BALTIMORE – Australian health technology startup Nutromics is using DNA-based biosensor technology licensed from the University of California, Santa Barbara to develop a noninvasive, continuous molecular monitoring medical device that it initially hopes to enable applications such as antibiotic monitoring.
Much further down the road, the company foresees applications such as detecting acute kidney injury, sepsis, and cardiovascular diseases, and eventually preventive medicine.
The Brunswick, Victoria-based company, now with nearly 30 employees, obtained the exclusive rights to electrochemical aptamer-based sensor technology developed by Kevin Plaxco's lab at UCSB around two years ago.
Nutromics thus far has generated very little clinical data to support the journey of its technology out of the research lab to the real-world clinical setting, but the company clearly has its sights set on such use: Last week, it appointed former Abbott Laboratories senior medical director Agim Beshiri as its inaugural chief medical officer.
According to Nutromics Cofounder and co-CEO Peter Vranes, continuous molecular monitoring has been the "heart and soul" of the company since it was founded four years ago. Along with Cofounder and co-CEO Hitesh Mehta, Vranes started Nutromics to commercialize noninvasive, real-time ways to surveil molecular targets inspired by continuous glucose monitoring.
The company's current capital consists of a mixed bag of government grants and investor funding from pre-seed and seed financing rounds, according to a company spokesperson. So far, the firm has raised A$10 million (about US$7.4 million), with backing from CP Ventures and Artesian Investments.
Since its inception, Nutromics had trialed various biomonitoring ventures, including characterizing skin carotenoids for micronutrient deficiencies and tracking glucose levels noninvasively via optical or sweat-based methods, Vranes said. But none led to commercial success. Then the cofounders came across the aptamer-based technology at UCSB, which Vranes considers a game changer for the company.
Touting the approach as "the holy grail for biosensing," Vranes said that aptamer technology, which is in essence DNA-based biomimicry, deploys engineered synthetic DNA strands, or aptamers, that can bind to targeted metabolites and subsequently change shapes, emulating the sensor molecules within our body. By anchoring one end of the aptamer on an electrode surface while attaching a methylene blue dye to another, researchers can measure the conformational change of the aptamers via induced electrochemical signals, gleaning real-time concentration information of the target molecule.
In addition, aptamers are designed to mimic the reversible nature of a biological sensor protein, meaning they can bind to or unbind their target substrates by working in an equilibrium, Vranes said. As a result, aptamers are able to continuously monitor the target analytes in a theoretically perpetual cycle.
Since Plaxco designed the electrochemical aptamer-sensing technology, his group has developed 12 different aptamer-based sensors for targets including vancomycin, doxorubicin, and cocaine, and demonstrated the aptamer technology's utility in live rats. The UCSB team has also applied a series of multi-jurisdiction patents for the technology, Vranes said.
The high specificity of each engineered aptamer also affords them the possibility to concurrently detect various targets in the same sample — just as our body can detect different analytes at once without interfering with each other, said Beshiri. "In in vitro diagnostics, where I played [a role] for many years, we are not able to detect multiple analytes in the same sample at the same time," he added. Beshiri said the aptamer technology's potential was one of the motivations for him to jump ship from Abbott to Nutromics.
At Nutromics, Beshiri will lead the company's undertaking to harness the aptamer sensing technology into a real-time vancomycin monitoring device for critical care patients, the company's first target application.
A somewhat thorny antibiotic, vancomycin — often administered to critically ill patients — has a "very narrow" therapeutic range, above which it is toxic and below which ineffective, Beshiri said. According to him, conventionally, clinicians gauge initial vancomycin dosing for a patient based on the individual's age, body mass index, and other factors. Then hours after the infusion, the care team will attempt to measure the peak blood vancomycin concentration as well as the ensuing vancomycin clearance to help adjust the next optimal dosing for the patient.
"If you're measuring a peak, you've already infused that full bag of vancomycin," Beshiri said. "But the damage is already done." That said, the real-time feedback capability promised by aptamer-sensing makes the technology suited for vancomycin monitoring, which will allow clinicians to make dynamic dosing and titration adjustments to ensure patients' safety, he said.
Therefore, instead of directly targeting consumers as some household continuous glucose monitoring systems do, Nutromics' vancomycin monitor will primarily be designed as a piece of medical equipment for the critical care setting — just like an electrocardiogram machine or oximeter, Beshiri noted. To that end, the company also considers the US as its first market and is currently setting up a US office, Vranes said.
Mechanistically, Vranes said, Nutromics' device is designed to target the interstitial fluid, the intercellular fluid just under the skin. "We're all bathed in this fluid," he said, pointing out the fact that humans have roughly three times as much interstitial fluid as blood. According to Vranes, the device will comprise a microneedle that contains aptamers at the end of the capillary, and a wearable coin-sized smart patch capable of wirelessly transmitting real-time data to software.
Although different types of aptamers can in theory work in parallel without interference, Beshiri said they still have to be physically separated by different microneedles to prevent one aptamer's electro-conductance signal from being masked by another. The company so far managed to fit two needles on the same patch, though Beshiri emphasized that it is the physical real estate of the patch that is the limiting factor, not the sensors.
"You don't technically want to patch the size of a frisbee on somebody," he explained, maintaining that even physical separation in the same sample is "still unheard of" in diagnostics.
Even though aptamers can recycle themselves through equilibrium presumably in perpetuity, Vranes said Nutromics' first vancomycin sensors are anticipated to last around 24 hours to correspond with the clinical workflows. But he said the company has internal data to show that the sensor can potentially last for days and even longer. Vranes also acknowledged that the longer lifespan of the sensor can render the technology to more applications, such as remote patient monitoring.
As for detection speed, Vranes said aptamers are designed to achieve a millisecond resolution. However, he said that data frequency might not be necessary for many applications, especially for non-acute molecular monitoring.
Although the Plaxco group has primarily published data on the aptamer-sensing technology in a live rat model, Beshiri said Nutromics has demonstrated its viability in vitro with human serum samples that have been spiked with vancomycin.
Beshiri said that Nutromics is currently rolling out a Phase 0 interventional study in collaboration with Monash University's medical center to interrogate the biosensor's safety and feasibility in as many as 10 humans by injecting healthy participants with vancomycin while investigating the technology's monitoring performance.
In addition to the safety study, the company also plans to conduct "abnormal studies," where the aptamer sensor will be tested on pathological ICU patients toward the end of the year, he added.
But that will still likely be the tip of the iceberg for securing the platform's clinical approval, which Beshiri called "a 2025 type of target" for the company. "We have quite a ways to go," he said, adding that the company still has to validate the technology in many more clinical studies involving hundreds and maybe thousands of subjects before it is ready for clinical use. "That is not a trivial thing," he added. "It has to be good enough for my kids before it can be used on yours."
Although Nutromics is currently focusing on biosensing for chemical analytes, Vranes said the technology can also potentially be synergized to monitor biomarkers associated with kidney injury, sepsis, and heart failure in the long run. Ultimately, he said the company hopes to step in the preventative medicine market.
"We want to be all in on prevention," Vranes said. "That's a much longer-term vision. But that's where we would love to get to."