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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
Glucose is essential for life, and the insulin we produce is designed to leave just the right amount in our bodies for healthy functioning. Thus, when we under produce insulin or we over produce it, the results can be devastating. Nevan Charles Elam is the founder and CEO of Resolute. Nevan, welcome to Tech Nation.
Dr. Nevan Charles:Hi, Moira. Thank you for having me.
Dr. Moira Gunn:Now we're gonna talk about 2 different drugs today, and I mean 2 very different drugs for 2 different patient populations, but they're both addressing conditions which occur when a single normal body function goes awry. So let's start there. What function in a healthy body are we talking about? And of the many things that can happen, what 2 different ways can they go awry?
Dr. Nevan Charles:What we're really talking about, in this case is glucose. And glucose is, of course, derived from everything that we eat. And how it can go awry is we can either have too much glucose in our body or, in some rare conditions, we can have too little glucose, which then starves the body of energy. And so at Resolute, we are working on 2 different programs on opposite ends of this glucose problem. In the case of too much in the case of too much glucose, it's really diabetes.
Dr. Nevan Charles:And I think as we all know, diabetes is an epidemic in the US. And the problem persists throughout the body with too much glucose as the vasculature is corrupted. Whether if you think about the extremities and things like foot ulcers or if you think about kidney problems, and also your vision. So it turns out that with that corruption of the with the glucose making your blood vessels very leaky, it even happens at the back of the eye. And initially what happens is fluid leaks into the retina and then into your central vision leading to blurry vision, floaters, and if left untreated, blindness.
Dr. Nevan Charles:In fact, diabetes associated eye conditions are the leading cause of blindness in the US today and elsewhere. On the opposite end of the spectrum, there can be the underproduction of glucose in very rare conditions where insulin is overproduced. So if the body overproduces insulin, it tells your cells, liver, fat, and muscle, to uptake all of the available glucose. And, unfortunately, that starves the brain of glucose. And the brain necessarily uses a lot of glucose.
Dr. Nevan Charles:In fact, up to 50% or more of our glucose is used by the brain. In these rare conditions, often they begin at birth and can lead to not just brain damage, but if left untreated can lead to stroke and eventually death. A very, very serious, condition that we see in childhood.
Dr. Moira Gunn:Now the pediatric condition, this is called congenital hyperinsulinism. What is that like for the family?
Dr. Nevan Charles:Yeah. Congenital hyperinsulinism, this rare condition which affects single digit thousands of children, as well as in Europe and and the US. In some cases in the world, it's it's higher. But this is a nightmare disease. If you can imagine as a parent where 24 hours a day from birth, you are obsessed with making sure that your child has enough available glucose.
Dr. Nevan Charles:Meaning, you're constantly feeding, using intervention with dextrose or glucose to hopefully keep your child's blood sugar levels above the normal range. And invariably, it leads to a lot of difficulties, particularly overnight. So it's not just checking during the day, checking at school, but 2 in the morning, 4 in the morning, 6 in the morning. And unfortunately, we don't really have a therapy that's been developed to treat this disease. And that's led to a lot of complications for physicians and of course as well as the families.
Dr. Moira Gunn:Well, let's start with the diabetic eye condition. It's called DME, diabetic macular edema. What is the current treatment for that and and what are you doing there?
Dr. Nevan Charles:So for, diabetic related eye conditions, and in particular diabetic macular edema, over the last 50 years there's really been a couple of options. Back in the 1970s, we used lasers. And those have largely been replaced by injecting different therapies directly into the eye. And in particular, in the last 15 to 20 years, these therapies are used monthly as the gold standard to be able to get the necessary medicine into the patient's eye. And given the painful route of administration, I think it Because what happens is the gold standard is monthly injections, but often physicians and patients will stagger their injections.
Dr. Nevan Charles:And that then leads to to bad outcomes. In addition, it turns out that these injections are only active or only work in about 50% of the patients that are actually suffering with DME.
Dr. Moira Gunn:Now what are you doing?
Dr. Nevan Charles:And so what we've done here at Resolute is we've taken a very different approach. We've taken approach that looks at the body really holistically And we, given that it is diabetes and what's happening throughout the entire body is that corruption of the vasculature. And we believe that a systemic approach is the the right approach to bathe the entire system with a therapy, including at the back of the eye, to be able to stop that leakage and, prevent it in the future. So that's led for us led us to develop an oral therapy. So we have a once daily tablet that we believe is a very different pathway than the injections into the eye that has the potential to be highly effective in patients.
