Empower Your Diabetes Management With Tech

Rich Yang

Thanks, Will. I’m happy to be here. Thoughtful introduction in thoughtful, kind words. appreciate it.

William Hsu, MD

When I take a look at the landscape of diabetes today, I want to ask somebody about what’s not and what’s good in the diabetes space from a technology standpoint, I cannot think of a better person than to come to you, Rich Yang. Tell us a little bit about your history, your journey, and what you are doing these days.

Rich Yang

I’ll just keep it very simple and very quick. I’ve been at MedTech for 25 years. I learned a lot about the diabetes space from you as my mentor for many years when you were at Joslin Diabetes. So the first part of my career was in product marketing. One of the early product managers for the CGM category, I was at Medtronic for almost eight years and learned the ropes on the ins and outs of medical devices, including MedTech insulin pump therapy, among the great products that Medtronic continues to get out on the market. I had a great chance to spend nearly a decade at Dexcom, and again, a great technology we had a chance to take from the early years when I joined and spent about a decade and left in 2017. I had a chance to join from there and open my career or expand my horizons a little bit and get some exposure over at Foxconn for a couple of years.

William Hsu, MD

That’s the manufacturer of the iPhone.

Rich Yang

There is a bigger view of tech, health, tech, and consumer tech combined. We spun out a venture fund from that experience. Biolinq is the only non-revenue-generating investment, so I invested in two rounds of Biolinq in the early years. Three years ago, Jared Tangney one of our co-founders and our current president and chief technology officer. He asked me to come in and join him on this journey as CEO, and I couldn’t be more humbled to be here working on this platform with intradermal continuous sensing.

William Hsu, MD

That was it. such an impressive background here that you brought in a lot of words we want to clarify, then CGM stands for Continuous Glucose Monitoring. Now, a CGM used to be such a new idea, but now it’s such a hustle technology as well. Rich, you may be wondering, a lot of the listeners to this show wanted to reverse their diabetes, but in the process, they still needed to know where their blood glucose was. They want to know what the trend of their glucose improvement is. Is it getting better? It is not getting better. So data becomes such an important tool for decision-makers. also a feedback loop to your behavior change. Tell us broadly, Rich, about this glucose monitoring field. You’ve been in this for 25 years now. Certainly, we’ve witnessed some of the biggest dramatic changes over the years. So take us through a little bit of that journey. What was it like, and where are we now?

Rich Yang

If we go back to 1999 for the very first CGM, it was wired. You were tethered to a piece of hardware with the sensor connected to it, and it was blinded mode diagnostic only. So we had a chance to travel the world and teach endocrinologists and collaborate with endocrinologists about how we can use this information to drive better outcomes in modifying therapeutics and regimens and the world-class insulins and medications that have been available. So it was an extraordinary experience to then go to Dexcom and see the amazing work done by the JRF in driving the outcomes needed to get continuous glucose monitoring reimbursed. It’s a very expensive proposition to run large outcome studies with this technology, Because of all of that work, companies like Dexcom, Medtronic, and Abbott now have reimbursed platforms for glucose sensing and continuous glucose monitoring. But a real leapfrog came when the technologies became mature enough to get to the factory type of no-calibration platform. 

William Hsu, MD

What does that mean? Help our listeners understand the factory calibration. What does it take? Why is it important?

Rich Yang

Fingersticks have been the gold standard for a very long time, decades, and so fingersticks with glucose meters were still required to make sure that the continuous glucose monitoring systems were still reliable and accurate. In the early years of CGM, fingersticks were needed to calibrate, and it was several fingersticks a day. Then it got cut down to one or two finger sticks a week. Now you have sensors that last 10 to 14 days and no calibration at all. Anything we could do to remove the need for fingersticks is a huge barrier for those who are not so comfortable doing it so frequently. With the ease of use of technology today and the accuracy of its performance, it’s quite astonishing to see how far this has come over the last 20 years.

William Hsu, MD

Certainly has brought benefits to many people living with diabetes now. But I remember when I was in practice, prescribing continuous glucose monitoring of monitors for patients without insulin was such a challenge. Most of the people that are listening to our show today do not have Type 1 diabetes. They have Type 2 diabetes. The cause has been a problem although many people want to have the benefit of having a meter that continuously tracks glucose without having to reach for the stick and prick a finger. What do you think is the industry is getting richer? There have been so many other interim technologies they have; they’re promising to be very helpful, from light skin using the light spectrum to you can imagine, to even contact lenses that they’re supposed to be able to monitor, to monitor blood glucose, but they haven’t become mainstream at all. What are the challenges in measuring glucose? Let’s take a little bit deeper and dive into the technology aspect.

