A 23-year career in the Israeli Navy might not seem like the ideal background for a medical device company chief, but for Integrity Applications chairman & CEO Avner Gal it turned out to be the perfect pedigree.
Gal told MassDevice.com that his time as a developing engineer in the Navy gave him the opportunity to spearhead the creation of an electronic warfare suite that’s still in use on Israeli ships and submarines, an experience that has helped him in launching other projects.
"I came up with the idea, I chased after the budget, I did all the marketing, and everything exactly like a startup," Gal told us. "That was my 1st baby; this is my 2nd baby."
The "2nd baby" is a non-invasive blood glucose monitor developed by Integrity Applications. As CEO for another startup, Gal said, he met up with co-founders David Freger and David Malka. Freger, a diabetic who hated pricking his finger to test his blood glucose, was the 1st to suggest that there was an alternative to the optical methods for non-invasive testing that other companies were pursuing.
"The 3 of us became very good friends and liked to work together. When David [Freger] came up with the idea, I said, ‘Okay, let’s do it.’ That’s how it all began," Gal said.
The Integrity Applications device, the GlucoTrack Model DF-F, uses ultrasonic, electromagnetic and thermal technology to measure physiological changes associated with blood glucose levels. The device uses a small ear clip to take its measurements, then applies a proprietary algorithm to deduce blood glucose levels.
Following is a transcript, edited for clarity, of our chat with Gal:
MassDevice.com: Your flagship product is the GlucoTrack DF-F, named in honor of your co-founder, the late David Freger. Tell us about the device and how Freger inspired the Integrity Applications mission.
Avner Gal: He was diabetic, and like many other diabetics, he wouldn’t prick himself, no matter what. Just wouldn’t prick himself. We used to work together in another company in the industry, nothing to do with medical. At 1 point he told me, "Let’s develop a non-invasive glucose monitor that will please my life, as many others." I said, "It sounds interesting, it sounds challenging, let’s do that."
I’m blessing this other company every single day. They for some reason didn’t want to do it over there, thank God, so we decided to resign with another guy, David Malka, who was the COO of that company. We started to think about it, spending many hours in restaurants and coffee shops, and came up with the idea. With our own money we started to do that in a garage. We did the feasibility study to know that we have something in mind, that the idea that we have in mind, it makes sense.
That’s actually how it all began. Unfortunately [Freger] passed away at the age of 48 on Dec. 30, 2004, because of complications of diabetes. It was an early stage of the company, so at that time I was very, very concerned about being able to do it, because he was the CTO. We had enough manpower that had the knowledge and everything in engineering, but after all he was the CTO, so we were concerned about it.
So we sat down together for a few days, making sure that we were able to finish the product. Not to continue. Continue is a nice story, but to finish, that’s that idea. After the team convinced me, after very, very tough questions, that indeed we are able to do that, I said, "Let’s go for it." Then we decided to memorialize his name by calling the device after his name.
MassDevice.com: Tell me about the Freger device – what’s the “special sauce” that separates it from other non-invasive glucose monitors?
Avner Gal: Now we could spend about 2 weeks on that. It’s a very unique approach. That’s what we are very proud about and that’s actually why we are with already a device, because of the very unique approach. When we did the feasibility study at the very beginning stage of the company, or the garage shall I say, we came to 2 conclusions.
One, optical technology, which was the leading technology at that time (and many others still try to use it), we concluded that it cannot work and it won’t work. Eventually, after a few years, some others came to the same conclusion, after spending over a billion dollars in the field. That was 1 of our very, very 1st conclusions and that’s why we didn’t touch it. From Day 1, we didn’t touch [optical] technology.
The other conclusion was that we didn’t come from the medical arena. It sounds like I’m shooting myself in the foot, however eventually that was found to be our advantage, because we were completely unbiased. We came from the measurement devices arena, so we thought, "Okay, we have to measure glucose, fine." The material that you have to use is the human body. That’s a very complex machine. We are not actually dealing with really reading the glucose, but we are doing an indirect measurement, because we are actually reading some physiological phenomena in the body which are correlated with the glucose. We have noise in the measurement process, and what do you want to do? What every engineer always dreams about, increasing the signal-to-noise ratio. That’s the mission.
We have to treat the noise, just the noise. Our idea of reducing the noise is to come up with a variety of technologies to work simultaneously, and to combine them together, and maybe we can reduce the noise. That was our initial idea. Eventually we came up with the magic number of 3. On one hand it gives you enough data to indeed reduce the noise; on the other hand it’s still practical to combine them together in the same device. That’s how we came up, eventually, with the number 3.
Then we had to find out the right technologies that could work together, and I tell you that was a hard mission because they were interfering with each other and we wanted to do it simultaneously. Eventually we came to the conclusion that that’s a mistake, let’s do it sequentially. Still, the whole process takes about a minute, so from the user’s point of view you can still call it simultaneous.
