Steve Freed: Please tell us a little about yourself and this new compound, BTI320.
Dr. David Platt: My area of expertise is the recognition between carbohydrate and protein. In my previous two companies, I developed drugs for a recognition between sugar and protein. In one case, it was a protein that was important in metastasis and cancer growth. I developed a sugar (polysaccharide) as a chemotherapy or as a delivery system for chemotherapy to block the cancer, because the sugar recognized the unique receptors on the cancer cells. By doing that, the cancer shrinks, or inhibits metastasis, and (the sugar) can deliver a payload and can be a chemotherapy.
SF: Then my first question is, what is the relationship between sugar carbohydrates and cancer?
DP: This has nothing to do with sugar, as related to cancer biology. We are talking about using a polysaccharide as a way to block the receptors that recognize sugar. By blocking those receptors, you actually block, mechanistically, the growth of the tumor, or the recognition between cancer cells and metastasis. This has nothing to do with metabolism, because remember we are talking about a sugar that is a chemical structure. It has no influence on DNA, or any mechanism within the cell. This is a different approach. I am the first one to be able to afford to start that approach. There are two or three companies that, based on my technology in the field, are developing that further, as a drug. I am not a researcher in diabetes. I do not have anyone in my family who has diabetes, luckily none of my children or family members have diabetes. When I started this company (Boston Therapeutics), I figured out that I might contribute to the field by doing something which people have tried to do before, with one drug on the market called acarbose (Prandase). Acarbose recognizes an enzyme in the intestine called alpha glucosidase. If you block the enzyme, sugar is reduced by 15 percent and is not digested by the enzyme in the intestine, and less sugar is produced, simple sugar is released from polysaccharide in the food going into the blood. What I understood was that I could actually create a better mouse trap. I could design a molecule, which is much better in blocking different enzymes, not just one enzyme. The way to do that is to develop one molecule that recognizes many enzymes in the intestine, not just alpha glucosidase. Let’s say, what about a disaccharide, the maltase and sucrase, and all those enzymes in the intestines that break down disaccharide like sucrose, which is a disaccharide….
I am a crystallographer as well as a chemist. We built one molecule that can go in and block many other enzymes associated with digestion of sugars in the intestine, like sucrase, lactase, maltase, glucosidase, galactosidase, and so on. We developed that molecule, which is the BTI 320. What it shows is that we were correct. We are, right now, I think in the seventh enzyme that we have published results on that we can block, when we are doing crystallography data, publishing one by one, so we can block alpha amylase, like prendase. Now we can block maltase, which is in beer. We can block sucrase, which is in soft drinks. We can block other enzymes that block sugars in the food in the intestine. We have patients and healthy people that were in a range between 20% to 60%, and that is exactly the range of insulin. You can actually reduce the amount of sugar, like insulin, before the sugar even reaches the blood. You don’t lower blood sugar with the BTI 320. You lower the amount of sugar that goes into the blood, so what is in the blood is already low by 40%. I’ll summarize again. It is basically a better mouse trap compared to acarbose. It is non-toxic; by non-toxic, I mean there are no other side effects associated with acarbose, like gas, bloating, pain, and all kinds of different things they have on the list in the insert of the drug. It is extremely safe. We never saw any severe adverse effects in any of the patients. It is, basically, a very effective potential drug. As a consequence, we got permission, and we submitted to the FDA a functional claim as a food version of the drug on the moderate blood glucose after a meal. We called it Sugar Down.
SF: Are you proposing this is going to be a legend drug, or a nutritional product?
DP: It will be a legend drug, and a nutritional product, together, like fish oil and Lovaza. It will be a prescription drug for type 1 and type 2 diabetics. As a food supplement, it can go in many different directions, from controlling blood sugar, or can associate with weight loss, or cholesterol, or whatever. It’s for everybody, including diabetics.
SF: So this blocks the absorption of sugar going into the system. When that happens, like acarbose and miglatol, Precose and Glyset, one of the major problems was intestinal gas, because when the carbohydrates sit around in the intestines and ferment, they are going to cause gas. Are you saying that this product does not have that issue?
