Is a functional cure for Type 1 Diabetes on the horizon?
It’s 1920. You find yourself desperately thirsty. You’re making frequent trips to the bathroom and you’re basically wasting away. You go to your doctor and he tells you that you have high levels of sugar in your urine.
Then he gives you a dire diagnosis; you have diabetes mellitus, or Type I diabetes, as we call it today. In Greek, mellitus means “sweet,” but back then there was nothing sweet about this diagnosis. It was a death sentence.
Type I diabetes is an autoimmune disease that results in the destruction of a cell called the beta cell that resides in the pancreas. The beta cell is part of a cell structure called the islets of Langerhans and it is responsible for producing insulin.
Many of you have probably heard about insulin. It’s a very critical hormone that is responsible for regulating your blood sugar levels. Those blood sugar levels must be kept within a very narrow range for good health and life.
Then there is Type II, which you’ve probably heard about. There are many more patients out there with Type II diabetes, but that tends to be a lifestyle disease. Not always, but it tends to be. In contrast, Type I diabetes hits basically without warning, young and old, and once it’s established it’s a lifelong disease.
A hundred years ago, that life was heartbreakingly short. What I show here is a child with Type I diabetes back then. A child usually died within one year after diagnosis. Adults, maybe two years or a little bit longer.
This all changed in 1921, when two Canadian physician scientists by the names of Dr. Frederick Banting and his then student assistant Charles Best isolated insulin from the pancreases of dogs and showed that that insulin was able to control the blood sugar levels. This important groundbreaking discovery led to a Nobel Prize for Dr. Banting, but also quickly led to the use of insulin in humans. This changed Type I diabetes from a fatal disease to a chronic disease.
Here we now see that same child just two months after starting a therapy with insulin. You can see a remarkable recovery.
The use of insulin was historic and momentous, the discovery and the use of it, but it still was not a cure. Not even close. It really changed a death sentence to a life sentence. Patients with Type I diabetes still had a chronic disease that they had to continuously manage in order to control it. To survive, these patients have to monitor and control their diet, track their physical activity, measure their blood sugar levels throughout the day, and then choose the right amount of insulin to inject throughout the day to maintain that blood sugar level.
Fast forward to today, a hundred years later, we really haven’t changed the way we treat this disease. We’re still basically doing the same thing. We’ve gotten better. We have better ways of measuring the blood sugar levels. We have better insulins. We have better methods to administer it, more convenient methods to administer it. At the end of the day, we’re still doing exactly the same thing. We’re injecting insulin and trying to get it just right.
What I’m going to show you is to really give you a feel for what it means to be a Type I diabetic. What I have here, what I’m going to dump out here, represents all of the injections that a Type I diabetic has to take throughout a year. Keep in mind this is a lifelong disease, so multiply this by decades. Add to this the constant threat of getting the insulin dosage wrong, and that can lead to life threatening bouts of low blood sugar. You can see that Type I diabetes has a major impact on the quality of life.
Let’s watch a video of a caregiver talking about that impact, the day to day struggle with Type I diabetes.
It’s a fatal disease. I call it spending your life not dying.
I think that’s such a strong statement; spending your life not dying. That really is what it’s like. Patients will tell you that barely a moment passes by during the day that they don’t think about this disease. It’s especially hard on loved ones, especially parents of children with Type I diabetes. You can imagine trying to inject your child with this insulin on a regular basis.
The day to day impact of this disease is bad enough, but to add insult to injury, or in this case injury to insult, even with very careful management, Type I diabetes exacts a heavy toll in the form of long-term complications. This includes heart disease, stroke, blindness, kidney disease, foot ulcers, and even amputation due to vascular disease. Sadly, the life expectancy for a patient that has Type I diabetes is decreased by an average of a decade or more.
Patients need a cure. In fact, they’re desperate for a cure. Let’s listen to a video of a patient that is enrolled in a clinical trial that my company is running right now talk about what a cure means to him.
You spend your entire life wishing for one thing above all else. If someone said, “We’ll give you $50,000,000 or the cure for diabetes,” I wouldn’t have to think about it. I can tell you right now it would be the cure.
The introduction of insulin was not only important for managing the disease, it also gave us critical insights into the underlying cause. This is very important. Combining this, understanding the basic research, the base knowledge of the disease with breakthrough technology is what will get us to a cure. That combination is often called translational research or translational medicine.
The promise of translational research has been a real driving force in my career as a scientist. It prompted me to leave academia about 30 years ago to become one of the pioneering people in the biotechnology industry and founding one of the early biotechnology companies here in San Diego.
Those were really exciting times. We were working on the forefront of new fields, interacting with the best and brightest throughout the areas, and I really found it intoxicating. I went on to become a founder of a number of other biotechnology companies here in town.
However, it’s not always easy. Being on the cutting edge seldom is. I can give you an example. One company I was a founder of, which was called Viagene, was one of the early first gene therapy companies. Gene therapy is a tremendously exciting technology, but we were way ahead of our time. Gene therapy just got to its first product approval last year by another company, a full 25 years after we started Viagene.
