By Steven Levin
The MedTech Strategist
For more than 100 years, measuring hypertension has been an essential component of basic medical treatment. Yet, despite known inadequacies, the way in which blood pressure is measured has remained largely unchanged. Nueon is looking to update this process using a novel point-of-care blood test that could change the patient care paradigm.
Treating hypertension, particularly in patients resistant to drug therapy, has been a hot topic in the medical device industry over the past few years, driven largely by the development of myriad renal denervation (RDN) technologies to address this patient population. While there seems to be no end to the variety of RDN approaches (and their successes and disappointments), one basic element remains constant: the method of measuring each patient’s blood pressure. This, of course, is true not just for RDN, but for every medical treatment, starting with the basic patient exam.
A fundamental component of medical diagnostics, measuring blood pressure has remained largely unchanged since the mercury sphygmomanometer was invented in 1896. Probably the biggest change has been the recent shift away from mercury-based devices because of environmental concerns about mercury contamination. No other diagnostic procedure and certainly none as ubiquitous and important as measuring blood pressure has managed to survive largely unchanged for so long.
And, while some may suggest that sphygmomanometers are the classic example of “If it ain’t broke, don’t fix it,” the fact is, clinicians have long acknowledged that these devices are subject to a high degree of variability resulting from a number of factors, all of which affect blood pressure readings, including cuff size, the effects of patient body and arm position, and the training of those who administer the exam. San Francisco-based Nueon Inc. is looking to improve the accuracy of hypertension readings with a new point-of-care (POC) test that employs what company founder and CEO, Bob Messerschmidt, calls “an integrated approach” to blood pressure measurement that is similar to the way another chronic disease is monitored: how hemoglobin A1c is measured for diabetes patients.
Using Diabetes as a Guide
Messerschmidt has spent 35 years focusing on building biomedical instrumentation centered mainly on optics and spectroscopy. “I’ve always been interested in the problem of how do you get light, as measured by a spectral signal, into and out of samples that are difficult to assess,” he says. When Messerschmidt compares his efforts to improve blood pressure measurement with the current methods for tracking A1c in diabetes, it is based on experience. He spent most of the 1990s in New Mexico, where he co-founded Rio Grande Medical Technologies, a start-up based on technology that came out of Sandia National Laboratories, funded in part by Johnson & Johnson. Rio Grande Medical was pursuing noninvasive glucose measurement and ultimately was one of the many companies to fall victim to that challenging mission.
Messerschmidt then switched gears, and in 2008 launched Rare Light, an optical start-up that was acquired by Apple in 2010. After spending three years integrating his company into the tech giant, he was eager to rejoin the start-up world and left Apple to look for a new opportunity. Messerschmidt had nothing specific in mind. “All I knew was that I wanted to work on a big opportunity in a worthwhile area; those were my only two criteria,” he notes.
Among the different clinical spaces he explored was hypertension. “I realized that, while this is a chronic disease, physicians really have very little information to go on in managing this condition because their only real tool is the blood pressure cuff,” Messerschmidt explains. In digging deeper into this space, he found that not only are sphygmomanometers subject to a variety of factors that can yield inaccurate readings, but they might not even be measuring the most useful aspect of blood pressure because they capture peripheral, rather than central, pressure. “I started to wonder whether there was a signal in the blood that could be a marker of the risk-related effects of high blood pressure,” he recalls.
Messerschmidt found that a red blood cell’s membrane actually remodels when blood pressure is elevated. This produces increased turbulence in the vasculature. As he explains the process, “The blood cells actually recognize that they are having a hard time and send out a chemical signal that changes the molecular makeup of the membrane itself.” While that process had been identified in the medical literature, no one had thought of using it as the basis for a diagnostic tool – that was Messerschmidt’s “Ah, ha” moment. The result: Nueon was founded in 2013.
