NEW YORK (360Dx) – Glympse Bio is developing a testing platform that uses sensors inside the body along with measurements in urine for a broad range of disease detection and monitoring applications.
The Massachusetts Institute of Technology spinout, now emerging from stealth mode, has "created a new class of activity sensors that go in and query the body and report back clinically relevant information," the firm's newly appointed CEO Caroline Loew said in an interview. The technology "is designed to be part of a safe, simple, fast, noninvasive test that provides detailed insights into disease activity in real time and provide information about onset, stage of disease, and response to treatment," she added.
The firm is conducting its first clinical trial to validate the platform in patients with nonalcoholic steatohepatitis (NASH), a main cause of liver fibrosis, which can lead to cirrhosis and cancer.
However, diagnosing NASH would only be the tip of the iceberg if the firm's plans come to fruition, Loew said. Glympse Bio said it has internally validated its technology in 10 different diseases using multiple sensor delivery methods and a broad range of analytical readouts. Its researchers are developing the platform for several medical applications, including the detection of cancers, immune conditions, and infectious diseases such as pneumonia, in addition to liver fibrosis.
The platform works in the following manner: Upon injection into a patient, nanoparticle sensors move to the disease site, interrogate the biological activity of diseased tissue, and then emit a signal that can be detected from the patient's urine. Disease sites are aligned to customizing routes of delivery, including intravenous, inhaled, and subcutaneous, and the platform is being designed to produce readouts that are compatible with a range of multiplexed analytical platforms including mass spectrometry and ELISAs.
Glympse Bio said it is applying machine learning algorithms to develop a proprietary, whole-genome database of enzymes and sensors capable of targeting all clinically relevant proteases, and that its platform is also extendable to multifunctional enzymes including kinases, glycases, and lipases.
Glympse Bio has created a "very clever platform" in which nanoparticles with a biocompatible polyethylene glycol core are affixed to specific peptides that have tags that can be detected by mass spectrometry, Scott Friedman, chief of the division of liver diseases at the Icahn School of Medicine at Mount Sinai, who is also a consultant with Glympse Bio and other diagnostic industry companies, said in an interview.
The peptides have different protein sequences that are specific for different proteases, he said, and in a clinical application, physicians would administer the sensors and the platform would measure the breakdown products in urine from the proteolysis of the nanoparticles. In animal studies, the researchers have shown that "you can assess the breakdown products qualitatively to great sensitivity and yield a map of which enzymes are going up and which enzymes are going down," he said.
Friedman said that the MIT spinout is developing its platform "to an extremely high standard" and that the test in animal studies has demonstrated an "incredible correlation both with the amount of expression of proteases in the tissue and with the stage of disease, which they are working to validate in humans."
Glympse Bio was spun out of the laboratory of MIT bioengineer Sangeeta Bhatia in 2015. It is located at LabCentral, a shared laboratory facility in Cambridge, Massachusetts.
The firm raised $6.6 million in a seed funding round in 2015. In October it announced that it had raised a further $22 million in a Series A financing round led by Venture Capital firms LS Polaris Innovation Fund and Arch Ventures.
The company said that the new funding will be directed at clinical trials for its technology platform with an initial application for NASH detection. The firm has completed preclinical testing for the NASH diagnostic, and it is pursuing a drug-device combination pathway in validating its platform and seeking US Food and Drug Administration approval. The firm anticipates pursuing getting reimbursements for its tests subsequent to receiving FDA approval, and its development pathway will ensure that it has the "appropriate data to support that," Loew said.
"We are coming out of stealth mode, but we have some very strong early data that leads us to believe that we have a technology that's going to have a big impact," Loew said. "We are not just a diagnostics company, and that contributes to the value and differentiation that the company can bring," she said, adding that Glimpse Bio's development pathway should enable it "to get rapidly into the market" using short and inexpensive clinical trials. The firm is in contact with the FDA regarding obtaining regulatory approval, but it is too early to report expectations for the timing of clearance, Loew said, adding it is also too early for the firm to provide a perspective on pricing of its platform and tests.
She said that the company has not yet focused in on who the would be target customers for the platform and tests but Glympse Bio is developing it so that it "becomes broadly available to diagnose and manage patients with disease."
In recent studies, researchers at Bhatia's lab at MIT have shown that the technology can be used to detect different types of cancers, including very small ovarian tumors, which could enable earlier diagnosis of ovarian cancer.
