We interviewed George Szewczyk, President and CEO of BioKierx, a company developing a technology that encapsulates nutrients, and delivering them to the colon.
Mr. Szewczyk is an accomplished leader in the field of diabetes with years of experience. BioKier has developed a very innovative approach to diabetes by way of medical food similarly to the way bariatric surgery spurs a metabolic effect.
Mr. Szewczyk was interviewed by OneMed Sentinel editor-in-chief, Brett Johnson.
Read below for a transcript of Mr. Szewczyk’s discussion on the latest updates in BioKier’s and their plan to restore secretion of GLP hormones in diabetic patients.
Brett Johnson: Today I am with George Szewczyk, PhD. He is the Chief Executive of BioKier, a Chapel Hill, North Carolina company that has developed a very innovative approach to dealing with glucose management in diabetes patients who may benefit from this approach. Thanks for joining us today, George.
George Szewczyk: Thank you for taking the time to talk more about this company, Brett.
BJ: First, can you start us off by explaining: what does BioKier do?
GS: BioKier is a small biotech company based in NC. We are developing non-prescription product called medical food intended for people with metabolic syndrome who may benefit from it in addition to regularly prescribed medicine, . This product will mimic the mechanism by which bariatric surgery is helps people with different metabolic diseases, like diabetes, obesity, and so forth. We have been able to capture the mechanism of the bariatric surgery, which is now called, metabolic surgery, , and put this in a pill. The product is intended for people who have a problem managing their glucose, despite applying diet and exercise along with prescriptions. Note that it is not intended to treat or prevent diabetes, but rather, it is intended to help patients manage their glucose.
BJ: How does it work?
GS: The idea we have developed based on thorough analysis of bariatric surgery metabolic effect, is that we believe that the surgery, specifically gastric bypass, which is characterized by a technology that changes the way the food and digestive juices travel through the gut, One part of the gut handles food only and the other part of the gut is handling only digestive juices, and they meet up much lower in the small intestine than normally in person pre-surgery and digestion happens closer to the terminal part of the small intestine and that is delivering common nutrients present in food into the colon. We put forth a hypothesis and we have created intellectual property around it – saying that if one will be able to deliver, using specific formulation, those nutrients, which are known to be very effective in secreting GLP-1 from the endocrine cells, this can be a way of mimicking metabolic effects and psychological effects of gastric bypass surgery.
The reason I mention GLP-1 is because it is one of the gut hormones that was determined quite a while ago, that plays a very important role in managing glucose, triglycerides and other physiological effects associated with metabolic health. It was also determined that secretion of GLP-1 after a meal, which is impaired or missing in people who have a metabolic disease like diabetes, or are very obese, is associated with the disease state (4:09),. There are two approaches effective in treatment of diabetes based on GLP-1. First one prevents breakdown of endogenous GLP-1 by use of enzyme inhibitors (represented by Januvia) and another use metabolically stable injectable analogs of GLP-1 (represented by Victoza). Annual sales of both type of drugs exceeds $10B.
This was the hypothesis behind the formation of BioKier and all the research we have been doing for over eight years now. Instead of doing bariatric surgery, we encapsulate these very important nutrients, and by using specific formulations delivering them to the colon. The result you see is the same effects one would notice after bariatric surgery, which is restoration of secretion of gut hormone GLP-1, which stands for glucagon-like peptide-1, and secretion of this hormone is a very important component of restoration of proper metabolic health, including much better handling of the glucose.
So, in short, we have identified mechanism by which bariatric, or metabolic surgery restores one’s metabolic health. We have created IP around this idea.
We have developed and manufactured capsules designed to delivered, in a sustained fashion, very important nutrients. We are utilizing glutamine, which turns out to be the most effective of all the nutrients contained in fruit that results in the secretion of GLP-1. In delivering GLP-1 to the colon, causing restoration of GLP-1 secretion. We have conducted various preclinical, single dose and repeated dose studies in diabetic rats validating our hypothesis.
We have conducted a series of single dose studies in diabetic patients, demonstrating, as expected, targeted delivery of glutamine to the colon, restores secretion of GLP-1 in those diabetic patients. Right now, we are on the verge of initiating a study at Pennington Biomedical Research Center in Baton Rouge, Louisiana. We will be testing the effect of repeated dosing those capsules on restoration of good glucose control.