We have ultrasonic, electromagnetic, and thermal. Each 1 of the 3 is active technology. That’s very important to understand. When the body gets into hypoglycemia the temperature rises and the body starts to sweat. One of the ideas is to measure the temperature, or the relative temperature, or the increase of the temperature, and the sweatiness level. By then you can alert for the hypoglycemia.
That is not our case. That is passive. What we are doing, we are using all active technology. Meaning, if we talk about the thermal technology, we are heating the tissue. No worries, we don’t do any barbecue, the users don’t feel it. We heat and then we are measuring the delta temperature, the increase of the temperature, because of this heating. Actually, in a way, we are measuring the heat capacity of the tissue.
The same idea goes for the other technologies. In the electromagnetic for example, we are inducing some signals at a very, very low intensity in order not to cause any problem. We are measuring the conductivity of the tissue, which is caused because of this induction.
The ultrasonic is very easy to explain. If you beam an ultrasonic signal through some kind of material, based on the characteristics of the material, the speed of sound through that material will change. We are beaming some ultrasonic signal with a given known speed through the tissue and we check the tissue impact on the speed of sound. By again doing the calibration, sort of reducing all the impact of the constant components, therefore we are able to know what’s the impact of the blood itself.
At the end of it we have actually 3 different signals, and then we combine a very sophisticated algorithm that we developed as well. It gives a different weight to each 1 of the signals and calculates it with leverage. That’s really great.
MassDevice.com: The device has CE Mark approval in the European Union. What markets are you in overseas now?
Avner Gal: At the moment I can refer to those markets that we already have signed agreements, distribution agreements, because we are doing our sales only through distributors.
We have Turkey, Australia and New Zealand, and we have Lithuania, Latvia and Belarus. Those are already signed. Without disclosing, because I cannot at the moment, there are some others under negotiation. Very promising. It’s a matter of days to weeks that we’ll disclose the others. [Editor’s note: Since our chat with Gal, Integrity Applications has signed distribution deals covering the Philippines and Chile and Italy, Thailand and Uruguay. The company also landed an expansion of its CE Mark to cover a 6-month calibration window for the device.]
For the U.S. market we have to have FDA approval, of course.
MassDevice.com: Are you on the 510(k) clearance track or the pre-market approval track with the FDA?
Avner Gal: It’s PMA. There’s no predicate device. We spoke with the FDA in the past for pre-IDE meetings, so we sort of understand through to that very moment. We are going to start or to re-accelerate the process with the FDA pretty soon. We prepared already the pickup article, we have to submit them, get the approval. We are going to do the trials in UCLA with Dr. [Andrew] Drexler, and that’s already agreed upon with him. We have had a relationship with him for quite a few years. We don’t have to chase after a place to do it, and UCLA is considered a very prestigious place for diabetes.
MassDevice.com: How much has Integrity Applications raised so far? Is it enough to cover the U.S. clinical work?
Avner Gal: First of all, you have to understand that it’s very simple, this trial, very simple and very "unrisky." That’s why the issue is very, very basic. Overall we’re talking about relatively very cheap trial. You need a very accurate machine [for the control arm]. We’re using the most accurate device, the gold standard. It’s not a home use, it’s a clinic use.
We decided in the very, very early stages not to deal with VCs. I tell you retrospectively that I’m extremely happy with this decision. It’s made my life much harder, but still I’m very happy with this decision. The original money, let’s say within the early 6 years or something like that, was from friends and family as well. Actually not friends and family, because we didn’t want to risk the family and the friends, but angels.
Then we engaged with [investment bank] Andrew Garrett, 1 of the early investors used to work for them at that time, and introduced us to Andrew Garrett. We raised a total of $15 million on top of the $12 million angel round.
MassDevice.com: Integrity Applications is planning a portfolio of devices built around this technology. Can you tell me about that?
Avner Gal: Yes. The most important is to understand that all of them are based on the same technology, or will be based on the same technology. Just so my lawyer will not kill me, I say I cannot guarantee that we’ll develop all of these devices. Now we can talk.
Actually the first 1 in the list, the DF-B, it’s a basic 1. It’s a downgrade of [the DF-F]. It’s only basic. Just make a measurement and that’s it. That’s for developing countries and emerging markets. That’s already been started, because it’s the easiest.
The others are continuous monitors for night alerting, for the hypoglycemia episodes, for drivers, incubators, a variety of others. Again, those are in our mind at the moment. The ear clip for the continuous monitors would be different, it would be wireless of course. The shape will be like the Bluetooth devices. Nobody will walk in the street with something like that. We don’t expect them to do that. For an example for the DF-B, that’s exactly the same ear clip.
In the meantime we’re already developing an earpiece which is by far smaller. Not the device itself, not the ear clip itself, but the sensor. Because the earlobe must be big enough to take this. For small kids, we are talking about the age of 6 and above, so for small kids it’s too big. Some people with relatively small earlobes, that won’t fit. We developed actually an ear clip, again, a sensor, that is about the size of this tip, so by far smaller. It’s already been developed; it’s now in clinical trials.