In their work to detect pneumonia, the researchers began by exploring the possibility of diagnosing infection by detecting proteases that are produced by microbes. They worked on detecting Pseudomonas aeruginosa, a common cause of hospital-acquired infections. Pseudomonas expresses a protease called LasA, so the researchers designed nanoparticles with peptides that can be cleaved by LasA.
The researchers also developed a second nanoparticle-based sensor that can monitor the host's immune response to infection. These nanoparticles are covered in peptides that are cleaved by a type of protease called elastase, which is produced by neutrophil immune cells.
In infectious diseases, the group is exploring differentiating between different pathogens, Colin Buss, a graduate student and researcher in Bhatia's MIT lab, who is not employed by Glympse Bio, said in an interview. In some patients with pneumonia, a chest X-ray may show inflammation because neutrophils are still active even if an antibiotic clears out the bacteria causing the infection. Using these two sensors together could reveal whether an antibiotic has cleared the infection despite inflammation still showing on a chest X-ray.
Buss is one of the lead authors of a study published in EBioMedicine, which he said "showed that the sensors could be responsive to both the bacteria causing the infection as well as the body's immune response to it," so you could monitor the disease state from both perspectives.
For this study, the researchers delivered the nanoparticles intravenously, but they are now working on a powdered version that could be inhaled. By inhaling a formulation, "you can very specifically target only the lung tissue to give you a better picture of what's happening," Buss said. "Obviously, that wouldn't work with other diseases that we are looking into such as liver disease and cancers.” With the inhalable option, the platform readout would be done by measuring the breath or urine, he said.
He said that injection or inhalation of nanoparticles has been raised by some scientists as a potential concern, but the group has implemented measures to make the sensors safe within the body. The polyethylene glycol nanoparticle core is biocompatible, breaks down into biocompatible biproducts, and is already in use in pharmaceutical products, he said.
"Potential issues that we do think about are things like immune recognition of the sensors we've designed," he said. "So far we've seen nothing of concern in our animal models, but we are keeping this in mind as we design the sensors and test them further."
He said that in animal models, the researchers were able to detect effective versus ineffective antibiotics within a few hours. The group was able to "very sensitively detect these conditions," he said. He acknowledged, though, that animal models don't perfectly match human disease, and the same levels of sensitivity may not be seen in humans.
Pneumonia and NASH
Pneumonia, which can be viral or bacterial, kills about 50,000 people in the US every year, and it can take more time than is desirable to identify the type of bacteria causing pneumonia and to choose the best antibiotic to treat it.
Further, NASH impacts about 100 million people worldwide, according to Glympse Bio. The firm anticipates that its technology will enable patients to adopt lifestyle changes that can impact the disease when it is in its earlier stages. It could also help clinicians modulate the therapeutics that can prevent disease progression once they become available.
NASH, an accumulation of liver fat, is concerning for clinicians and patients because it "is almost always associated with other markers of the metabolic syndrome, which include obesity, hyperlipidemia, hypertension, and type 2 diabetes," Friedman said.
Inflammation and scaring can progress and increase the risk of cirrhosis and liver cancer, he said, adding that recognizing an unmet need to effectively treat patients, both pharma and biotech companies are scrambling to develop drugs for the condition.
"There has been almost a stampede to develop drugs to treat this," he said. Four drugs are in Phase III trials, about 20 are in Phase II, and more than 50 are in Phase I, he said.
"The challenge is that the disease can only be diagnosed definitively by liver biopsy, which is very invasive, and captures a very small fraction of the overall organ," he said. "Because it is invasive if you are doing a drug trial or if you are trying to diagnose the disease, [in most circumstances] you can't do more than one or two biopsies."
Effective diagnostic tests are needed, he said, to ascertain whether a patient has a condition that clinicians can monitor but not treat, or has NASH "and requires more careful monitoring and, potentially, consideration for a clinical trial. The challenge is how can we ultimately get information that tells us whether a patient has NASH, what stage they are at, and whether they are responding to a drug without having to do a biopsy."
Friedman said that Glympse Bio's test is likely to be among several diagnostic tests to emerge in the market to diagnose NASH. However, the firm is developing a "unique, highly quantitative reproducible test that looks like it holds great promise in assessing response to therapies and has already been embraced by at least one major pharmaceutical company in their clinical trial."
Glympse Bio declined to disclose the name of the pharma company.
"Obviously, the story has yet to be fully written, and the platform needs to be validated in human disease, but I am big fan because of the novelty and underlying science and the quality of the data that they have generated," Friedman said.