Rich Yang

Type 2 diabetes is not intensively managed, not on insulin. This is a frontier that is very important to companies that are working on technologies for continuous sensing. The pathway to noninvasive sensing has been challenging. We haven’t seen one get through the FDA in 20 years, where we’ve seen a lot of press releases and a lot of research and science around it, but it’s still not quite there in terms of a viable product to expand the use of continuous sensing in people who are not on insulin. The current devices that are approved today for people using insulin are also wonderful and very accurate. and one of the biggest barriers is the ease of use. Could it be less complex? Could it be easier to prescribe? Could it be easy enough to put on a bandage from home without hours of training behind it? There are multiple assets to this, from the user experience with the device itself to the perceived anxiety around trying something new. Is there a needle attached to it? What does the data mean for how people look at information about health care? If you’re not on insulin, especially around metabolic health? What does the information mean to those who are not on insulin? In other words, what does it mean if I’m very high for extended periods? What can I do about it? Two main questions that need to be addressed come from the industry in terms of innovation, which are: am I okay and what do I do? Simple as that. There could be a solution that lets you in real-time. Are you okay? Good. That’s a check-in because, especially with Type 2 diabetes, a lot of the time people don’t feel sick. Why take medications or a daily pill if I’m not feeling symptoms or sick? It’s very similar to saying I’m not going to be taking aspirin if I don’t have a headache. Adherence becomes very difficult if you don’t have relevant information for you to consume, digest, and understand. What other pathway is better than having a continuous sensor that’s giving you real-time feedback? Where the technology is going and where it should go is to address the three fundamental tenets of sustainable behavior change in cognitive restructuring. These are behavioral science principles that have been around for a very long time. It’s nothing new here for your audience. However, three things need to happen to support cognitive restructuring and real-time feedback. That’s an obvious one: passive, real-time feedback when teachable moments arise. If I can get this real-time metabolic health feedback immediately after I drink a glass of orange juice, I can see what that does. Sorry, my office light is dimming. I’ve got this motion sensor here, so if I can get that real-time passive feedback after a glass of orange juice, I can then understand my relationship to foods like orange juice. If I can understand my relationship with activities like exercise and if I can understand my relationship with the medications I’m taking, I can do that conveniently and cost-effectively with passive real-time feedback. That is the innovation that would inspire opportunities for people to reverse diabetes. ? The cause-and-effect relationship is everything.

William Hsu, MD

What you said is so timely. In our society right now, it’s the age of information overload. We’re getting so much information, but even glucose information as well. If you get a reading that spits out to you that gets captured every five minutes or so, that’s a lot of data. How do you digest that? And the challenge for a lot of our listeners living as people with Type 2 diabetes is the fact that what do you do about it? But what is the actionable information they can use? That’s truly challenging. Now we’ve outlined the questions. We will outline the problems; what are the solutions? Where is the industry going? Right now there are two dominant brands, and there are some other emerging companies, but it is still very much the same technology. You have a continuous glucose monitor. The size is getting smaller. It’s still involved in the insertion into the tissue. Are you still feeling a little bit of that invasiveness right into the skin? Then there is also the profile of the CGM that sometimes you can pop into a wall and knock it off. It’s helped a lot of people, but where are we going as an industry? You are one of the most innovative companies in this space. Tell us a little bit about Biolinq and what you guys are doing right now.

Rich Yang

Thank you. Biolinq was founded almost 12 years ago by two PhD students out of UC San Diego, Joshua Windmiller and Jared Tangney, as co-founders, they went about an orthogonal way to look at sensing, and because they didn’t have any historical context coming out of their school programs, they went after Moonshot, meaning they looked at how to take a different approach using Silicon Microneedles. This is looking at a scale opportunity, the likes of which the world has not seen before for wearables. How do you etch microneedles out of a silicon starter material and have independent standalone electrodes across an array of these microsensors that are so small that they sit right on top of the capillary bed? They have known that the most metabolically active tissue in the body is the upper strata of the particular dermis. The papillary dermis is where the microneedles reside.

William Hsu, MD

That’s part of the skin.

Rich Yang

If you can have microsensors that can be put on without any pain, they don’t go deep enough to cause any bleeding. It doesn’t hit any capillary tissue or bed. But we’re sitting on top of the capillary bed. There’s good perfusion, and there’s no lag time for glucose. Glucose information is easily accessed with electrochemical cells and sensors in this space. That was their dream.

William Hsu, MD

I need to interrupt you for a second there because our listeners are just like their eyes glued to the monitor right now. When you say microneedles, how micro are they? How severe it is when you talk about needles.

