Founding researcher tells the SciMar story

On December 8, 2018, SciMar’s early investors gathered in Winnipeg, Manitoba, for an update on the company’s scientific and business progress. Dr. Wayne Lautt—SciMar’s Founder and Chief Scientific Officer—shared the company story. Here is an edited transcript:

Dr. Wayne Lautt shares the SciMar story at a December 8, 2018, investor event.

Thank you all for being here. As you can probably guess, the SciMar story is an extremely personal story for me. It’s personal for quite a few different reasons. First, because the breakthrough science that explains the link between obesity, prediabetes, and type 2 diabetes was actually done by my research team. My research team—they’ve evolved over the years—but the aha! moment came in 1991, when the discovery was based on disproving a hypothesis that we were trying to test. But in disproving that hypothesis, we said, well there’s got to be some other explanation here, and the data’s right here before us. And it looks like there may be a hormone that none of us ever suspected.

At that point, the entire activity of the research laboratory changed—and we shifted, graduate student projects shifted. Everything just changed from that moment. Well, since 1991, we’ve had a whole team working on this project from the perspective of pure basic science. We didn’t think we were going to be curing the world of diabetes or any other such thing, we just want to know, how does the system work? How does the body manage all of this stuff that it has to manage? All these nutrients that we’re pouring into our body—and they’re stored for later use—how does this all happen? How is it being regulated? All of that sort of thing.

Over the years we’ve had a number of people involved including 10 different graduate students from China, Bangladesh, Manitoba, Quebec, and five students from Portugal. We set up a student exchange program with the University of Lisbon in Portugal. We’ve had a number of technicians that came and went through that course. We’ve had senior researchers coming from Ukraine, from Spain, Portugal, China, and Japan to come and work with our team. Each and every one of these people has added to the work that we’ve done; has added to the understanding of what at first seemed like a really dense tangle of facts that somehow seemed related. Some didn’t seem related. But every single person in that group contributed.

But over this whole period of time, there were two people who were there right from the start: Dallas and Karen. Dallas Legare, who started with me in 1979 at the University of Saskatchewan. It was the first time I was able to hire full-time people. And he was the least qualified person on paper of all of the people that I looked at! But what got me was the guy’s brilliance. And his enthusiasm. I could throw these ideas at him and instead of getting glazed eyes, he would ask intelligent questions. And I go, “Wow! This is okay. I can work with this guy.” Not only that, but he was building a cabin in northern Saskatchewan and I was building one there as well. So that helped a lot.

We got recruited back to Winnipeg and Dallas came with me. And the first thing we did was hire an administrative assistant. You’re not supposed to do that in science. But in order to get the number of grants that we had to get over the years, and to do the paperwork for publishing, and the whole bit, we hired Karen Sanders. With all of these people that we had coming into the lab from around the world—some of them moving away from home for the first time—Karen had to take care of everybody. There were tears that she had to dry, I’m sure, and counselling that she had to provide. I’ve never once seen her get flapped or really ticked off at anybody. And surely she had reason to with me.

Two other people who had been with us came back to join the team. Dr. Helen Wang, who did her PhD with me around 1986, and Dr. Kawshik Chowdhury. He was our most recent graduate student. He was actually the fellow who showed that the metabolic beneficial effect of exercise is acting through this hormone that we discovered. Through this mechanism that we discovered—it was a big discovery.

Well, Kawshik has come back to us as well. So these people had enough faith in the science that we did, and enough belief that this will make a difference to the world, that they quit nice secure positions and came back to the lunacy of the Lautt lab. And it is kind of a nut factory sometimes. We have one new member as well— Dr. Randall Gieni. And that for now is our research team. We don’t have tens of thousands of people the way big pharma does. We don’t need them. We just need really, really smart people, and these people are. They are the best.

