The Science and Supply of GLP-1s

0:00People have no idea what's coming and how big of an innovation this is going to be. One of my earliest experiences in healthcare was my pediatrician telling my mom that I should go to Fat Camp. Specialist obesity training. They're typically missing a few things. The average one will have four hours of training at obesity in medical school. We're actually all users of GLP ones. There we go. So, GLP1 is a hormone that we all have. Obesity, a choice or a condition. While regardless of what you believe, this chronic disorder continues to impact millions of Americans, with nearly 70 % of Americans fitting the description of overweight or affected by obesity.

0:50And moreover, 55 % have canceled appointments due to the anxiety of being weighed, at least according to None Well. None Well is a company trying to rethink obesity medicine, and its founder and CEO, Brooke Boyersky -Plat, joins ACC's General Partner, Benita Agarwalla. Together, they discuss what it'll really take to change some of these statistics, and how new technologies like GLP1s fit into this mix. Brooke herself has personal experience in this domain as a former patient with obesity, having even been told by her pediatrician that she has to go to a fat camp. Now she's using that fuel to rethink obesity care herself.

1:30Now this episode was also part of our sister podcast, Raising Health's GLP1 series. And if you've been paying attention over the last year, GLP1's went from being an unassuming acronym to a familiar class of drugs that some recent studies have even pegged as many as one in eight Americans trying. The recent adoption of these drugs has also spring -ported companies like Novo Nordisk, the manufacturer of Ozempik, to the largest company in Denmark. So if you, like many others, are interested in learning more about GOP1s, make sure to tune into the rest of the series on Raising Health. You can find a link to the show or the full series in our show notes.

2:10Let's get started.

2:16Hello and welcome to Raising Health, where we explore the real challenges and enormous opportunities facing entrepreneurs who are building the future of health.

2:29I'm Olivia and I'm Chris. You're joining us for the second episode in our deep dive series on the science and supply of GLP1s. Last week we heard from Carolyn Jassick, Chief Medical Officer at Omoda Health. If you haven't listened to that one, it's a great primer on GLP1's from a clinical experience. Today, we'll hear from Brooke Boyarski Pratt, the founder and CEO of NONWAL. Next week's episode we'll be with Kronis Manolas of UPMC Health Plan on the pharmacy implications of GLP1's. Brooke talks with Vanita Agrawala, General Partner of Ace of Teen Z Bio and Health about the value of obesity -specific practitioners, patient -centric medical homes, and how she thinks the metabolic health space will evolve over time.

3:08If a patient has given a choice, they prefer a medical. And that's what we've seen with our patients. So we've seen a lot of patients leave point solutions because they say, wow, you can also do my primary care. I can occasionally see you in person. You were a real doctor who I talk to and why of a care team I know and respect. So I think that's really important, particularly as it relates to symptom management. You're listening to Raising Health from A16Z by Owen Health. I am incredibly excited to welcome to the Raising Health pod today, Brook Boyarski Pratt, founder and CEO of an incredible company called Knownwell that we've had the real privilege of partnering with recently.

3:52Brooks here to join us to share a little bit about how she's looking at the obesity medicine, space as a whole, the role that she hopes Knownwell will play there, and a little bit about why she's building the company at a personal level. So, Brooke, I'd love for you to just introduce yourself and share the story behind this company. Yes, such a pleasure to be here. Thank you so much, Vanita, for having me on. I am a patient. I mean, that's really what brought me to know and well and ultimately led me to founding it. I'm someone who's been in a larger body my whole life. You know, one of my earliest experiences in healthcare was my pediatrician telling my mom that I should go to fat camp.

4:33And that really, you know, unfortunately started the process of how I viewed interacting with the healthcare system when it came to my body size. And as I got older and sort of, you know, had different educational and work opportunities, it led me to move a lot. And every time I moved and reestablished primary care, I felt like I was needing to reestablish the idea that I was a thoughtful person who took my healthcare seriously, not for any the primary care doctors I met with, they just have a lot of patients every day, and I'm sure it's frustrating for them to see so many patients struggling with the same disease state.

