biocept's CTC detection assay, which uses an antibody-based microfluidic device to isolate tumor cells, as well as next-generation sequencing of cell-free DNA to detect somatic mutations, comparing the results to standard CSF cytology.

The group concluded that based on high concordance between Biocept's tests and cytology results, the company’s technology is a "viable platform" for detection of breast cancer CTCs in CSF.

This October, other researchers presented results from another small study of the company's CSF assays at a liquid biopsy-focused meeting held by the International Association for the Study of Lung Cancer.

In that study, investigators analyzed 28 cerebrospinal fluid samples from 15 non-small cell lung cancer patients with metastases to the central nervous system obtained both before and during treatment. The patients were enrolled in a Phase II Multicenter Study of the drug tesevatinib in subjects with EGFR-activating mutations.

According to the authors, Biocept's Target Selector testing detected CTCs in 78 percent of the CSF samples, while conventional cytology only yielded a positive result in 55 percent. Target Selector testing also allowed identification of actionable EGFR mutations in the cerebrospinal fluid that could potentially inform treatment selection, the group reported.

A pivotal question for building a business for its technology in CSF tumors will be whether Biocept can establish that using its assays actually improves patients' care or outcomes compared to cytology — or, just as importantly, compared to the use of other liquid biopsy platforms.

Establishing not just technical validity but clinical utility has been an ongoing challenge for liquid biopsy approaches in brain cancer, according to leading researchers.

Biocept's IASLC presentation offered a brief hint of utility data, with investigators examining the possibility that CTC quantities and/or EGFR mutations in CSF might correlate with treatment response.

Investigators did see some signs that decreases in CTC density, as well as in EGFR Exon Deletion 19 copy number, correlated with partial responses of leptomeningeal metastases to treatment with tesevatinib. But, they stressed that the small size and retrospective structure of this analysis means the findings are still only suggestive.

Dugan said that early data like this as well as internal development work Biocept has conducted on other brain tumor applications, have "attracted the interest of many leading neuro-oncologists, thoracic oncologists and breast oncologists," some of whom are now working with the firm as "steady collaborators to better establish the clinical utility of our assays in this underserved area of oncology."

CSF testing currently represents less than 10 percent of Biocept's oncology volume, he added. But the firm is focused on developing new clinical studies and building awareness of its technology in the neuro-oncology space, expecting to see this niche gain volume over the next year.