Rich Yang

Let’s use a strand of human hair as an example. Each one of the microneedles that was developed under Biolinq is about 200 times smaller than a human hair filament. 200 times smaller. There is an array of these microsensors that are on a two-millimeter by two-millimeter di, and that is what is at the base of the sensor. When on the skin, you don’t feel anything. So it doesn’t go deep enough to draw any blood. It doesn’t go deep enough to hit any nerve endings. They don’t feel any pain, which is probably the closest you can get to a noninvasive experience, but it is still powered by electrochemistry. By the way, I must have a disclaimer here. Biolinq has still not yet been approved or cleared by the FDA. This is still an investigational device. It’s come a long way over the last 12 years. I’ve been an investor here for several years. But three years ago, when I came in as an operator alongside Jared Tangney, who is now our president and CTO, the opportunity to access this compartment of the skin was a big win. It’s now the sensors that people are willing to use that will drive the large majority of the volume when looking outside of, let’s say, insulin-using people with diabetes. I would argue that the value propositions that come from having an array of sensors for the redundancy to make sure that what we’re sensing is accurate and reliable continuously have a substantial value to people on insulin as well. In addition to not having any potential scarring from having filaments on the skin, whether it be you no longer wear infusion sets for insulin delivery or longer wearing glucose sensors, These microsensors don’t go deep enough to cause any scar tissue. Insulin absorption has been very important for people with insulin. But for people who don’t take insulin, it’s a noninvasive experience. Very little training, easy to deploy; You can’t feel it.

William Hsu, MD

This is such a promising future. A lot of our listeners, although there are not many people who take insulin in this crowd, want the information, not only for medication adjustment but for lifestyle change as well. They’re looking at what they eat, how it impacts their blood glucose, and whether their activities are helping them. The idea now is invasiveness. It’s very appealing because you’re not using it to adjust your medication. your tradeoff. Your willingness to trade for a needle insertion now changes. You want something easy and that’s helpful. A lot of people have it.

Rich Yang

I’m sorry to interrupt you. I was going to say technically still considered minimally invasive. Even though the experience is not technically considered minimally invasive,

William Hsu, MD

When you think about the depth of that insertion that’s so small compared to the thickness of a hair, that’s going to be a different experience.

Rich Yang

No introducer needle is required to place it into subcutaneous fat. One of the other tiers of a microarray.

William Hsu, MD

Thank you for disclosing that this is not yet commercial. But the purpose of this conversation is to let our listeners know what’s coming. 

Rich Yang

I feel that in terms of what’s coming, we’re now in this world where there’s just mental information everywhere. There are so many wearables out there. The progress that the Apple Watch has made is extraordinary, with all of the information now on your wrist. but there are so many different devices that need to be integrated and synced on the back end. One of the promising opportunities is to combine all this information into one single wearable. Because a company like Biolinq didn’t have any legacy hardware or manufacturing to begin with, there are no limits to how we architected the technology stack. Knowing that context is important, we were able to design a wearable with continuous glucose, with redundancy built-in, but also with activity built into the chip in addition to sleep and temperature. Understanding the context around your metabolic health provides deeper insights to inspire and inform, so the economies of scale are here to do it, the off-the-shelf technologies are here to do it, and we just combined it all on a single device. that makes it easy for anyone to just have this information available without having to orchestrate a synchronization of five different devices.

William Hsu, MD

Wear five separate devices.

Rich Yang

Then there are ten different apps to combine everything and then try to translate all the information from that. It’s one of those things that have been that has opened my eyes. This is the first time in 25 years—20 of those years—and sensing where I can see context around my metabolic health. For example, one of my glucose levels is high from an unhealthy meal, and I walk around for 15 to 20 minutes. I can see the direct correlation between that walk and seeing my glucose levels drop all under one visualization without having to sync things off of my other devices. That’s been extraordinary for us to see, especially those of us who have been in the space for so long. We’re missing color. 

William Hsu, MD

For sure.

Rich Yang

Without having that additional context.

William Hsu, MD

Even in the days of episodic glucose monitoring, when you have to prick your finger, there are offerings out there that look for more than glucose. You can also check for ketones. That was helpful for people with Type 1 diabetes, where ketone and glucose levels were both helpful, and yet they used two different strips, but it’s still the same meter. Is it in store for the future for technology that looks at microneedles and other sensors? Can you speak to that?