5:14So I was dreading going to the doctor, and it was even harder when I was actually looking for treatment for my metabolic health to find something that was accessible to me. And in my very last move, when I was walking to my new PCP for the first time, I started getting curious about if other people feel that same dread. You know, other people who were like me. And I was overwhelmed by the research, and I'll just say briefly, that was kind of the nights and weekends I started pursuing this passion of could we really create a patient -centered home for people with overweight and obesity? Well, in the venture world, you know, investors talk about founder, market, fit.

5:58and I cannot imagine a more compelling and more deeply connected founder to build a company that's going after tackling not only the bias and access and comfort issues that patients face, but also the care quality. Let's talk for just a second about your professional background, though, because it's also really interesting that while you've had that patient journey and patient connection to the obesity medicine space, you didn't come from healthcare. So you look a little different than some of our other healthcare portfolio CEOs and leaders in the healthcare space. But you're remarkably proficient, and picked it up so fast and are so compelling now, but what made you jump?

6:45You had a background in finance and consulting. Yeah, you know, very traditional kind of business background of Penn and Harvard Business School and McKinsey and worked at a commercial real estate company. So certainly not in healthcare, I joke that I'm sort of glad I didn't know what I was getting myself into when I jumped into Noanwell and creating the company. But ultimately, I had always hoped that I would one day find something to work on that I felt was my life's work. And before Noanwell, what I was always drawn to was doing a good job delivering for clients and being the best colleague and boss I could be in terms of the people I worked with.

7:25But if I'm being honest, there wasn't a day that I woke up and thought I am so passionate about commercial real estate today, right? I mean, it was just something that was important to do well and to deliver for people. But as I started, I'd always been drawn to healthcare, like just to the healthcare industry, because I always felt like how could you have a more direct impact on people than in healthcare. And I'd always joke with my physician friend that they made the right decision going into healthcare. So it almost sort of came together naturally that as I started to feel like there was an opportunity here to really touch a group that had been underserved, even though it's been a steep learning process, it sort of felt natural that I found my way to healthcare.

8:12Consider me one of your physician friends. It's very happy to have you join the forces in healthcare. Let's talk a little bit about what obesity and overweight management and medicine actually is. We've actually, we've already used the term a few times. So let's backtrack for our listeners for a second and just make sure we're all on the same page. What is obesity medicine? Like is that a specialty? What is it? It is a specialty. So if we take a step back, you know, overweight and obesity is defined by BMI. We could have a whole podcast about how that's not the best measure to use, but it's the best and sort of easiest measure we have today to diagnose the disease, right?

8:58So this is really about living in a body where your weight is higher than your height would suggest on a bell curve and that puts you in overweight and obesity. And it was not long ago. I mean, the reason Medicare, for example, doesn't cover obesity treatment is they see it as a cosmetic disease. And it wasn't long ago that that's how everyone viewed overweight in obesity. In 2012 was the first ever board certification in obesity. So that's how recently this disease state has been, you know, really viewed as something in the medical community. And obesity medicine is really about comprehensive treatment of the state of obesity and overweight.

9:42And if a person is interested in intentional weight loss, really helping them on that path, both to address the obesity and also potentially other metabolic health conditions, such as diabetes, hyperlipidemia, that can sometimes go with these diseases. So typically a clinician who practices obesity medicine is a primary care doctor from their medical school and residency days, though not always. You can see cardiologists and OB -GYN who do have a board certification in obesity. And nowadays we have fellowships, so some folks go and do an obesity medicine fellowship, and then we also have a board certification.

10:25And I'll note it's actually the fastest growing specialty in the US. And there's something called the obesity medicine association, which is the largest association of clinician to practice obesity. And we're really fortunate that my co -founder and our CMO, Angela Finch, is the president of it. So what about a primary care doctor like me, who has an overweight or obese patient who I'm really trying to figure out how to serve? to help us understand the bridge between all primary care physicians in America and the subset of physicians who are trained to deliver obesity, medicine, care, and certified to do so, given that we have a situation where over 40 % of all Americans actually fit that definition.