Six years ago, I was presented another opportunity to push the boundaries of science and medicine. A recruiter called me and told me a compelling story about a local company called ViaCyte. ViaCyte’s mission was nothing short of delivering a cure for Type I diabetes using a pioneering regenerative medicine approach. I was intrigued. This was an opportunity to not just work on a treatment, which is what we often do in my industry, but actually to deliver a cure, something that is pretty rare.
After meeting with the dedicated and talented team at ViaCyte, I found the work that they were doing, the decade or more that they had spent on the pioneering work, was very convincing. It led me to join, for the first time, a company and run a company that I hadn’t actually started.
How are we going to deliver a cure? If you recall, I said that the problem with Type I diabetes is the autoimmune destruction of beta cell. If the problem is a loss of a beta cell, then maybe we can cure that problem with a replacement cell.
As it turns out, about 18 years ago another amazing Canadian physician scientist by the name of Dr. James Shapiro showed the world that a cure for Type I diabetes is indeed possible by replacing that missing cell. What Dr. Shapiro and his team did was they isolated islet tissue including beta cells from pancreases taken from human cadavers. They infused that islet tissue into the liver of patients with Type I diabetes.
Excitingly, many of these cells will take up residence and be able to produce insulin in normal fashion and correct the disease. In fact, these patients who received cadaver islet transplants, now most of them will go for five years or longer completely insulin independent, essentially functionally cured.
That was very exciting. However, cadaver islet transplant has its own set of severe limitations. The biggest limitation is just a shortage of cells. This has to come from pancreases taken from cadavers. In the U.S., believe it or not, there’s only about 1,500 pancreases available each year that would be suitable.
Also, these patients have to take continuous immunosuppression and it’s very costly. As a result of these limitations, while there are millions of people out there that have Type I diabetes, only approximately 2,000 patients have been treated with cadaver islets in the last 20 years.
Our ambitious goal is to overcome all of these limitations and make a cure available for all patients. We have a lot of help on this. We work with the California Institute of Regenerative Medicine, we work with JDRF, which was formerly known as Juvenile Diabetes Research Foundation, clinical investigators, and importantly with amazing patient volunteers. We’re on a path to make this cure happen.
To tackle the issue of supply, we are using another emerging exciting technology that you actually heard a little bit about earlier, which is the use of an embryonic stem cell line. Embryonic stem cells have the unique capability of being able to transform into any cell in the body. Moreover, these cells are essentially immortal, meaning that a single cell line that we have banked gives us sufficient material to produce replacements cells for essentially all patients.
By discovering how an embryonic stem cell naturally becomes a beta cell, our scientists developed methods to drive these cells to become pancreatic progenitor cells that we then implant into a subject and those cells further mature to produce insulin and other factors from the normal human islet and correct the disease. That may sound relatively straightforward, but this slide here represents about 10 years of work and a couple hundred issued patents that came as a result of it.
Having the cells is important, but it’s only part of the challenge. We also need a way to conveniently, safely, and effectively deliver these cells to the patient. For that, we developed a device technology, basically a device that we could fill with these cells, implant under the skin, and then those cells would mature in the device and begin producing the insulin and other factors.
However, we wanted more than just delivery. We also want to protect these cells from immune rejection so that we can eliminate the need for immunosuppression. Thus, was born the Encaptra cell delivery device.
The device has a semipermeable membrane that traps the cells inside. The membrane allows the passage of insulin and other protein hormones back into the bloodstream. You can think of this like a tea bag. The cells we put inside are like the tea leaves and the insulin is the tea essence that is coming out. The membrane provides a barrier against the patient’s immune system, and therefore protects these cells from immune rejection and eliminates the need for immunosuppression.
The cells and the device together make up a product candidate that we call PEC-Encap. PEC-Encap has been tested in animal models that have Type I diabetes and shown to be very effective. In fact, when we take these human cells and we put them into an animal, we essentially humanize that animal in terms of its blood sugar regulation, meaning that animal will now regulate its blood sugar to the human set point rather than the normal set point of that animal, so it’s very effective in those models.
We’ve now moved on to testing this product candidate in patients with Type I diabetes, a big step forward for any program. It’s early days and it’s certainly too soon for us to claim victory over Type I. However, should we be successful, and I believe we will be, then almost exactly 100 years after Type I diabetes went from a fatal disease to a chronic disease, we’ll deliver the next big step, a functional cure that can be used by all patients with the disease.
What this means is when we’re successful, instead of the daily grind of trying to inject insulin and keep that blood sugar under control and prevent those long-term complications, a patient will receive a dose of stem cell derived islets in a device placed under the skin that could last for years. That means we go from this big pile of syringes you see here to essentially a device that looks like this.
This is actually the Encaptra cell delivery device that would be filled with the cells and implanted under the skin. A big difference.
The regenerative medicine approach that we’re pioneering at our company has tremendous potential. Not just for diabetes, but for many other diseases. Our goal right now, though, is to prove that potential by delivering a functional cure to all patients with diabetes. We share a goal of JDRF. We want to live in a world where Type I goes to Type None.