NEW YORK (360Dx) – Glycomics startup AccuDava is preparing a clinical study for its glycan-based test for predicting patient response to first-line platinum-based chemotherapy in ovarian cancer.
According to Nahid Razi, AccuDava’s founder and CEO, the company is collaborating with the Fred Hutchinson Cancer Research Center (FHCRC) to obtain clinical samples for a study it hopes to complete later this year.
La Jolla, California-based AccuDava last month received $50,000 in funding from the National Cancer Institute, which Razi said it will use to help fund the study and other company activities. The company was also recently selected to participate in the National Institutes of Health’s Innovation Corps (I-Corps) program, which is intended to support and accelerate the translation of clinical products by providing firms with access to industry expertise and potential customers.
AccuDava also received a $297,480 NCI grant in 2017.
Founded by Razi in 2006, AccuDava’s focus is identifying glycan markers for predicting patient response to chemotherapy. Razi started the firm as an independent project while working as director of the glycan-microarray facility at The Scripps Research Institute. The company, which has three full-time employees along with several outside consultants, has been a modest affair for much of its existence, with Razi funding much of its efforts with her own money. However, between the recent NCI awards and its planned clinical study, the firm is expanding its ambitions.
Razi's interest in the potential of glycans to serve as markers of drug efficacy was inspired by the case of a friend who suffered from a chemotherapy-resistant cancer, she said. "That made me begin thinking about using glycobiology to help detect resistance before administering [chemotherapy]."
"I formed the company mainly because I wanted to be an independent entity [separate from TSRI] as I worked on this project," Razi said. "I sublet a small [lab] bench and worked on it on the weekends just as a side project. I didn't really know if it would work, but, fortunately, it worked well."
Razi began working on AccuDava full time in 2012 after NIH funding ended for the Consortium for Functional Glycomics, the organization that housed her glycan microarray work at TSRI.
While her TSRI work focused on glycan microarrays, Razi used fluorescence-activated cell sorting for her discovery work at AccuDava. Analyzing ovarian cancer cell lines with different drug resistance profiles, she identified two glycans that were present in higher levels in chemotherapy-sensitive cells and in lower levels in resistant cells.
Glycans are sugar molecules that are attached to a wide variety of molecules and can play important roles in modifying the functions of these molecules. Glycobiology is a major area of interest in cancer biology and research into cancer biomarkers and, in fact, the majority of cancer protein markers currently in clinical use are glycol-proteins.
Razi said that she has not determined to what molecules in the cell the two glycans she tests for are attached, but she believed they were most likely carried by proteins. Identifying the specific proteins they modify is an active area of investigation for the company and, Razi said, "a very important part of this study."
She said that she believes these glycans are carried by glycoproteins that are within the cell membrane and that are involved in drug internalization in some manner.
"I have been trying to pursue that question as much as I can with the limited funding that I have," she said.
However, Razi noted, for the purposes of the chemotherapy response test, "it is enough to monitor or measure the amounts of these glycan motifs" without identifying the molecules they are attached to.
In a retrospective study looking at 27 ovarian cancer samples collected before chemotherapy treatment, the glycan markers — termed glycomarker 1 and glycomarker 2 — predicted response to chemotherapy in 25 of 27 (92 percent) and 19 of 27 (70 percent) samples, respectively.
While encouraging, the study size was too small to provide statistical significant, Razi noted. AccuDava is now planning a 140-patient study to validate these results and establish clinical cut points for each of the glycomarkers. Upon completion of the study, the company hopes to launch the assay as a laboratory-developed test, Razi said, while continuing to collect additional data to support an eventual US Food & Drug Administration submission.
The company initially hoped to complete the study, which it is undertaking in collaboration with clinicians at the FHCRC, by the end of July, but Razi said that date could be pushed back slightly due to its acceptance into the NIH I-Corps program. That program begins in mid-April and lasts eight weeks, she said.
The glycomarkers can be tested for using established immunohistochemistry methods, Razi said, noting that this could help it fit within existing pathology workflows. Ultimately, the goal is to develop the test as a kit that could be performed in any clinical laboratory doing cancer pathology.
"The test could be done on the same series of tissue slides they would [typically] prepare," she said. "And it would say whether a patient should go to the first-line chemotherapy, or if they should move directly to a second-line option."
Ovarian cancer is a relatively sensitive sold tumor in terms of initial response to chemotherapy (though a large percentage of patients will later develop resistance). Even so, some 20 percent to 40 percent of patients will not respond to first-line chemotherapy.
However, Razi said, "there is no direct test that predicts this resistance. So patients have to go through chemotherapy, and then only after several rounds of chemotherapy is it revealed if they are responsive or not."
The AccuDava test aims to let patients skip chemotherapy when it is likely to be ineffective, allowing them to move on to other available treatments and better preserving their quality of life, Razi said.
She noted that while ovarian cancer is the company's initial focus, it has data indicating the markers could be useful for predicting the effectiveness of platinum-based chemotherapy in other cancer types, as well.