One of the added benefits of using this approach is that red blood cells are plentiful, comprising about 25% of all the cells in the body, and more importantly, are among the shortest-lived cells, generally only lasting around three months. The short lives of these cells is particularly useful from a diagnostic perspective because they can serve as an integrated tracking signal of a patient’s blood pressure over a three-month period, in much the same way that hemoglobin A1c is used to track glucose levels in diabetics. A single point-in-time blood reading that takes less than a minute could provide information on blood pressure over that entire three-month window, much like a single fingerstck to measure A1c can determine a person’s average blood glucose levels over the past three months (see Figure 1). “We recognized that would be a value proposition for physicians,” Messerschmidt notes.
Also, these cells’ plasma membranes are highly accessible to reagentless, guided wave optical interrogation. This enabled Messerschmidt to develop Nueon’s reader device technology, a highly specific analytical method to measure hypertension by focusing on the red blood cell membrane. The Nueon device interrogates the plasma membrane and spectrin mesh network using a guided wave optical measurement, and then employs a biostatistical model to correlate these optical changes to the severity and history of hypertension over the three-to-four month lifetime of the red blood cell.
Nueon’s early research has demonstrated that red blood cells’ hypertension-induced membrane changes are both unique and generate strong spectral signatures that can be clearly identified. But Messerschmidt notes that other factors can also cause different changes in the cell membrane, so the company needs to properly design its clinical trials, which are just beginning, to make sure those other conditions are represented in the studies.
Creative Financing
Bob Messerschmidt bootstrapped Nueon’s early funding to secure the company’s intellectual property and acquire the instrumentation necessary to prove the concepts. When it came time to raise Nueon’s Series A round earlier this year, he
knew that the climate for early-stage medtech investing was poor, with most venture capitalists preferring to look for laterstage deals. One of the VCs he met with referred him to Deal Labs, a new San Francisco firm that was combining advanced marketing technologies with a different approach to crowdfunding – what some call equity crowdfunding. Deal Labs looks to connect high net worth individual investors who may have experience in a particular field with investments in that field, e.g., contacting physicians to invest in medtech companies. (See “Deal Labs: Bringing a New Kind of Crowdfunding to Medtech,” The MedTech Strategist, September 22, 2014.)
It turned out that Nueon and Deal Labs both were represented by the same law firm, Wilson Sonsini Goodrich & Rosati. Messerschmidt used that connection to begin his due diligence on Deal Labs, which was just about to close its first deal – a Series A round for another medtech diagnostic start-up, Consano Medical Inc., which is developing a catheter-based device for diagnosing sepsis. (See “Consano Medical: ‘Intelligent’ Urinary Catheter Aimed at Early Sepsis Detection,” The MedTech Strategist, November 13, 2014.) Consano’s financing ended up being oversubscribed; the company was looking to raise $3 million and wound up closing a $3.9 million round, an amount similar to what Nueon was looking for.
According to Bob Messerschmidt, the company’s decision to have Deal Labs handle its Series A round resulted not only from the firm providing a good alternative to the diminishing early-stage venture market, but also because Deal Labs could speed up the financing process, which is particularly helpful for start-ups. “Compressing time is what it’s all about,” he explains. “For example, grants can be helpful, but I’ve always found the timing of the grant process to be fundamentally incompatible with entrepreneurship. And while grant money is nice because it’s nondilutive, if you spend time that you wouldn’t normally be spending, that’s actually the worst kind of dilution.” Nueon recently completed the first closing of its Series A round, having raised about $325,000, which will get the company through its next clinical trial, and is in the process of targeting a second closing to coincide with the release of those clinical results.
Messerschmidt is pleased with how Deal Labs has managed the company’s financing and would work with the firm again for subsequent rounds. One possible concern he acknowledges is whether working with Deal Labs will position Nueon for its Series B round in the same way as a traditional venture investor. “One of the things that a top tier VC will claim is that they provide a lot of help to companies in bridging to the next round, so that will be part of the grand experiment with Deal Labs,” he says. Messerschmidt’s goal is for Nueon to raise enough money in its Series A round to carry the company for two years, which will bring it to FDA approval. “When we’ve reached that point, we’ll be raising a different type of capital because we’ll be in a different situation,” he suggests.
