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Axim Aims to Commercialize Sapphire BioTech's Antibody-Based Cancer Assays as Companion Diagnostics

NEW YORK – Axim Biotechnologies plans to use an assay developed by recently acquired Sapphire Biotech as a companion diagnostic for drugs in development that inhibit  quiescin sulfydryl oxidase 1 (QSOX1), a tumor-derived enzyme involved in metastasis. 

Initially, San Diego-based Axim expects to launch it as a tissue-based, immunohistochemistry test in mid-2021. By early 2022, the company, which is also developing analogs to a drug it has licensed from Arizona State University, expects to market a dipstick version of the assay using plasma samples.

Launched in 2019, Sapphire's core technology stems from cancer research at ASU conducted by Douglas Faigel, chair of the gastroenterology and hepatology department at Mayo Clinic, and Douglas Lake, a professor at ASU. Lake cofounded Sapphire with Chief Scientific Officer Sergei Svarovsky and CEO Catalina Valencia.  

After initially discovering that QSOX1 is overexpressed during pancreatic cancer tumorigenesis in 2008, Lake's team has since found that the biomarker is also important during tumor cell invasion, facilitating tumor cell migration at the tumor-stroma interface. The group believes QSOX1 could also act as a prognostic marker of a tumor's metastatic potential, predict a patient's risk of relapse, serve as an initial biomarker for the presence of cancer, and be a potential therapeutic target for treating different cancers.

Using Lake's research at ASU, Sapphire began developing a prototype that detects the presence of QSOX1. In addition to validating the antibody-based test on different cancer types, such as bladder cancer,  Sapphire obtained an exclusive license from SkySong Innovations — the licensing agent for ASU — to develop therapeutic applications for QSOX1 small molecular inhibitors.

Axim CEO John Huemoeller said that the firm acquired Sapphire in January to pivot away from the cannabis market, where it had been watching its stock price gradually dwindle since launching as a public company in 2014. He said Axim hopes to enter both the point-of-care space by commercializing the QSOX1 tests that Sapphire's is developing, as well as the oncology market by developing therapeutics targeting QSOX1.

Huemoeller said that Axim acquired Sapphire for 54 million of Axim's shares, but declined to disclose the price of the deal. In buying Sapphire, Axim saw a rich opportunity in a growing market.

"The size of the oncology drug market is expected to hit $157 billion in five years, and the cancer diagnostic market is even larger," Huemoeller said. "Companies that have small molecular [and/or] companion diagnostics have much higher valuations, and we have both."

As part of the acquisition, Axim has opened a new lab in San Diego to help the research team and moved its corporate office there from New York, as well.  

The plan is to first develop a tissue-based version of the QSOX1 test to help determine the stage of a patient's cancer. Samples for the test will be collected via a fine needle aspirate. After examining multiple tumor types, Lake said the firm will determine which one is most appropriate for the immunohistochemistry test.  

Eventually, Axim plans to offer QSOX1-based tests in a lateral flow format for use as a rapid diagnostic test (RDT) using plasma samples. Comparing it to a pregnancy dipstick test, Lake said that QSOX1 in the patient's sample would bind to a gold nanoparticle-antibody conjugate and to proprietary antibodies — developed by Sapphire's and Lake's laboratories — to provide a signal. The signal intensity is directly proportional to the amount of an analyte, such as QSOX1, in the plasma sample.

"Finding the right pair of antibodies for the sandwich assay was the main hurdle," Lake said, noting his team screened "at least 15 antibodies in different configurations to arrive at the final design." 

Valencia said that the RDT requires about 5 to 7 ml of a patient's plasma and that the test could potentially provide actionable results within 10 to 15 minutes, in contrast to the immunohistochemistry test, which would take "hours to complete" and can only be done in a lab.

Lake said that an RDT version of the QSOX1 test could be used in combination with imaging when a biopsy is not warranted or when a biopsy poses undue risk to the patient. On the other hand, Svarovsky explained that while the RDT measures levels of QSOX1 in the bloodstream indicating that a cancer is present, it cannot pinpoint the exact origin without additional biomarkers. He noted that the immunohistochemistry test, therefore, addresses the need for specific profiling of cancer tissue removed during biopsy.