Dr. Moira Gunn:Now you've just started a new phase 2 global trial. I know it's in in Europe and in the US. Tell us about that trial. How many patients are you looking at? What are you doing?
Dr. Moira Gunn:How does it work?
Dr. Nevan Charles:Yeah. We recently began, at the end of 2022, a phase 2 study in the US looking at a 100 patients at about 25 different sites, including sites with some of the key opinion leaders, retinal specialists. And we're studying 3 different dose levels in a placebo controlled study where we wanna see with patients that are newly diagnosed with diabetic macular edema, Whether our tablet will be effective over 3 months of daily dosing at reducing that swelling that we see that occurs in the eye, as well as seeing some improvement in vision. The study itself will go throughout 2023, and we expect to be able to announce the results in the Q1 of 2024.
Dr. Moira Gunn:Now you're saying systemic, you know. You take a pill, yes, it goes to your whole system. What does it do that just taking your insulin and lowering your blood sugar doesn't do? And and where does it do it all over the system?
Dr. Nevan Charles:So our oral therapy is really looking to reduce the inflammatory response. And what happens when you have diabetes is there's a massive inflammatory response throughout the body. Sometimes that can be helpful. But when it's overactivated, it's not helpful and can lead to destruction of your blood vessels and cause other conditions. And so our therapy actually tamps down that response such that the inflammatory response is reduced, allows for more normal functioning of your blood vessels, and, allows for improved vision and the reduction in swelling.
Dr. Moira Gunn:But this is true throughout your body. Could it possibly help other conditions associated here?
Dr. Nevan Charles:That's a great point Moira. And we are looking at a few things in this initial study, but that's beyond the scope of our study for the eye. But definitely a point of curiosity given the other challenges and complications that patients with diabetes suffer from. There may be some other benefits and over time as we continue clinical studies, we'll definitely be looking at that.
Dr. Moira Gunn:Now let's quickly go to the other drug, the one that treats the pediatric conditions. I understand you're beginning phase 3 clinical trials now. Tell us what you're doing there.
Dr. Nevan Charles:Yes, we are. We plan to initiate phase 3 studies for congenital hyperinsulinism with our antibody therapy mid this year in 2023. And this is really to dose children for a longer period of time, to see whether we can control their glucose levels as we've saw in earlier clinical studies. But in phase 3, of course, in the most robust environment. And so we anticipate dosing these children over a series of months and then, again, measuring their glucose.
Dr. Nevan Charles:And if we achieve the results that we've seen in prior studies, we believe it can lead to an approval for the therapy. And finally, most importantly, a chance for, you know, the children and these families to have something that's effective, that can really change and impact their lives. We've heard just anecdotally from patients and their families of the changes that they've experienced when they've been on the therapy. Things like my child never had an appetite and woke up hungry. My child slept through the night.
Dr. Nevan Charles:These types of soft outcomes are very important in addition to just looking at their glucose values because this really is a psychosocial issue for these children and for their families and caregiver caregivers. Now that
Dr. Moira Gunn:anecdotal evidence was coming from your phase 2 study, I presume. That's absolutely correct. And, you know, we hope to replicate those
Dr. Nevan Charles:results, and and even a greater number of patients in in a robust study fashion that would justify approval of the therapy.
Dr. Moira Gunn:Now how do you take this therapy? Because after all, it's hard hard to get a a baby to take a pill as an example. How do you get this antibody in?
Dr. Nevan Charles:Absolutely. Definitely, a a pill wouldn't work here. And for this for this therapy, it's actually a 30 minute infusion, that we actually deliver. And so if you as you can imagine, in the hospital, when these patients are most vulnerable, that is particularly useful because you know you're getting the drug into, the child. And then past that as the child gets older, there's the maintenance therapy that they would take for the 30 minute infusion.
Dr. Moira Gunn:So you anticipate having to provide this perhaps over their lifetime?
Dr. Nevan Charles:You know, it it depends on the on the child. We we kind of think of the therapy as for about 15 to 18 years. It could be more. It could be less. No one really knows biologically what happens, but these children are overproducing insulin.
Dr. Nevan Charles:And as a result of, you know, at least a dozen or more genetic causes, and the pancreas just may burn itself out by producing all of this insulin such that at some point whether the individual's 18 or 20 or 30 years of age, the insulin is not overproduced and they can resume a more normal life. So we've seen cases where a child may be, you know, preteen and it may resolve. We also know that there are individuals who are in their forties or fifties that still have out of control hyperglycemia.