We will be using a device called Continuous Glucose Monitoring System. We will be measuring glucose for the duration of the study, and our expectation is that we will see a very robust lowering of averageglucose and also a reduction in glucose viability, which is another symptom of metabolic disease – unstable levels of glucose. We are hoping to provide proof of concept for our product. And, as I mentioned, currently, our plan is to initiate clinical studies towards the end of September or the beginning of October. Our plan is, based on the pace of recruitment, to complete our study sometime in May 2018.
BJ: How big of a study will it be? How will you go about implementing it?
GS: We have used a lot of our KOLs with helping us design it. Without going into too much detail, there are a lot of aspects involved in planning a clinical trial. In order to have a study designed in a way that takes into account all of the confounding factors. We are doing a four week study of dosing for each patient. We will have three groups of patients. Each group will have fifteen subjects. One group will be a placebo, another will be dosed with a single capsule for four weeks and one group will be initially dosed with the placebo and then switched to the active capsules.
We are hoping that this design will answer several questions, such as what is a magnitude of the effect of the product itself in the lowering of glucose is and lowering glucose viability. We believe that this therapy will be good for more than just managing daily glucose. We are also looking at other parameters, which could show us the ability of our product to be used in other diseases. The first one that comes to mind is hypertriglyceridemia and that is why we will be measuring both fasting and postprandial triglycerides to see if this product could have the potential to act as a treatment to help patients manage their triglycerides.
Also, we will be analyzing the whole panel of the biomolecules – which are related to cardiovascular disease. While they are not considered a proof of clinical efficacy of cardiovascular disease, they will be very important indication that if we see the improvement in those biomolecules, a subsequent study could actually show the effect the product on the risk of cardiovascular disease.
Lastly, which is partially related on the level of triglycerides, but we believe that because of the physiological properties of GLP-1, which secretion will be augmented in patients treated with our product, we should be able to see improvement in such things as fatty liver disease – such as non-alcoholic fatty liver disease (NAFLD) and or non-alcoholic – Steatohepatitis (NASH both of these are now being considered as great risks to the overall health of society and causing very high costs to medical insurance.
We believe that we will be able in this study to look into not only at the primary outcome of the changes of glucose, both average and bioavailability, but also at early indications of potential applications of this product to help people’s other aspects of metabolic disease.
BJ: Is the secretion of GLP-1 broadly recognized as the critical metabolic effect that is needed in order to deal with this problem of diabetes, or are there other hypotheses and ideas? How important is GLP-1 in the overall scheme of dealing with this problem?
GS: I can answer that by discussing other approaches which are utilizing effects of this hormone, in the treatment of metabolic diseases. Currently, there are two products on the market that are based on the recognition of the important role of GLP in metabolic diseases. It is shown in a number of publications, that low secretion of GLP-1 after a meal is associated with diabetes, obesity and so forth. Other studies that have taken advantage of this critical role in glucose management and relatedly, weight management.
The first class of drugs, the DPP-4 inhibitors – those are synthetic compounds which inhibit enzymes which digest glucagon-like peptides in human plasma and tissue, where the active form turns into the inactive form. Therefore, if one would bock activity of this enzyme, to the very high extent, it would increase the level of GLP-1 and help with glucose management. An example of great success that companies had was a drug called Januvia, which is marketed by Merck. Januvia, or generic name, sitagliptin, is inhibiting the enzyme increasing plasma-level of GLP-1. A lot of physicians consider this the second line of treatment against diabetes in patients.
The second, a little bit newer, pharmacological approach to diabetes are analogs of GLP-1. GLP-1 is a human hormone and very unstable with a half-life of a couple of minutes. So, a number of companies were able to come up with a modification to the structure which made GLP analogs much more stable, and subsequently made it very important and effective way of treating diabetes.
The biggest product on the market right now is called Victoza. It’s analogous to human GLP-1 peptides, distributed by Novo Nordisk. It is selling in a multibillion dollar market. As we look at the previous market, Januvia was selling for over $8B a year. There has been great commercial success, which comes only with efficacy in diabetic patients.
It turns out that the GLP-1, the second generation group of drugs based on the importance of GLP-1 – the injectable version of this, like Victoza, which was more effective that DPP-4, in restoring and creating a high level of GLP-1-like compounds in plasma. It was discovered, during treatment of diabetic patients, that higher doses of Victoza, induced weight loss. So, unlike DPP-4 inhibitors, which only were effective in lowering plasma glucose, the injectable analogs of GLP-1 in not only controlling glucose, but also in inducing weight loss.
