NEW YORK ─ Massachusetts Institute of Technology spinout Glympse Bio is preparing to enter clinical studies to validate a nanosensor-based platform that measures dysregulated protease activity associated with liver disease, specific cancers, and infectious diseases.
With funding from a recently completed $46.7 million Series A financing, the Cambridge, Massachusetts-based company is initiating studies to detect patients' responses to treatments that are in development for nonalcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease. The platform will also be used to determine clinical trial participants’ stages of disease at initial screening.
Though there are no standard therapies for patients with NASH, many clinical studies are underway to develop them, and an activity-based sensor platform can help pharma companies bring drugs to market more quickly, Glympse Bio CEO Caroline Loew said in an interview.
The studies being initiated by Glympse with collaborators may lead to a premarket approval submission to the US Food and Drug Administration and ultimately enable the use of the company's technology as a prognostic and diagnostic tool for NASH, she said. However, the firm is not disclosing an anticipated timeline for the completion of the NASH-centered clinical studies or its FDA submission.
Glympse Bio said its activity-based nanosensors seek and find disease within the body and are later excreted in the urine for measurement by mass spectrometry and other detection methods.
"Our non-invasive technology detects real-time biological changes at the site of the disease using the activity-based sensors that we bioengineer and are tunable to any protease-mediated disease to improve care for patients across a number of therapeutic areas," Loew said.
Leveraging technology developed at MIT, Glympse Bio used machine-learning to develop a proprietary database of enzymes and sensors capable of targeting clinically relevant proteases that are specific to different medical conditions. The company tunes its sensors to be specific for each protease-mediated disease it targets.
Its bioengineered sensors consist of nanoparticles that are linked to substrates of proteases known to be dysregulated by specific disease processes. When the nanoparticles are introduced into the patient, the linked substrates are cleaved by target proteases, collected in the urine, and measured to assess the level of protease activity. Abnormal levels of activity indicate whether the patient has a specific medical condition, such as NASH, a type of cancer, or an infectious disease.
The firm uses intravenous delivery of the nanosensors for NASH and has developed proof-of-concept aerosol and subcutaneous delivery modalities that it anticipates deploying with its test for other conditions.
Protease activity detected by Glympse Bio's nanosensors are part and parcel of disease progression in many medical conditions, and the company has "the right test" for monitoring disease activity in NASH, said Mani Subramanian, who until March was senior vice president for liver diseases at Gilead Sciences.
"Any disease that involves inflammation and scaring reflects a dynamic process," and liver fibrosis is no exception, Subramanian said in an interview. "A test that can better quantify the magnitude of tissue remodeling as a result of protease enzymes makes good sense."
Subramanian, who is forming a company to develop therapies for NASH, noted that Foster City, California-based Gilead Sciences and Glympse Bio are in a strategic collaboration whereby the biopharma company is using the Glympse Bio platform to identify patients who may benefit from the drugs it is developing. Gilead, he said, invested in Glympse Bio's technology at the inception of its founding in 2015 by MIT bioengineer Sangeeta Bhatia.
When left untreated, NASH can lead to liver fibrosis and, in some cases, progress to liver cirrhosis and hepatocellular carcinoma. However, there are no approved therapies for the condition, and the current first line of treatment is lifestyle modifications including diet and exercise.
Gilead initially engaged with Glympse Bio in preclinical studies "to better understand the power of the platform and to use some of its own clinical datasets to link protease activity and liver disease with the activity probes," Subramanian said. "[The collaboration] has moved from evaluating a scientific concept to the development of a platform for use in Phase I drug studies where you get a sense of how to deliver the probes and get an accurate readout."
The Glympse Bio platform "could be very helpful to monitor the response to treatment for pretty much any drug that is being developed to treat NASH," of which there are many, he added.
Blood tests that are both available and in development accurately assess the severity of liver disease, but they provide a single snapshot of what is happening and have low clinical utility in monitoring ongoing disease activity, which is crucial to developing therapies, Subramanian said.
Among tests in development for liver disease, a team of European researchers announced last year that they are evaluating the use of a new blood test to diagnose non-alcoholic fatty liver disease in children.
Additionally, earlier this year, San Diego-based ProSciento announced a partnership with Herlev, Denmark-based Nordic Bioscience to identify blood-based translational biomarkers for nonalcoholic fatty liver disease and NASH.
Palo Alto, California-based DiscernDx recently acquired Newark, California-based Luminist Labs, a privately held developer of diagnostic technology for nonalcoholic steatohepatitis and other liver diseases.
Until now, however, most pharma firms have been trying to show efficacy in NASH treatments by using a liver biopsy as a baseline and then doing testing using the same approach a year and half later, Subramanian said. "In between, you don't know whether the drug is working, but with the Glympse Bio platform you can tease out whether the drug is working before you start seeing big changes in liver stiffness," he added.
Though needle biopsy is the definitive way to determine whether a patient has NASH, it is an uncomfortable procedure, Loew noted. "If you can persuade someone to have a needle biopsy [once], you may never get them to have it again," she said. "Needle biopsy doesn't lend itself to serial testing and can be inaccurate because it uses a small sample of the liver in the diagnosis of an inherently heterogenous disease."
The accuracy of results is further influenced, she added, by an analysis by a pathologist, which can be subjective and depend on that pathologist's level of experience.
Developing effective NASH treatments has proven elusive and the field has been marred recently by high-profile failures. Last year, for example, Gilead's selonsertib failed in its Phase III development program. Also, Lille, France-based Genfit said this May that its Phase III drug did not show statistical significance on the primary endpoint of NASH resolution without worsening of fibrosis, or on the key secondary endpoint of improvement in fibrosis.
In June, New York-based Intercept Pharmaceuticals announced that the FDA had issued a letter regarding its application for obeticholic acid for the treatment of fibrosis due to NASH, saying the predicted benefit of treatment remains uncertain and does not sufficiently outweigh the potential risks to support accelerated approval for the treatment of patients.
"It's a very complex market," Loew said. "But we may see the first therapeutics coming into the market in the next two to three years."
When new drugs are being developed, especially in the beginning, "enormous amounts of time and resources are being poured into determining whether there is a response to a new therapy," she said. "With real-time biological data, we can help companies speed up those activities."
Though its first commercial product is likely to be for NASH, Glympse Bio also has programs in oncology and infectious diseases, including for the detection and monitoring of lung cancer and potentially for the detection of SARS-CoV-2, Loew added.
In oncology, for now, Glympse Bio is focusing on lung cancer, but the company anticipates developing additional cancer-specific panels. Overall, for cancers, the platform is being developed to measure tumor response to therapy in real-time and tracking responses over time for immunotherapy, chemotherapy, and other therapies, Loew said.
For the detection of SARS-CoV-2 and other infectious diseases, the firm is not revealing any of its plans. However, infectious disease pathogens have strong protease-mediated responses, "so there is strong potential for us to apply our technology" in those applications, Loew added.