11:13Totally. And as we mentioned earlier, everyone's doing their best, right? So what I don't think the differences between a primary care doctor who practices and doesn't is how much they wish to help the patient. So, a PCP who doesn't have, you know, a specialist obesity training, they're typically missing a few things. The average one will have four hours of training in obesity in medical school. This is an unbelievably complicated disease, right? So, very little formal education on obesity, typically very little continuing education on the innovation that are coming on to the market. So in addition to that, which will come in fast.

11:55In addition to the education issue, though, they're also typically lacking the resources where they practice. So to practice really great obesity medicine, we also want things like dieticians, health coaches, a movement program ideally, behavioral health. And even like a good prior authorization process if you incorporate anti -obesity medications. So most primary care doctors are practicing without any of those additional services. And what they'll say to us all the time is, look, I suppose I can prescribe something. I don't even really understand the meds. I don't understand how to get them approved.

12:34And the truth is I know the patient needs more help and I don't have the services to help them. where someone who's been an obesity specialized not only has the formal education and the continuing medical education, but they are typically part of weight centers or other groups that have the wraparound services. You mentioned Dr. Fitch. That's exactly her background. She's set up weight centers in multiple places in the country, both health system affiliated and now at Knownwell, you mentioned she's president of the obesity medicine association. But if you could sort of channel her thinking, you're thinking Knownwell's thinking on this topic, what are the key pillars of comprehensive evidence -based care for patients with overweight and obesity?

13:25So there's something called weight normative medicine and weight inclusive and it's a way we practice using the broad we hear. weight normative is you should be, you know, I'm five four, you should be 150 pounds, and every time you come to the office, I'm gonna tell you you should be 150 pounds. It turned out patients actually gain more weight when they have experiences like that. The other approach is called weight inclusive, which is, hey, Brooke, I recognize you're not 150 pounds today. Let's work on the wellness goals and actions you can take inclusive of your current body size. And what's really interesting is the research suggests that that actually leads to much better health outcomes, right?

14:05So at its core is the approach around how do we work with patients. Then there are multiple pillars of the actual actions we take. So typically, though not always, an anti -obesity medication will be used, and we'll talk more about those. Typically, a nutrition program is used, either one -on -one coaching with a dietician or group classes. You want to address sleep and stress management, that could go as far as someone to undiagnose sleep apnea and could be as light of an intervention as meditation, right, and other things that we work on with patients. Ideally, you would include a movement program which we do, health coaching and remote patient monitoring, so allowing that connectedness to the clinic of having a scale at home, if you have heart disease, having a blood pressure cuff at home, a connected glucometer and working with a health coach, and lastly, really a behavioral health, right?

15:02So to the extent that a patient is interested in working on their behavioral health in addition to the other medical component, those taken together are really considered the core comprehensive program for obesity management. Amazing. And referrals to surgeries and other interventions as we call it that wrap around the medical care. The right interventions have to be matched to the right patients as with all of medicine. And I'll also note that one of the things I've learned from you all is just kind of a better awareness of how much of an adolescent problem we have as well in this country and around the world.

15:42But we've got 14 million American children and teens also living with obesity. And so this isn't just an adult medicine or an adult primary care challenge in front of us. It's really one that affects the pediatric community. that's a community that's even less trained on the whole in managing conditions and comorbidities associated with obesity and overweight. So I think it's just we have a really important opportunity ahead of us in our healthcare system to get this right, to get obesity and overweight evidence -based care right and to do it at scale. So incredibly excited about what you're building.

16:20Let's double click on one of the pillars that you mentioned, which are obesity medicines. And not a day goes by at this point where GLP ones are not headlining news stories, whether it's around cost, access, new drugs, new therapies, oral versions of the therapies, you know, anyone reading healthcare news at this point is basically inundated with GLP what are GLP ones? Yeah, you know, we're actually all users of GLP ones. There we go. In the sense of GLP one is a hormone that we all have. It has a lot of different functions, but primarily it helps with insulin regulation as we eat and consume food.

