NEW YORK (GenomeWeb) – Using ex vivo 3D (EV-3D) cell culture technology to model and predict a patient's therapeutic response to drugs, startup Kiyatec expects to target the oncology market with ovarian cancer and glioblastoma assays in 2022.
While Kiyatec currently offers a drug discovery service for pharmaceutical partners, the firm is working toward commercializing a clinical service for oncologists, and has begun a validation study for this application.
Kiyatec's cell-based assays model and predict a patient's therapeutic response to drugs in order to drive potential drug development for a variety of different cancers.
A spinout of Clemson University's bioengineering department, the Greenville, South Carolina-based firm relocated to Prisma Health's Institute for Translational Oncology Research in 2011. According to Kiyatec Cofounder and CEO Matt Gevaert, the firm then expanded through several contracts and grants from the National Cancer Institute. The NCI has awarded the firm a total of about $4 million in contracts since 2013 to develop versions of its 3D cancer cell culture models.
After operating on a patient during surgery, an oncologist collects cancer tissue and mails it off to Kiyatec's CLIA-certified lab in a customized validation specimen transport kit that can preserve tissue beyond 18 to 24 hours.
Once the sample arrives, Gevaert said that his team breaks the tumor into individual cells and then reconstructs it into several, independent living 3D models. In the EV-3D assay, the group measures cell death as a consequence of drug concentration and normalize the results to untreated controls.
"Many other approaches rely on measuring many inputs, which adds cost and typically time," Gevaert said. "We are getting excellent results from this one parameter which, I believe, speaks to our high fidelity to human biology."
In order to ensure a high fidelity, Gevaert said that his team selects the drug prior to testing. The researchers monitor the results across a range of concentrations to provide important context of how that patient's tissue responds.
Provided that researchers have enough viable cells, Kiyatec normally tests between 8 and 12 drugs per patient sample it receives.
"The drugs tested are specific for each indication, i.e. ovarian cancer panel drugs are different than a glioblastoma multiforme panel," Gevaert said. "By engineering the geospatial relationships, you can build the replicate through engineering principles, instead of what's coming out of the body."
Kiyatec aim to address two major questions regarding commercial drug discovery when working with pharmaceutical companies. First, the group examines the utility of drugs that have yet to be used in the clinical setting. He noted that pharmaceutical companies have contracted Kiyatec to help develop models and use of primary cells to better understand the response behavior of to their drugs before advancing them to clinical trials. In addition, Kiyatec helps the firm determine which drugs to actively pursue in clinical trials.
"[Pharma/biotech companies] are leveraging our models to strengthen their preclinical development programs, commonly but not exclusively to make decisions on which candidates to advance in their preclinical pipelines," Gevaert explained.
According to Gevaert, Kiyatec also tests drugs that are currently clinically useful right now and involved in patient care.
"If a person has a particular cancer, there are drugs today that are associated with standard of care," Gevaert noted. "Our model accommodates all kinds of drugs of the broad classes that are out there."
Gevaert said that his team can deliver a response profile of the cancer to the tested drugs to customers in about seven days.
In addition to collaborating with pharmaceutical partners on drug discovery, Kiyatec is also moving toward the clinical oncology space with its EV-3D assay.
In 2018, the firm launched a prospective study called "3D-Predict" to validate the EV-3D assay for drug response using a patient's own biopsy or resected tumor tissue for examining response to therapy for advanced cancers. Gevaert's team aims to validate the predictive accuracy of the assay and correlate response predictions to clinical outcomes among patients with newly diagnosed ovarian cancer, glioblastoma, and certain rare tumors.
In the study, the researchers are initially focusing on tumor types that have been analytically validated with the assay. The team will then collect data on a limited number of the different cancer types.
