NEW YORK (360Dx) – Chalmers University of Technology spinout Elypta is developing a metabolism-based liquid biopsy platform for detection and monitoring of cancers, including early detection of recurrent renal cell carcinoma (RCC) after surgery.
Elypta is advancing research, that originated at Chalmers in Gothenburg, Sweden, into the use of glycosaminoglycan metabolites as diagnostic biomarkers for a range of cancer diagnostic applications, the firm's CEO Karl Bergman said in an interview.
Its platform measures up to 19 glycosaminoglycan metabolites in serum and urine and uses an algorithm-based scoring system, called the GAG score, named after its class of metabolites.
Earlier this week, the firm announced that the European Union's Horizon 2020 program has awarded it a €2.4 million ($2.7 million) grant for small- and medium-sized enterprises. The Stockholm, Sweden-based firm anticipates funding a multicenter prospective trial with between 200 and 300 patient samples aimed at validating its platform for early detection of recurrent RCC, the most common form of kidney cancer.
Its method involves measuring a panel of metabolites whose composition has been found to be altered in the blood and urine of cancer patients, allowing identification of distinct signatures using machine learning.
Bergman said that the metabolism-based approach using easily collected blood or urine samples allows for a safe and highly sensitive test that is ideal for close follow-up of cancer patients.
The firm anticipates obtaining CE-marking and launching a clinical trial for RCC detection in 2020, Bergman said.
During the next few years, it will build out its commercial organization, including establishing a sales and marketing team, and it anticipates partnering with clinical diagnostic labs around the world to which it will deliver diagnostic kits that use its glycosaminoglycan biomarker kit for detection and cloud-based machine learning software to analyze test results.
The firm's approach to sales and marketing will differ from region to region, and it could collaborate with marketing and distribution partner companies to sell to urologists, Bergman said.
Elypta, which has plans to eventually develop several cancer-related diagnostic tests based on its platform, anticipates applying to the US Food and Drug Administration for clearance of its kit and software for post-surgery RCC detection in 2022.
To further support its commercial initiatives, the firm plans to initiate a Series A round of funding this year and anticipates obtaining between €6 million and €10 million, Bergman said.
In the coming years, Elypta plans to initiate additional trials for cancer indications other than RCC, but it is too early to disclose details about those indications, he said.
"We are trying to determine if blood and urine samples taken as a follow-up for patients that have been treated for localized RCC works as well as or better than the imaging that we currently use for follow-up of these patients," Saeed Dabestani, a urologic surgeon from Lund University and senior associate of the European Association of Urology Guidelines Panel for Renal Cell Carcinoma, said in an interview.
Dabestani, a medical advisor to Elypta and the primary investigator for the clinical trial, noted that more than 400,000 people are diagnosed with RCC each year. Of the 70 to 80 percent of RCC patients eligible for surgery undertaken with the intent to cure them about 20 percent will suffer from recurrent cancer within five years.
About half of those recurrences happen within the first two years following surgery.
The gold standard for follow-up to detect recurrences is medical imaging, usually computed tomography scans, taken at regular intervals. About 30 percent of recurrences are found outside these follow-up protocols, and currently there is often little chance of curative treatment at the time recurrence is detected, Dabestani said.
Imaging usually doesn't enable follow-up testing frequently enough for it to be most effective and enable appropriate early detection, he said, because of its cost and the danger to patients of administering too many radiation dosages.
Statistics show that when RCC recurs in patients in about two years after surgery, the disease has usually metastasized because its tumors are already so aggressive at this time, Dabestani said.
"The more frequently you can follow up with the patient, the higher is the likelihood of catching an earlier recurrence," and detecting an early recurrence enables implementing curative treatments and/or the potential to prolong life, he said.
The objective of Elypta's planned clinical trial is to show that use of the metabolism-based liquid biopsy platform is an effective way to detect a recurrence before metastasis is visible by imaging, which is normally used during follow-up to surgery.
"We believe that this will be the case and if we can prove it, then we have a novel way to follow up on these patients used as a standalone kit or in combination with imaging," which would be implemented as needed to validate a positive test result, Dabestani said.
For the clinical trial, Elypta is in discussions with more than 10 academic health centers. In the US, it anticipates collaborating with MD Anderson Cancer Center in Houston, Memorial Sloan Kettering Cancer Center in New York, and Emory University in Atlanta. In Europe, the firm is in discussion with Addenbrooke's Hospital in Cambridge, UK; Royal Free Hospital in London; Haukeland University Hospital in Bergen, Norway; and San Raffaele Hospital in Milan, Italy.
"These are academic hospitals that understand the complexity of why it's difficult to do a proper follow-up in a way that makes sense for RCC patients," Dabestani said.
Dabestani joined Elypta as a medical advisor after meeting Francesco Gatto, a scientist in the department of biology and biological engineering at Chalmers University of Technology, and whose research became a foundation of the company's technology.
Prior to cofounding Elypta and becoming its chief scientific officer, Gatto spent several years modeling cancer metabolism using genome-scale metabolic networks and omics data mining at Chalmers and as a visiting scholar at University of California, San Diego.
In 2016, Gatto and his colleagues published a study in Cell Reports in which they conducted genome-scale metabolic modeling to uncover metabolic reprogramming in 481 clear cell renal cell carcinoma samples, and they found strongly coordinated regulation of glycosaminoglycan biosynthesis at the transcript and protein levels.
They were encouraged, Bergman said, by the validation of glycosaminoglycan scores that distinguished metastatic RCC patients with between 93.1 percent and 100 percent accuracy.
That study produced "the first clear signal of the potential" to use glycosaminoglycans as diagnostic markers, Bergman said.
Researchers at MSKCC subsequently collaborated with the Chalmers University researchers to validate a proof-of-concept assay and establish its diagnostic potential. They published the results of their study in the journal European Urology Oncology.
The researchers demonstrated a 93.5 percent level of sensitivity for detection of all stages of RCC, and that study highlighted the true potential for the assay, Bergman said.
"Importantly, the proof-of-concept study with MSKCC showed that we can detect stage I RCC with very high sensitivity," he said. Early diagnosis prior to surgery "is not our first clinical application but it is a natural progression for us within RCC and indeed other cancers," Bergman said.
From pilot studies and preclinical work, the GAG score could potentially be used for early detection of several cancers, he said.
As for RCC detection, the investigators believe that there are a few distinct uses. In addition to the post-surgery indication, they are investigating using the test to track the progression of patients who are being treated for kidney cancer. A lower GAG score could indicate that a patient is responding to therapy. The investigators also believe that the test could be used to help clinicians evaluate a patient's prognosis following detection.
The firm has used its platform to investigate more than 10 cancers in retrospective studies and it sees "great potential in all of them," Bergman said. The firm has plans to introduce a research-use-only tool that clinicians could use in conducting kidney cancer research, he said.