SF: How do you account for that, because if you are blocking the carbohydrates and the sugars, where do they go?
DP: Mechanistically, I cannot tell you, because I never did the experiment with acarbose and how that blocked the sugar, but I can tell you that, because we block more enzymes, I believe that acarbose shifts the digestion over the sugar in a certain direction in the digestion mechanism, or digestion pathway, that you create a possibility of the system, because other enzymes are not blocked, that gas can be created. While, if you block evenly the other enzymes, maybe it passes, or the structure of the sugar stays intact. As a consequence, it does not digest when it comes out. That’s the one explanation. I have others, but I think that is probably the likely explanation because the difference is enormous. You don’t have gas, period. I’m not talking about taking one tablet or a lower amount. We’re talking about taking twenty tablets at once, and you won’t have gas. We did an experiment on this in the clinic where people took six tablets. Healthy as well as sick people took four or six tablets, and there was no gas.
SF: I know that the alpha glucosidase inhibitors lowered hemoglobin A1c anywhere between a half to 0.8 percent. Have you had similar or better results?
DP: First of all, we never did A1c on BTI 320. Why? Because the statistics on Phase 1 and Phase 2 (did not include) sufficient patient numbers to measure A1c. The minimum is 400, and it takes about six months to measure that, and with reporting it can go up to a year, and then it is very expensive. We do not need to do that. The FDA recognizes an AUC, area under the curve, as a way to go to phase 3, which is 400 patients. So, we did phase 1, for safety, which is 24 patients. We did an AUC 50 patient phase 2. We showed that A1c went down, by giving them the drug, BTI 320, in a clinical trial. Once you have the AUC data, and it shows that it reduced the A1c significantly enough, you can go to A1c in phase 3 on 400 patients. That will be the pivotal trial they do in Joslin. All diabetes drugs have (to test for) safety issues for the heart and kidney. They are very expensive to develop, because you need to monitor the patients on all of the toxicity issues. We do not have that, because it is not a systemic approach, meaning it does not go into the blood stream. It doesn’t go into the system, so it is really inexpensive to do the trial. It is not very expensive, just maybe five million or ten million maximum, because we measure the A1c as a compliance issue. So, to answer the question, we need to do a AUC on the phase 1 and phase 2, and then go to a A1c, which is four hundred patients. The minimum is 360, statistically. So, it’s not practical to do the A1c on phase 2. And that’s the answer why we never did the A1c, but it’s known the connection between PPG, if you go post prandial glucose, if you lower PPG, you will lower A1c.
SF: So, you are looking to use this as a product to be used along with foods, in the preparation of the manufacture of foods to help people to not gain weight, and to get less sugar?
DP: No, our purpose is to go in steps because it’s a new approach to diabetes in general. Nobody else thought that a non-systemic approach could be so powerful. Nobody before ever showed data that would has been shown in the clinic. I am from outside the system, and I never did research in diabetes. I do only carbohydrate recognition with protein. My view is that you can actually block eighty to ninety percent of sugar. This is not a simple matter. This is the heart of the disbelief. You can actually block, we have results of sixty percent. This is a serious matter, because the thinking was that you lower blood sugar systemically, like insulin; like the other drugs. You affect mechanisms of pancreas, insulin absorption, insulin production, and kidney clearance of sugar, and all that. What about a non-systemic approach? It was not there because the knowledge in carbohydrate and how carbohydrate interacts with enzymes was not in the research. There is zero. We are the only company doing this type of research. This is not about the receptors or absorption, and it’s not about another mechanism, which people use like gelation or something. We are talking about blocking the enzyme associated with sugar digestion. This is a new approach, and a very powerful one. In this arena of the non-systemic, my team, the scientists, are collaborating at the University of Minnestota with researchers there. We come with a new view that blocking sugars, it’s like eating less sugar, basically, so less sugar goes into the blood. Then you have management of the intrinsic sugar that comes from the liver, from what you call, resting sugar, or coming from the tissues, from fat, and the liver, which needs to be blocked by an existing drug. The majority of the A1c and the influence on blood sugar, is coming from the food that people eat. My suggestion as a scientist is if we can block forty or fifty percent of the sugar that comes in, then you can manage better the sugar that exists in your system from intrinsic degradation from the liver. As a consequence, you will have better management of the blood sugar. Management of the non-systemic approach is about management of not what you eat, but how you digest the sugar. We are not dealing with the food. We are dealing with the sugar that comes with the food. It is not trying to address what food you eat. I really do not care what food you eat, but I care about the glycemic load. If you eat ice cream, you should take, for example, the maximum load you can get effectively of the inhibitor in your system. If you eat protein, there is no reason to take the inhibitor for the sugar, because there is no sugar in proteins.