Gevaert anticipates that the validation study will last until 2022, with initial publications out in 2021. The team aims to enroll a total of 570 cancer patients undergoing surgery or biopsy. As part of the study, Kiyatec is partnering with several different academic groups, including Roswell Park Comprehensive Cancer Center, Oregon Health and Science University, Prisma Health (formerly Palmetto Health and Greenville Health System), and Inova Fairfax Hospital.
Earlier this month, Kiyatec raised $3 million in a Series B2 funding round to fund the 3D-Predict study, with VentureSouth and LabCorp. Gevaert noted that future round C funding will finance "go-to-market and clinical revenue acceleration" to improve existing revenue.
Going forward, Kiyatec aims to collaborate with LabCorp's Covance drug development business.
Gevaert highlighted that Kiyatec has been working with Genentech but declined to comment further on the partnership.
According to Gevaert, Kiyatec has encountered logistical challenges while developing and attempting to validate its EV-3D technology. In order to minimize tissue degradation after surgery and preserve the sample during delivery, the team developed a customized, validated specimen transport kit that Gevaert said can maintain tissue viability up to five days.
In addition, Gevaert noted that clinical sites can use a web portal to create shipping labels, which immediately notifies Kiyatec that the specimen is on its way. The firm also works with commercial courier and transport services to ensure rapid delivery from the clinic to its lab.
In order to establish its commercial presence, Kiyatec has also begun to engage groups both in and outside the clinical space, which has been aided by its colocation with the Institute for Translational Oncology Research.
"Being located inside a big clinical cancer treatment center enhanced our development of key capabilities like working with cancer cells coming directly from patients through surgery or biopsies," Gevaert said. "Clinical cancer care is very complex, so it's a big deal to be able to develop that understanding from the inside and then be able to use that understanding to develop our tests."
According to Gevaert, the team has received several patents for the 3D cellular technology, both with the US Patent and Trademark Office and abroad. Gevaert said that the firm wants to apply the tool to drugs through their entire life cycle, "from preclinical considerations in testing to trials informing drug selection as clinical care.".
Kiyatec hopes to eventually apply the EV-3D assay in the precision oncology space. Gevaert explained that most groups are not measuring the patient's interaction with the targeted drug.
"In the previous paradigm, you're sequencing the patient's DNA, but there's no interaction that you're characterizing," Gevaert said. "What we do is take that one step further and measuring what happens when you expose that person's live cells to drugs."
Gevaert therefore argues that the firm's technology takes personalized medicine to a new level of personalization or individualization. Instead of collecting a statistic on what patients have a shared mutation, the team can measure data on how the individual's personal cells react in response to the standard-of-care cancer drug agents. He also noted that the firm's assay examines several concentrations of tumor cells, while some approaches only test at only a single concentration
"Within the engineering side, we stand out because of our ability to use primary live tissue, which is historically not a proficiency of other groups," Gevaert said. "In addition, we've done the hard work to provide scalability and quality controls."
Gevaert said that Kiyatec expects to commercialize the 3D cell culture technology for the clinical oncology space based on the 3D-Predict trial's results. The team aims to develop a clinical assay for patient response during treatment for ovarian cancer and glioblastomas, followed by a similar assay that Gevaert believes can "add some value for patients that have solid tumors that are clinically rare."
However, Gevaert declined to comment on whether the firm will offer the assay as a lab-developed test out of its CLIA lab or aim for full US Food and Drug 510(k) approval.
Because Kiyatec is developing a suite of clinical tests for multiple cancer indications, Gevaert said the firm has yet to determine an exact price for the testing service. However, he believes that the firm will price the service based on its value to improving patient outcomes and the emerging competitive landscape.
In general, Gevaert emphasized the team's overall goal is to generate high-quality data in the trial that will demonstrate that the using the EV-3D assay will lead to better outcomes. The group will then address questions around clinical utility.
"Hopefully, as the trial unfolds, we'll be able to demonstrate that we have material value by bringing this kind of new personalized, individualized information that comes from measuring the interaction of drug with live cells," Gevaert said.