So it’s very personal from that perspective. It’s also personal to me because the business side of this is actually run by my family members. It was Mick’s idea to start SciMar. At one point he said: “Dad, you’re having trouble getting this idea out to the world. Why don’t we form a company and go forward and do this?” I knew he was a successful entrepreneur, so I sort of said: “Sure, give it a try.” Well, he did more than give it a try. He just exploded into activity. And anybody who knows Mick knows that exploding into activity is something that he just routinely does.

So, it was his initiative that got us going. Then, a number of years back, my son-in-law, John West joined us. He’s got a heavy background in business intelligence, the technology world of weirdness. He was actually in charge of IBM’s elite software services team, for western North America. Well, John came in. So, John and Mick, when they work together it’s really quite amazing to see the chemistry. These guys really make it work.

And then, we pulled in Melanie, my wife of many years. We got together when we were 16 years old. She thought that she had retired as a very successful lawyer, but, no, I pulled her out of retirement, and she’s been keeping us out of trouble with intellectual property filing, and all the legal mess and contracts, and all of that stuff. I don’t have to look at that, because, I have a team that is so powerful.

Now, when I say this is personal, and I say that these guys are talented, I’m not saying that because they’re my family members. I’m saying it because each one of them is absolutely bloody brilliant. They are the foundation of the business side of this company. Without them, without their energy and their abilities, this would stay as pure basic research science and be shuffled away. It would take years before this breakthrough came out.

Another reason that it’s very personal is because of the way the first level of funding was able to be raised. Mostly, it was Mick and John’s energy and contacting people that they knew personally—people they could talk to who believed in the vision and believed that there was a way that their investment could have an impact in the health of the world. Because everyone knows someone who’s got diabetes.

So this also makes it a very personal thing. There’s a group here from Dauphin, Manitoba. What a story! Talk about a Canadian story! It’s a Canadian invention, Canadian investors. Manitoba. From a small city, in the middle of the prairie—that’s where most of funding came from to actually launch this project.

Let me sway off into a bit of the science. Please indulge me for just a minute, and I will try to make this a reasonably clear story.

The way people normally think about diabetes has largely been as a result of Banting and Best and their discovery of insulin in 1921. Since then, we really haven’t advanced in our thinking about diabetes. It’s still currently believed that the whole story about diabetes is a decreased effect of insulin. All the diabetes drugs are developed that way, the therapeutic approaches, the diagnostics, are all done based on that.

What we found is that, in fact, there’s another hormone, that’s doing a lot of the work that everyone—including me—thought was being done by insulin. Because it’s released from the liver, we named this hormone “hepatic insulin-sensitizing substance”, or HISS for short.

What you have to understand about the relative roles of insulin and HISS, is that when we take all of this food into our body, we break it down, and we take the nutrient energy and store this energy in different sites. We partition the nutrient energy mostly into glycogen, in the large muscle mass, into heart and kidney, and there is some that’s partitioned into fat. A lean, healthy person will put most of their nutrient energy for storage into glycogen, which is later broken down into glucose, and is able to be used for energy.

It’s HISS that’s actually primarily stimulating glucose uptake into glycogen, into muscle. It selectively acts on the muscle, heart, and kidneys. HISS is only released in the fed state. HISS isn’t released in the fasted state. Probably 95% of the research was done was in the fasted state, because it’s a nice stable state. When you go into your medical clinic, they’re going to check if you’re a diabetic by measuring your fasting glucose levels. By the time your fasting glucose levels are up, you’ve had this dysfunction for quite a long time already.

So, the idea here then, is that when insulin is released by the pancreas in response to a meal, insulin triggers the release of this hormone HISS from the liver. HISS then acts on these other sites, on the skeletal muscle, heart, and kidney, and results in most of the glucose being stored as glycogen.

HISS is only released by insulin when there are two feeding signals present. Those two feeding signals come from the gut. They’re chemical signals: one is through the nerves, another one is a chemical signal that I won’t get into. Both of those signals are required. So, these are what we call synergistic signals—both of them are required. And they’re permissive signals, that is, they don’t do anything themselves. They just allow insulin to stimulate the release of HISS.