SF: But eventually some of the protein does get digested into sugar over a long period of time.
DP: It’s why we don’t have hypoglycemia, at all, because we are not lowering the blood sugar. We just don’t let it go up, so there is no hypoglycemia associated with the BTI 320, which is amazing by itself. All the diabetes drugs are hypoglycemic by definition. If you take too much, you’ll get less sugar. In our case, you can take too much and nothing happens.
SF: How did you discover this molecule, and do you know actually how it is working, how it blocks the sugar? Is it by blocking the receptors?
DP: The molecule blocks the enzyme that digests the sugar. It’s nothing to do with the receptors. The enzymes in your intestines that digest sugar, like the alpha glucosidase, is a protein. We designed an inhibitor to the enzyme by doing crystallography data. Crystallography, you actually bind, you cling the enzyme to one hundred percent pure, and you try to build, or design, a molecule that blocks that enzyme. We designed a molecule that not only blocks just one enzyme, but rather many of them. It is a different type of class of drug. It’s called carbohydrate hydrolyzing enzyme inhibitor. So you have a carbohydrate hydrolyzing enzyme, which digests sugar in the intestine, and the inhibitor is carbohydrate hydrolyzing enzyme inhibitor, or CHEI. That is the class that we are creating here.
SF: Does this have anything to do with white bean extract?
DP: When you talk about extracts, you are talking about something that is a botanical mixture. I don’t know what it is, so I cannot refer to that. I’m talking in terms of one molecule of aspirin, or one molecule of Lipitor. BTI320 is one molecule. It is a design of one single molecule. This is not an extract. When people say, “Oh, I have a natural product that lowers blood sugar,” we do not lower blood sugar. We have nothing to do with actual blood sugar. We have a single molecule. You can call it “natural,” because for a food supplement, you can designate it, because it is made out of polysaccharide. Most polysaccharide, like grass, you can call “natural.” But, at the end of the day, it is a designed polysaccharide, which is a drug. It’s kind of in between “natural,” because it is a polysaccharide, and sugar can come out from several plants in one single molecule. I want to explain something else about sugar. There is no science to synthesize sugar. We only believe there are ten or twelve sugars. In our case, our molecule has about seven hundred sugars in it. You need to go backward. You cannot go forward. You cannot synthesize that, and build it up, because the complexity is huge. You can only go down, like you trim your hair. If you want to have a nice haircut, you let the hair grow, and then you trim it down. In sugar design, if you have a polysaccharide, there is no science to make polysaccharide. There is no science, period. The knowledge in polysaccharide is in its infancy. It is very, very new. It is completely a new science, polysaccharide, only a couple of years. You need to trim it down. What we are doing here is to trim it down to the right size, which is part of the patent, and all that. That is the single molecule that creates the inhibition of those enzymes.
SF: It sounds exciting. Most products never make it from phase 2 to phase 3, but since this is not digested systemically, obviously you probably have a better chance of making it. When will the phase 3 study start with the four hundred patients?