Rich Yang

In an industry as a whole, everybody’s pursuing additional analytes. The most stable form of continuous monitoring has been glucose because of the characterization and availability of glucose oxidase. The foundational enzyme is used to sense glucose. So enzymes are very finicky. So it’s been very hard for the industry to come up with new sensors that are enzyme-based. There are so many natural enzymes or a limited number of natural enzymes to use to sense things like lactate. For example, with lactate oxidase glucose, clearly, glucose oxidase has been around for decades and decades, is very well characterized, and performs very well. But every time you try to sense a new analyte, it’s a whole new chemistry. It’s a huge undertaking to stabilize it for in-vivo sensing, to have it dry storage and shelf life, and for it to perform with or without calibrations. It’s an entirely different chemistry, so the value of other analytes is huge. Now combining multiple analytes under a single device, is an even greater orthogonal challenge that hasn’t been solved, although it is very much in the spotlight in terms of funding for academic research. But no company has yet taken advantage of the new economies of scale and the technologies that are out there to sense other markers outside of enzyme-based electrochemistry. We’re in the first real decade of human history, where we can now synthesize biology. Biology has been an observational science for human history up until this decade. So there are a lot of new, exciting opportunities to synthesize biology and to leverage these technologies and put them on sensors to tend to measure other biomarkers that traditionally have not been possible. There’s been a lot of academic research around this for many years. Now is the point in time where the platforms that can leverage these technologies and deliver them into sensing in vivo continuously are at the forefront of what’s to come in the next decade. Getting to a continuous metabolic health panel on one array of sensors, for example, would be extraordinary. For both people who don’t use insulin and for people on insulin, activity is a huge part of driving glucose levels down. Understanding when that happens accurately, combined with other measures like lactate, ketones, and glucose, all combined in one means that those opportunities are now in front of us. 

William Hsu, MD

Richard, this has been such a helpful conversation. This interview intends to instill hope in people who are listening to us right now. They’re living with diabetes, and they’re trying to get to the cutting edge of reversing Type 2 diabetes. but just to know that folks are working on new-generation technology. What we heard from Rich is that it’s not only the integration of all the technology, the platforms, and the ability to sense multiple analytes, but also the desire to integrate all these functions, from sleep to activity, to the dual position—you name it—whatever’s possible right now. There are great technologies, such as Apple and others, that platform that’s already there for integration, and back-end integration. This is truly a great time for the next generation of technology and a new paradigm of care to emerge. Lastly, I always wanted to end our conversation with a little bit of a personal note. I came out of medicine into my current company to help drive the category-defining science and products and services so that we have a new path to disease reversal. What drove you, as a person, to come in to work at a company like this and drive the forefront of technology to the next stage? Tell us a little bit about the human side of you. What makes you take what’s driving you from day to day?

Rich Yang

Thank you. It’s very personal as well for me; it relates to the impact of growing up. They’ve had very close best friends, personal friends, and family all in this fight against diabetes. It is probably the most dynamic chronic disease, and there are so many facets to it that not one thing can provide support and relief for the day-to-day management of diabetes. It’s just such a huge global pandemic. It’s probably the first real disruptive pandemic that continues to grow around the world. The commitment has been a lifelong passion for not only me but everybody here. The many former colleagues I worked alongside at Medtronic in diabetes continue to fight in this space, but bringing innovation to the masses has been difficult. Any time you work on something worthwhile, the vast majority of the time it will be orthogonal ideas and concepts that nobody’s ever done before. It takes not only tremendous patience, and I’d say perseverance, but a certain type of person and a team that could withstand the nuances of taking innovation to market. It is not the fast journey, especially in diabetes, but the amount of investment time and resources in invention to bring something orthogonal to market. As in diabetes specifically, 99.9% of the companies that are pursuing continuous sensing have not made it to the finish line in the last ten years. Regardless of how much money has been thrown at it, it’s an incredibly difficult problem to solve. We never lose sight of bringing innovation to the masses. Global health equity is something that we continue to chase after we’re not done until everybody who can benefit from a sensor has access to it, so we still have a long way to go. 20 years of sensing haven’t been nearly enough. So for you, for introducing me and teaching me about the diabetes world and the impact we can make on many others who have mentored me and the many peers that I’ve worked alongside, this is a horrible disease. We’re finally in this generation where we can beat it. So there are a lot of new technologies on the horizon, and we won’t stop until we get them in the hands of everybody who needs them.

William Hsu, MD

I love it. 38 million people battle against diabetes on an everyday basis. We, together, are people coming from all walks of life, even from the technology side, offering hope and new solutions. People for people living with Type 2 diabetes. Rich, I want to thank you for the time you spent with us.

Rich Yang

Thanks, Will. It is always a privilege, and I thank you for your time. Have a great holiday weekend ahead.