Ann Arbor, Mich.-based startup Endra Life Sciences Inc. started out focused on a photoacoustic imaging tool for mice in the lab, but in recent years it has shifted gears. Now, it aims to secure the go-ahead next year from European and U.S. regulators to launch a thermo-acoustic enhanced ultrasound system designed to quantitatively assess liver fat, known as TAEUS.

Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in the liver. It’s associated with obesity and type 2 diabetes. Roughly one-third of these patients have a more severe, symptomatic form, known as nonalcoholic steatohepatitis (NASH), in which inflammation and liver damage start to set in.

Zeroing in on NAFLD

But there is little preventative effort when it comes to NAFLD/NASH. It’s often not diagnosed until it reaches the more severe stages of disease, since the tools required are magnetic resonance imaging (MRI) or a liver biopsy. Both of those options are costly and inconvenient, with the latter carrying some risk to the patient.

“We're able to quantify fat in the liver and that's what is at the base of the NAFLD condition – and also the root cause of the inflammation and NASH,” explained Endra chairman and CEO Francois Michelon to BioWorld MedTech. “We take a very quick, noninvasive, virtual core sample. Just like a regular ultrasound workflow, we have a probe to place on the side of the patient. It takes a two-second scan and we quantify fat in a way that a traditional ultrasound cannot.”

“Typically, a physician sees someone come in either for a wellness check or an annual physical and they'll do a blood test for liver enzymes,” he continued. “It’s a common panel and there may be liver enzymes that show that something is amiss in the liver, but those enzymes can’t tell me how much fat there is.”

A simple ultrasound might be the next step to determine if the liver is enlarged – and then, particularly if the patient is symptomatic, that might be followed up by MR imaging or a liver biopsy. There are currently no FDA-approved treatments for NALFD/NASH beyond weight loss, but there are several drug and device candidates that are in the pipeline.

The idea with TAEUS is to provide a relatively inexpensive tool to identify NAFLD early, before it has started to damage the liver and may be more easily reversible to avoid eventual fibrosis or cirrhosis of the liver. With the rampant obesity epidemic, it is believed that more than 1 billion people globally may have NAFLD.

Endra is aiming for use of TAEUS by physicians with patients, but it expects the technology could be useful for the many ongoing trials in NAFLD/NASH. Fatty liver is difficult to quantify and define routinely and consistently, and the company has had some interest from biopharma companies looking to better do so in their clinical trials.

It plans to submit TAEUS to FDA and European regulators during the first half of 2020, with a launch expected to follow around mid-year.

Clinical trial tests

Endra has already conducted a first-in-human feasibility study of Taeus in 50 subjects. It compared the devices’ ability to quantify liver fat in humans with magnetic resonance imaging proton density fat fraction (MRI-PDFF), which is the gold-standard measurement.

In that study, it aimed to discern patients above and below a threshold of 6% fat, which is typically considered clinically relevant. It had a sensitivity of 88% and a specificity of 82%; sensitivity being the ability to correctly identify patients with disease, specificity being the ability to correctly detect those without disease.

The company has since been focused on improving the accuracy and the form factor of the device. Now it’s slated to start another study using those newly updated, pre-production systems in a 75-patient clinical trial. It aims to ultimately expand that study to multiple sites and several hundred patients. TAEUS is expected to follow a 510(k) clearance pathway with the U.S. FDA.

Thermo-acoustic enhanced ultrasound is designed to offer an accessory and software to existing ultrasound machines. It can visualize human tissue composition, function and temperature in ways that are currently only possible with CT or MRI. The point-of care device is also much less expensive at around $50,000 vs. the more than $2 million for an MRI machine that also requires a dedicated hospital room.

Once TAEUS is launched, Endra also plans to further explore another additional application of its technology: monitoring tissue temperatures in real-time during electrophysiology procedures such as ablation. These currently can’t be easily monitored, but the thermo-acoustic enhanced ultrasound can detect the temperature of target tissues, whether the ablation source is hot as in laser ablation or cold with cryoablation, to ensure that the tissue is properly treated.

After the IPO

Ahead of regulatory clearance, Endra has been hitting the medical conference circuit to generate physician interest with one of its latest stops at the recent American Association for the Study of Liver Diseases (AASLD) meeting. It aims to appeal first to radiologists, as well as gastroenterologists, hepatologists, endocrinologists, as well as internal medicine specialists and even primary care doctors. Awareness of NAFLD/NASH is increasing in lock-step with its increased prevalence, as well as the emerging potential to treat it.

Endra has a partnership with GE that dates to 2016, but that is slated to end in January. The company sees its technology as a good fit for a partnership, since ultrasound innovation has traditionally been introduced to the market via the large imaging players.

Endra will likely need to do some fundraising to support its ambitious plans; it had only $2.3 million in cash as of Sept. 30 and a third quarter loss of $3.4 million. That could prove challenging, since it is the rare, pre-revenue public med tech. It conducted an IPO in June 2017 to raise $8.4 million at a valuation of $16.8 million, but since the IPO, its shares have trailed downward to a price of about $1 vs. $5 at IPO. That gives it a current market cap of only about $7.5 million.

“It was perhaps a little unorthodox that we went public as such an early stage company, but I think we were fortunate to meet the criteria and get the investment interest to do a straight IPO on the Nasdaq,” said Michelon. “It is on the challenging side for a small company. Being publicly traded on the Nasdaq is a pretty heavy burden in terms of legal and auditing costs and all the work and time and bandwidth that we have to devote to meeting the rigors of being listed on the Nasdaq.”

“Our long-term holders have benefited us, so I would say, without speaking to you know any plans to raise capital, when we want to raise capital – it's a fairly liquid currency for us to be listed that way,” he added. “So, as we get bigger, as we come into revenue next year, I think it'll be particularly attractive and less burdensome relative to where we are now.”

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