17:04It affects the speed of digestion after we eat, and it also affects the feeling of fullness, so kind of the signals that go to our brain. So what a GLP1 therapy typically is going to do is mimic the hormone that we have naturally occurring in our body. And then you'll hear about things like duel and triagonist, which is as these drugs get more advanced, they're mimicking additional hormone pathways. So simply just kind of sacking on top of each other more of the pathways that we believe impacts obesity, as well as, of course, diabetes. And what I'll mention with GLP1s and what Angela would say if she were on the phone with us, Dr.

17:47Fitch, is they've been around a really long time. The first GLP1 was approved by the FDA in 2005. So we often talk about it as if these came out of thin air, but the truth is especially endocrinologists and physicians who have been in the obesity space for a long time have been using these medications. When did you first learn about these medications and their potential? And what role did they play in your conception of impact at Knownwell? 2018 was a big year for me. Because first, it was the first time I'd ever heard about obesity medicine. I had never heard of it as a subspecialty. And I had seen a primary care doctor in Philadelphia.

18:31And she knew I was struggling with my weight. And she said, well, you should see Dr. Janine Krellos. she's a leader in the field in Philadelphia and she practices obesity medicine. And I was like, there are people who could just help me. So I saw her and she was the first person who talked about ozempic with me. And I thought it was just absolutely wild. I was like, there's an injectable and it helps with weight. Of course, at the time was being used just to treat diabetes. So that was the first time I had heard of it. Obesity medicine physicians were using it off a label at that point to treat obesity.

19:08But it's really interesting that I feel like I actually ended up hearing about it much earlier than it sort of came on to the mainstream. But it's not a surprise that people knew who knew what they were doing, knew how big of a deal it was. And I'll say when I first started talking to Dr. Fitch in 2020, when it was a little bit more getting into the public eye, She was just like people have no idea what's coming and how big of an innovation this is going to be is these get more obesity Indications approved by the FDA so she was certainly a fortune teller. Yeah, the way last data was staring us in the face and in the diabetes trials So it is all the dates you just mentioned 2018 2020 are well in advance of of kind of the current moment in time when GLP -1 receptor agonists have reached peak public awareness, but it is interesting to reflect on that that data was sort of staring us in the eyes.

20:04What maybe wasn't does obvious just because the studies hadn't been done specifically in patients who do not have diabetes, but have obesity, what was not maybe as obvious was just the role that they would play outside of diabetes specifically for the indication of weight loss. But at this point in time, they're in the arsenal. What are some of the biggest myths about GLP1 drugs? One is that there are a miracle that works for everyone. They are our most effective treatment, right? That is no question. But when you look at the data on somagletide, slash ozemic, right, 40 % of patients will lose 20 % of their body weight.

20:46So that means 60 % of patients won't lose, at, you know, 20, 20 % of their body weight. So that's a lot of folks. And the data get better as you get with newer medication. So to re -epitide is 60 % of patients lose 20 % of their body weight, which still means you have 40 % who don't. And the reason I think that's so important to call out is one, it's important you get the right medication with the right patient, which is not always a gel, who, and they may not be a responder. And the second is boy, for the patients who fall in And that 60 % or that 40%, unfortunately, they can feel like a failure.

21:20Folks who have already felt like failures at this whole time, but they're way to often times. And then when they don't turn out to be a responder, I think that's what we need to improve the education so that there isn't this shame and stigma around the disease state and the person. The second thing I would say is that there's a myth around the tolerability of these drugs. So you see a lot of PBM data and other data sets that show, you know, after one year, 40, only 40 % of people are still on the drug. And that's often used to show there's a lot of waste, you know, there's a lot of issues with the medication.

22:00First, sometimes this data, they're not always is confounded by the fact that people lose access to the medication, right, from their insurance or they move jobs or whatever. But even for the people who stay on, And what we have found in our clinic with our own research is well over 90 % of our patients stay on the medication. And we think the difference is really twofold. One, it's better understanding the patient before you put them on the medication, fall health history, family, right? Are you putting the right person on the right medication? And then the second is actively managing the symptoms of those patients.