DP: I need to raise the money for that. We started partially with our affiliate in Hong Kong. They are putting the money to work with some of the patients in Hong Kong University. But, here in the U.S., I’m looking to raise more money for that in the next year. What is exciting about this whole situation is that I was the first one to show that I can actually shink tumors with a sugar…. So you can understand, I was the first one to develop that technology of using polysaccharide as a chemotherapy, and shrink tumors. This is non-toxic chemotherapy…. I’m very familiar with beginning when you do something [that] doesn’t compute (with most people). Nobody believes that you can lower forty or fifty percent of your blood sugar without using insulin.
SF: There are going to be people that say, “Well, I could eat twice as much sugar, because only half of it is going to be absorbed.”
DP: You can use dynamite to create tunnels and build train tunnels to get through a channel, or you can put dynamite and blow people up, so do not ask me about what people will do with the technology.
SF: If this comes to fruition, I can see it could be a huge product for prediabetes patients, people with A1cs of 5.7 to 6.4%.
DP: The (number you need to show) lower A1c in prediabetes, this is like ten thousand patients, because the A1c is very narrow. You are going from 6.5 to 5.5%, something like that, if you want to show prevention. But I can do A1c 9 and above, in four hundred type 2 patients, then from a statistical perspective, if I show half a percent less, I’m okay. I have a significant (change), I get a drug. If I go to pre-diabetic, which is really the place where I want to be, I need two hundred million dollars development. I just cannot do it.
SF: On your phase 3, if you can show significant reduction of A1c, there will be people waiting in line to invest in what you are doing.
DP: Exactly. To get there, I need to do the AUC, and the phase 1 and phase 2, and the predevelopment.
SF: But as soon as you get this thing going, please send me some samples, so I can eat three Big Macs instead of one!
DP: I started using it myself, and I lost weight, but that’s anecdotal.
DP: Not just one. There are others, but I’m not developing it as a weight loss product. Any product that lowers blood sugar will also have potential for weight loss. You can inject insulin and still lose weight.
SF: The main problem with acarbose and miglatol was the side effects. The doctors really didn’t understand how to use the product, to titrate it very slowly so that gas wouldn’t be an issue. I know in Europe that gas is a compliment to the chef, but here, in the United States, it’s anything but a compliment.
DP: BTI 320 soothes pain, too, by the way. It soothes pain. … And by the way, nother thing about this drug is that it is chewable, so we block, right away, the enzyme in the mouth, too. It’s not just swallowing that; it’s chewable.
SF: I would like to get some powder and make myself a key lime pie with it. I always thought that Precose was a great drug, especially when they showed it can prevent prediabetes from becoming diabetes, but the side effects took over, and the doctors just don’t prescribe it; although, if they knew how to prescribe it, and titrate it very slowly, it would have been a very effective drug. The first thing people are going to compare it to is Precose, because, in the end they both block sugar, but yours may do it differently. There are a lot of retail nutritional products, carb blockers out there, but none of them are as effective as Precose. Please keep us informed. Thank you for your time.
Dr. Platt, president from the inception of Boston Therapeutics in August 2009 through November 2010. From 2001 to February 2009, Dr. Platt was Chief Executive Officer and Chairman of the Board of Directors of Pro-Pharmaceuticals, Inc., a public company with shares traded on the NYSE Alternext US (formerly the American Stock Exchange) that he co-founded and for which he was the co-developer of their core technology. From 1995 to 2000, Dr. Platt was Chief Executive Officer and Chairman of the Board of Directors of SafeScience Inc., a Nasdaq-listed company he founded. From 1992 to 1995, Dr. Platt was the Chief Executive Officer, Chairman of the Board and a founder of International Gene Group, Inc., the predecessor company to SafeScience. Dr. Platt received a Ph.D. in Chemistry in 1988 from Hebrew University in Jerusalem. In 1989, Dr. Platt was a research fellow at the Weizmann Institute of Science, Rehovot, Israel, and from 1989 to 1991, was a research fellow at the Michigan Foundation (re-named Barbara Ann Karmanos Institute). From 1991 to 1992, Dr. Platt was a research scientist with the Department of Internal Medicine at the University of Michigan. Dr. Platt has published peer-reviewed articles and holds many patents, primarily in the field of carbohydrate chemistry.
Copyright © 2015 HIPER, LLC