Now, there is another drug called Saxenda, from Novo Nordisk, which is FDA-approved as a weight loss product. This shows that, while I don’t have recent data, but in excess of $10B worldwide, is being sold annually in drugs that utilizes the importance of GLP-1 for treatment of metabolic diseases. BioKier’s approach is a little bit different.
We believe that it’s more physiologically relevant, because we are not increasing the concentration of GLP-1. Our product is intended to increase, physiologically, the level of GLP-1 after the meal intake, which, as we like to say, our product will allow patients to respond as if they were non-diabetic to the meal, and therefore, help them manage glucose and possibly, other aspects of metabolic disease.
BJ: Can you give us a sense of how much prescriptions like Januvia or Victoza cost?
GS: The price is difficult to say, because there are two different prices – what companies charge pharmacy benefit manager PBMs and then the price for pharmacies charge patients, part of which is covered by insurance companies. If you don’t consider insurance, the monthly cost of oral Januvia is $500-$700. The cost of an injectable is even higher.
They are, just to give full disclose, the programs from the company coupons for patients, some kind of assistance program. Just looking from the perspective of patients with insurance that covers the drugs. It would be fair to say that most patients pay out of pocket around $70.00 per month. However, that is only if they are covered by insurance.
BJ: What will be the cost of your product?
GS: We have consultants that are highly experienced in pharma and marketing. We believe that if we price our product, the medical food, for management of glucose, in the $70.00-range, we should be able to find a sufficient number of patients willing to pay out of pocket this amount, especially if the doctor recommends the product and sees the clear benefits of using our product
BJ: is your intention to market it directly to consumers once it is approved
GS: First of all, medical foods do not need FDA approval, provided there is sufficient clinical evidence of product efficacy. Also, as I mentioned before, our product is not intended to treat to prevent diabetes – only drugs can do that.
Our product is simply intended to assist patients in better glucose management. Secondly, medical food distribution is regulated by the Orphan Drug Act by U.S. Congress and says that this product can be distributed only to patients who are under medical professional care. What that means is that we will work with the doctor and diabetes centers and demonstrate to them how beneficial it can be for glucose management. We will produce sufficient clinical data, and patients should use the product after the doctor say that the patient is under his or her supervision.
We did not invent the model. It is widely used by a number of medical food products on the market. People have developed very successful commercial models through website sales, with doctor approval. They are both very medically successful, and commercially successful.
BJ: Can you discuss the origins of the company?
GS: BioKier began with the idea developed after reading about bariatric surgery and its effect on metabolic diseases. It was also surprising to me that bariatric surgery – that is was basically developed to help people lose weight, also affects metabolic health.
Dr. Walter Pories of East Carolina University in his first study showed that while weight loss takes place only after many, many months, if not years after gastric bypass surgery, improvement in glucose levels and diabetes is achieved within a few days.
Therefore, the hypothesis that weight loss alone is responsible alone for the vast improvement in diabetes seems to be not supported by facts. Later I came across work from a scientist from the UK, Dr. Carel le Roux, who actually demonstrated that after bariatric surgery, there is a restoration of gut hormone secretion. His finding was subsequently reproduced by many different centers and widely published. It clearly showed that before bariatric surgery, obese patients do not secrete GLP-1 in response to the meal.
After the surgery, the secretion is restored. I started “digging” around the area, and it turned out, there are specific receptors in a human colon, and for that matter, animal colons, that respond to certain nutrients. For humans, the most effectively hormone secretagogue was L-glutamine. We started working with glutamine as the primary nutrient in our product.
Subsequently, we started raising money and initiated pre-clinical and clinical studies. We took a diabetic rat, and gave them food orally. In this case, we gave them glucose, and we showed there was NO secretion of gut hormones. However, when we took the same diabetic rat and infused nutrients like glutamine directly to the colon, we showed full restoration of gut hormone secretion. This is exactly what was observed in bariatric surgery.
We knew that our hypothesis worked. The presence of nutrients in the colon – especially glutamine – is essential in restoring secretion of GLP hormones in diabetic patients. I was developing the company with our partner in the UK, in Edinburg, which we worked with to develop proper formulation of our product, to deliver glutamine selectively to the colon. We subsequently signed a licensing agreement with the University College of London for the best existing colon delivery method.