Dr. Moira Gunn:Back to the diabetes, I'm struck by the fact that one out of 10 Americans have diabetes. And seniors, 1 out of 3. 1,000,000 and millions of Americans, and I'm not even talking about across the world, many of these Americans, as I understand it, are either undiagnosed or lack the resources, or accessibility to medical care, which in itself can lead to blindness, and yet your diabetic eye treatment is a new drug. New drugs are expensive. You know, they have you have to pay for the clinical trials.
Dr. Moira Gunn:You have to pay for all of these things. How are these drugs going to get to the people who need them at a price that they can afford?
Dr. Nevan Charles:It's a great point, Laura, and completely agree with you with respect to, you know, really the problem in diabetes. Where if you take individuals who have high blood sugars, and are trending towards diabetes, as well as those with full blown diabetes, it's about 40% of the US population which is staggering. And of that, we know that about 1,500,000 have very serious eye disease, eye complications as a result with their diabetes. And drug development is definitely expensive and I think every pharmaceutical company will acknowledge that. However, here we have a true paradigm shift.
Dr. Nevan Charles:Today, we have a treatment, the injections into the eye, that have to be done by a retinal specialist at a specialized center involving very highly trained individuals. You have a patient that comes in and for at least 10 to 12 hours of the day, they're out of commission after that injection, which is often very painful. Often that means that someone has to bring them to the clinic for that injection. So there is a cost or a burden that is very significant in the overall health care system as well as in productivity. With an oral therapy, it's a complete shift in the way we think about it.
Dr. Nevan Charles:Because an oral therapy will be much cheaper than what we would experience today with the injections into the eye. It does not require a specialist. You can take a pill anywhere. And that's what had us push to actually drive and develop this therapy and to get it into the clinic. Because it's not just a question of convenience or compliance, but it's really a question of access.
Dr. Nevan Charles:So when we think about the population in the US and beyond, there's a massive underserved population which disproportionately suffer with diabetes and as a consequence with diabetic macular edema. And we wanna make sure all of those patients can actually get that therapy. And what we know today is that it's very challenging to get retinal specialists into certain areas that are underserved, and to be able to deliver that therapy and for those patients to be willing to actually endure the injections into the eye. In fact, our head of ophthalmological development here at Resolute has started, something called Retina Global, which is a nonprofit, which he and other retinal specialists travel, both in the US as well as all over the world, to try to deliver therapies. And what has him excited, as well as I think all of us, is if we actually envision a tablet that any patient could take, that drastically improves the landscape and the potential to protect vision for these patients.
Dr. Moira Gunn:So the very idea that it's a pill that doesn't need to be refrigerated, that could be produced again and again and again, that can be sent anywhere, that is self administered, it's the it's that's the nature of a pill, it's self administered. That brings the cost way way down. Is that where we're going here?
Dr. Nevan Charles:That's exactly right, Moira. And it's the opposite, I think, of the story that we usually think of with pharmaceutical companies. I think a lot of us in the US and worldwide think of just the massive profits that pharmaceutical companies derive. But in fact, there can be true innovation, which not only change the paradigm and improves outcomes, but reduce the overall financial burden on the health care system. And we believe that our therapy here actually has that potential.
Dr. Moira Gunn:Now finally, I have to tell you that I read a lot of biotech websites, And I mentioned that to you earlier in the pre interview. And I tell you that I don't understand a lot of what I'm reading. It's just like, what is all this and all these biotech websites? Well, I understood yours. I couldn't believe it.
Dr. Moira Gunn:And I mentioned it to you and you said, oh, that's no surprise. We use the aunt Margaret and uncle Fred rule. Okay. What's the aunt Margaret and uncle Fred rule?
Dr. Nevan Charles:Yes. The the the magic rule in science or really in anything, whether you're talking about quantum computing, anything complex, the human body, enzymes and proteins and pathways, the rule is very simple. And, the rule I have with the physicians that work on the team as well as the scientists is that you have to be able to explain the biology and explain what we're doing in a way that aunt Margaret and uncle Fred with a basic high school education like most of us have can understand exactly what you're talking about. And so it leads to a lot of iterations for whether it's on slides, on the language we use on the website, as well, as in general for presentations. And so I think we pride ourselves on being able to effectively communicate, otherwise very complex ideas.
Dr. Moira Gunn:Well, Nevan, thank you so much for joining me. I I hope you come back and keep us updated.
Dr. Nevan Charles:Maura, thank you very much for for having me and enjoy having the opportunity to share a little bit about what we're doing at Resolute.
Dr. Moira Gunn:Nevan Charles Elam is the founder and CEO of Resolute. More information is available at resolutebio.com. That's resolute with a z. Rezolutebio.com.