So, in the normal healthy person, following the meal, insulin is released, and these feeding signals are there. HISS is released, most of the glucose goes into muscle, everything is happy.

The problem is that HISS gets blocked by a wide range of things, including simple things like psychological or physical stress. Gee, I don’t think anyone here’s every felt stressed. By lack of physical exercise. I can see we got a room full of athletes. By sugar. Wow! That’s a great one. And, we want our animal models to become diabetic in a way that exactly represents what it does in humans. We just give them some sugar. Table sugar. Ordinary table sugar. Don’t have to give them all that much. Bam! It blocks HISS.

So, what are the consequences? Who cares? So, who cares is that, what happens now is if HISS is not being released, you’ve lost at least 50% of the firepower of insulin to stimulate glucose uptake. So, the pancreas then has to secrete a whole pile more of insulin. It will control that blood glucose, but it’s controlling it, now, by converting most of that nutrient partitioning to go into fat. And so, for one meal, if you have a lack of HISS action, you get postprandial hyperglycemia, which simply means high blood glucose levels after a meal. You get higher levels of insulin, you get higher levels of circulating fat, and HISS turns out to be a very powerful vasodilator. It sends increased blood flow to these target tissues. When HISS isn’t there, right off, the first meal that it’s not there, you’ve got cardiovascular issues. So, for one meal, it’s not such a big deal, but, when it becomes chronic, now you can start to see some accumulation of the impact. The accumulation of the impact is what we call the AMIS syndrome—the absence of meal-induced insulin sensitization.

I’m sure many of you have heard about metabolic syndrome, or syndrome X. The whole cluster of pathologies that are associated with obesity and diabetes, well, that syndrome has been named and renamed 13 different times. I’m hoping to rename it for the 14th and last time, as the AMIS syndrome. And, the reason I think we can name is for the last time, is that, these others, the metabolic syndrome is  simply indicating the symptoms. We’re indicating the cause here—the absence of HISS action.

The AMIS syndrome represents a cluster of pathologies that occur as result of the lack of HISS action. And we can draw this little curve that shows that the very first thing is the accumulation of body fat, and a lack of vascular vasodilation in all of these tissues. And, as the disease progresses, then you become a pre-diabetic, your pancreas is still able to handle a load, but it’s now converting it to fat. You’re moving in the direction of diabetes. And, as it progresses, then you get into full-stage diabetes. And you can see the vascular consequences of that. Blindness, kidney failure, the need to amputate limbs, this is all the vascular side of it.

We were studying this syndrome as pure basic research scientists. So we needed to develop new tools, because we were looking at a short-term dynamic response to a meal. So, we had to develop new methods to diagnose what was going on, to measure the metabolic effects of what was happening. We had to then develop methods. We had this hypothesis that it was the lack of this hormone HISS, that was producing this entire syndrome. So, what do you do about that? That’s your hypothesis, smarty pants. Show us how it works!

So, we had to develop ways of stimulating it to go faster and ways of inhibiting it, to slow it down. We knew what these signals were that were required in order for HISS to be released. We looked at the pure basic science of it, and asked: “What’s the chemistry of these signals. How do they work?” Well, then we designed drugs that would actually imitate those signals. Then with one pill before a meal, we were able to switch the diabetic metabolism. We can switch it right back to healthy nutrient partitioning.

Finally, the way that this story is also personal, is because it’s personal to each and every one of us. Because, one of the things that we found was that the AMIS syndrome develops slowly and progressively. It may not get to diabetes, it may not even get to obesity, but it develops slowly and progressively with aging. And we’re all aging, if we’re lucky. That’s about as personal as you can get. And, at this point, we can say that our products are designed to diagnose this situation, to diagnose AMIS early, with the very first meal. We can diagnose that. We can give a preventative that’s taken as daily supplement. We can give a pill that can restore the responses back to normal by imitating those feeding signals. And, because it can affect every one of us—that is about as personal as it gets.

With that I’ll turn it back to Mick to talk about our product pipeline.

Thank you.