BJ: You’ve received some support from venture organizations, as well as from the federal government, is that correct?
GS: Yes. As far as how the company was financed, it’s like most biotech companies. We started with friends and family. We were able to get a number of initial investors with funds to finance the first animal study that showed effectiveness of our hypothesis and later studies to show the effectiveness of the chronic treatment.
Then, we were able to secure the first couple of loans from the North Carolina Biotechnology Center, which is a great organization helping young biotech companies like BioKier to survive their hardest times to get to the next step. Our results then attracted the attention of Boston-based philanthropic venture group – Broadview Ventures, which, after thorough review and due diligence on BioKier, invested $1.3M. When they were investing, we also attracted the attention of the American Heart Association, which joined with Broadview and added another $300,000. This helped us greatly to continue our product development and continue with our preliminary study.
Also, we were lucky recipients to have qualified for the therapeutic grant from the IRS in 2010-2011. Recently, we were awarded the Small Business Research Grant from a division of the NIH called NIDDK of $1.6M to manufacture our product and conduct studies in diabetic subjects, which we are doing now to develop proof of concept of our approach to manage glucose.
BJ: Can you talk a bit about the IP and the patent situation. Have you been able to obtain patents on your product?
GS: BioKier filed patents at the beginning of 2009. Currently, our product is protected by our patent. Right now, we have five U.S.-granted patents for different aspects of our products. In a nutshell, the product is protected by three basic claims: first, we are protected as a pharmaceutical composition of nutrient in a formulation that provides sustained delivery to the colon. Actually, we have more than just glutamine, but several other nutrients also patented. Subsequently, we have protection for use of pharmaceutical composition for metabolic diseases and treatment of those metabolic diseases. We also have a specific patent granted to treat NASH disease using our approach in the U.S.
As far as the rest of the world, we have patents granted for the basic concept of treating metabolic diseases through sustained delivery of the colon of the nutrients. We have patents in all 38 countries of the European Patent Group. We also have patents in Japan, Australia, Mexico, Canada, EurAsia and Russia. As far as the other major markets, we are in the final stages of resolving it with the Chinese and Korean patent offices. According to our associates representing us there, they are very optimistic and believe we should be awarded patents in those countries as well.
We have several follow-on patents, including one attractive approach – the combination of our technology – which is the delivery of a colonic glutamine with a small amount of DPP-4 inhibitor, which prevent GLP-1 from decomposing. Our product will stimulate the release of GLP-1 into the blood circulation, and release at the same time, from the capsule, a DPP-4 inhibitor, that will provide transient protection for the hormone to increase its effectiveness. This seems to, based on our knowledge, provide two benefits: one, which is better efficacy of the product, and two, lowering of the dose, which will translate to a lower cost of goods.
We are very optimistic. As a matter of fact, that patent combination with DPP-4 that I just spoke of was granted earlier this year in Australia, EurAsia, including Russia. We are now in the closing stages in other parts of the world. We believe this will provide great value to the company – as it will increase interest, as everyone knows there are multiple ways of treating diabetes.
BJ: Is there anything you’d like to share with investors who are interested in coming in and investing in BioKier at this point?
GS: From the perspective of the stage of development of BioKier and our product, we are very close to achieving a major milestone, which one would expect would provide a great inflection point and increase company valuation as we expect positive results in the form of glucose management.
At the same time, from our perspective, the investor would be an essential part of our final steps in demonstrating product effectiveness – so both sides will be able to invest in the pre-milestone stage. Also, we do not require great investment at this stage. We are actually looking to complete all of our activities in terms of initiation of marketing with about $3M. Once the data is in, there will be additional investment needed to pay for the marketing.
Also, the one possibility is that the data will be so compelling, that we will be able to find either partners or somebody willing to license our product, which will provide instantaneous return to the investors, which would happen as quickly as 12 months. Should this not be the case, we expect that in a little over a year, we will be able to enter the market. We have developed robust marketing plan with experts in medical food and supplements and so forth. I won’t go into the details of the model but I can discuss if anybody is interested. Bottom line, within two years, we could start marketing the medical food., We have created some models of calculating potential revenue, and. it looks like because of the incredible number of potential patients using this product for glucose management and other potential indications, with minimal penetration of the market, we could be profitable, within two years.
BJ Sounds very exciting. Thanks for sharing the BioKier story with us today.
GS: Thank you, Brett.