Svarovsky added that the primary application of the CDx assays will be to monitor response to the firm's small molecule drug candidates shown to suppress tumor growth through deactivation of the QSOX1 enzyme. Highlighting that QSOX1 is a general hallmark of cancer progression, Svarovsky said that the CDx tests could potentially be applicable to any cancer therapeutic.

Mayo collaboration

In February 2019, Sapphire launched a collaboration with the Mayo Clinic to examine 200 blood samples from bladder cancer patients for the presence of QSOX1 biomarkers using a version of its RDT assay. According to Valencia, the study's initial results are "very encouraging" and showed significantly elevated levels of QSOX1 over normal samples. 

Sapphire also launched a validation study with Faigel's team at Mayo in December 2019 to test the RDT prototype on pancreatic cancer cells. However, the COVID-19 pandemic has prevented the researchers from continuing with the study. So far, they have collected about 45 of the 60 samples they initially targeted, and the firm hopes to finish sample collection this summer and begin running samples on the lateral flow assay.

As part of the longitudinal pancreatic cancer study, the researchers aim to collect blood samples from patients before, during, and after cancer treatment to correlate QSOX1 levels with the cancer stage Valencia said. The team also aims to establish the test's clinical sensitivity and specificity in ongoing studies.

In addition to bladder and pancreatic cancer samples, Sapphire is validating the QSOX1 tests on breast cancer and glioblastoma samples, Lake said. The firm is currently performing in vitro and in vivo testing with Mayo; Translational Drug Development (TD2), an oncology contract research organization; and ASU to measure QSOX1 levels in mice tissue and blood samples.

"We've [also] obtained commercially available samples from firms such as BioIVT and from the San Diego Blood Bank, and we've tested those to identify the difference in QSOX1 levels," Valencia said.

Je-Yoel Cho, a veterinary biochemistry professor at Seoul National University in Seoul, South Korea, noted in an email that QSOX1 is a protein cross-linking enzyme highly expressed in lung cancer tissues. His team previously found that QSOX1 promotes lung cancer migration and invasion, acting as a rigid matrix that allows cancer cells to easily become metastasized.

Cho highlighted that QSOX1 can be advantageous for detecting metastasis because the level of the protein can be measured in several body fluids, including blood. At the same time, he acknowledged that the protein's level in blood is typically very low, and that a sensitive method is needed to measure it.

While Cho's team believes that QSOX1 could be used to indicate response to a drug, his team has not found any clear data to prove the theory. Despite being unaware of any firms currently pursuing QSOX1 as a companion diagnostic biomarker, Cho noted that he has seen around 10 other research papers and labs looking into QSOX1 as a cancer biomarker.

Regardless, after developing the technology further and validating it on larger cohorts of different cancer patients, Axim anticipates applying for 510(k) clearance from the US and Food Drug Administration for the tissue- and blood-based tests. For use of the tests as companion diagnostics, the firm would have to pursue an additional regulatory pathway for the tests.

Since multiple tumor types express QSOX1, Lake believes that any drug that decreases tumor burden "could enlist our diagnostic test."

Axim has not yet established a price for the QSOX1 tests.

Axim believes the QSOX1 tests could be used for recurrence monitoring and as a test for the early diagnosis of disease. Clinicians could integrate them as part of an early detection workflow in combination with other biomarkers representative of different cancers, such as CA-19-9 for pancreatic and gastrointestinal malignancies and prostate-specific antigen for prostate cancer.

Axim filed for a patent related to antibody-based tests for QSOX1 in February 2019 with the US Patent and Trademark Office. The firm has also filed six additional patents for therapeutic drug targets related to its QSOX1-inhibitor, SBI-183, which Sapphire licensed from SkySong as part of its push to develop drugs based on the antibody used in the QSOX1 tests.