Messerschmidt also wasn’t troubled by having to potentially deal with a large, unwieldy investor group, a common c concern with crowdfunding. In his view, “The high net worth individuals that Deal Labs is reaching out to generally have sector experience, probably a background in medicine, maybe even specifically cardiovascular, but they’re not professional investors so they’re not really looking to drive the boat. They’re looking to be a catalyst to get great ideas of the ground.”
Good Timing in a Major Market
Working in hypertension clearly met Messerschmidt’s original goal of working in a large, important market. The extent and impact of hypertension is well-known and increasing. This chronic condition now affects nearly one billion people worldwide, including 67 million American adults (31%) – three times as many people as have diabetes – and it costs the US healthcare system around $47.5 billion annually. As more is learned about hypertension, the condition has been identified as an underlying cause of a number of life-threatening illnesses, including hypertensive and ischemic heart disease, stroke, peripheral arterial disease, aneurysms, and kidney disease. Hypertension also plays a direct role in heart failure, preceding this condition in 90% of all cases. Despite its high prevalence, the limitations of current diagnostic methods mean the condition remains underdiagnosed, and of those being treated, only about half have their condition under control.
Nueon is primarily targeting those patients currently not being treated for high blood pressure, a process that should both improve patient care and save overall healthcare system costs by helping patients control their disease. The company is initially looking to target the point-of-care market with its reader device, relying on a typical razor/razorblade model that uses a single piece of hardware and disposable test cartridges. The reader has the footprint of a laptop computer, but is slightly taller, and could be purchased or leased from Nueon. A blood sample is taken from the patient via a fingerstck, deposited onto a cartridge, and placed into the reader, which delivers the results within one minute.
In Bob Messerschmidt’s view, one of the main advantages of Nueon’s device is that it will help provide actionable data to the physician at the point-of-care. Nueon’s strategy is not to have its system replace the sphygmomanometer. Rather, the goal is to provide physicians with additional, more accurate blood pressure information in a real-time setting. That in turn could potentially improve outcomes and reduce costs through more accurate diagnoses that may reduce unnecessary hospitalizations.
Thomas Quertermous, MD, chief of cardiovascular medicine at the Stanford School of Medicine and a Framingham Heart Study investigator, is Nueon’s chief medical advisor. Quertermous points out that “Clinicians underestimate the variability in blood pressure, and it’s very hard to know if the patient is being compliant.” By integrating blood pressure over a sustained period of time, Nueon’s technology “would give the physician a much better idea of what the risk-related blood pressure is for that individual,” he says. Quertermous adds, “As we gain better understanding of who is at higher risk of developing heart disease through genetic testing, it becomes increasingly important to know who we should treat and how aggressively we should treat them.”
A single point-in-time blood reading that takes less than a minute could provide information on blood pressure over that entire three-month window, much like a single fingerstck to measure A1c can determine a person’s average blood glucose levels over the past three months.
Nueon’s timing may also be propitious because, according to Bob Messerschmidt, the Affordable Care Act pushes more diagnostic decisions to the general practitioner, instead of specialists like cardiologists. “The GP needs more information to really manage hypertension properly and our device will help provide what today is a missing piece in making these assessments,” Messerschmidt suggests.
Nueon’s device is designed to enable the physician to discuss the test results immediately, at what Messerschmidt calls “that actionable moment of engagement where the physician is sitting directly across from the patient.” The reader generates a specific number assessing the patient’s risk-related hypertension, which may or may not be exactly the same number as the patient’s current blood pressure. Messerschmidt points out that some patients come into their doctor’s office with normal blood pressure, but over the course of the previous three months, their blood pressure may have spiked dramatically. Currently, physicians cannot identify those patients, but they will register on Nueon’s system.
“Those people really should be on some sort of treatment and our value proposition is that this will enable doctors to identify this undertreated population,” he explains. The company’s device will also identify situations where patients are not taking their medication or are taking it improperly, helping to improve compliance. According to Messerschmidt, “It’s a way of giving the physician more and better information to manage the disease because all of the long-term health complications of hypertension are really related to the integrated pressure history.”
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