22:36So we know exactly what to expect for certain archetypes of patients when they start a medication, whether it's phentharmonia or, you know, mongaro. So we are able to say like, hey, we expect in three days you could start to experience nausea. Actually eating small meals and making sure you start in the morning, even if you're not hungry, will help curve that nausea, right? So things you can do to really better educate the patient and actually reduce those side effects over time. So I think those are kind of two important myths. I would say there is one last one that doesn't come up quite as often, which is around food quality.

23:15A lot of times people say the food quality no longer matters. Patients can really eat whatever they want if they're on these medications because they're so effective at reducing and curbing appetite. The last thing I'd say about that is actually we have pretty good research to show that maintaining or increasing protein intake is unbelievably... It's more important on these medications. It's actually more like having had bariatric surgery. So when we work with our patients, we have such a keen focus on things like protein intake, even if that means having to supplement occasionally with a protein bar or a shake, because it can be really dangerous to the patient's long -term health to have them, you know, losing a lot of muscle mass.

23:57Especially their muscle mass. Yeah, exactly. I think sometimes that detail gets lost in the headlines, So let's come back to that 40 % of patients who even on Turs Epitide do not sort of hit the weight loss goal that They might have set jointly with their doctor. Can you just educate us on what some of the both medical and Nonmedical interventions that we might be able to offer? That subset of less responsive patients are? Absolutely. So as I first mentioned, there actually could be a medication that's better for that patient. You know, interestingly, you'll find sometimes that patients who are high responders to ventermain, by the way, a drug that's like $10 a month if you get a generic, are better or higher responders than patients for gel than that patient would be for a GLP one.

24:50Part of that we think is the biological process around what's driving the obesity that they actually respond better to different medications. So first is making sure that we're trying different medical therapies and combination therapies to see if there is a more effective medication for them. You know, ideally, actually, you're starting with that therapy and moving up to DLP ones. The second, of course, is bariatric surgery. There's a big belief in the market that bariatric surgery is going to tank. We actually, we have a little bit of a contrarian view there. We feel so many more people are finally seeking treatment that for a period of time we actually could see an increase in bariatric surgery because people are finally having these conversations with physicians.

25:36So the bariatric surgery particularly for a higher BMI individual, especially if they have a comorbidity, in today's world, maybe not with innovations 10 years down the line, but in today's world is a really effective treatment. And then there's like the things like the nutrition therapy, the behavioral health, this is such a complicated disease state. And what we found with all of our patients is there's generally not a silver bullet. So how do you work across these different modalities and really problem solve with the patient to understand what's going on? What do we know about the long -term impact of these drugs, especially in a world where so many patients are just getting on these drugs, But there exists, as you pointed out, an evidence base of patients who have been on, you know, this drug class since 2005.

26:33So what do we learn from that body of data? Yeah. So from that earlier data, which of course is what we talked about. It's going to be limited because it's certain types of patients who were who were being tested back then. They seem pretty darn safe, right? I mean, there are a few things like potential risk of thyroid cancer that have been called out from animal studies. but have never actually been replicated in human studies. When you look at real world and clinical trial data, you are not seeing an increased risk of thyroid cancer for patients who have been on the medication for a long time.

27:08Generally speaking, obviously, there are certain things that are coming out that are still being investigated like suicidal thoughts and other potential side effects that they'll certainly keep following up on. But for the best data, peer reviewed, double -minded studies that we have today, there really aren't large concerning kind of pieces of evidence that we've seen in terms of longitudinal data. In fact, it looks like cautious optimism, but it looks like some of the long -term benefits of the drug class over the longer -term horizon for patients could be quite interesting with respect to cardiovascular disease, risk with respect to treatment, potentially even reversal of fatty liver disease and stiotosis, potentially even an impact on addiction states and other behavioral health conditions.