Carbohydrate-based answers for diabetes, hypoxic tissue and cell death

DDNews spends some time talking to Dr. David Platt of Boston Therapeutics Inc. about carbohydrate chemistry and his company's work, and what it all means to some key areas of concern in drug discovery and healthcare

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Boston Therapeutics Inc. develops novel compounds based on complex carbohydrate chemistry, with a current emphasis on diabetes and inflammatory disease. Based on Standard & Poor’s data, the diabetes drug market is estimated to be $35 billion currently and on pace to grow to more than $58 billion by 2018. Hypoxia resulting from inflammatory disease represents a global market opportunity of $30 billion, according to Boston Therapeutics figures. DDNews discussed the company’s progress toward developing important therapeutics for these markets with its Chairman and CEO Dr. David Platt.
DDNews: First, please introduce our readers to Boston Therapeutics, how you came about, the key members of your team and where you envision your company going over the next several years.
David Platt, Ph.D.: Boston Therapeutics is a drug discovery company that was formed to develop carbohydrate-based drugs for diabetes. Our scientific advisory board chairman is Dr. Larry K. Ellingson, former chairman of the board of the American Diabetes Association; our medical director, Dr. Peter Sheehan, is an expert on diabetes and wound healing. Boston Therapeutics has developed a drug, BTI-320, to block the increase of blood sugar after meals. We expect this will be a major drug to help maintain lower blood sugar in patients with type 2 diabetes in a non-systemic way with reduced side effects. A second drug in development at the company, IPOXYN, is designed to help any medical indication associated with hypoxia or the need for oxygen as oxygen therapeutics, such as anemia, ischemia, wound healing and trauma.
DDNews: You began your professional life as a chemical engineer. How do you think this background has influenced your strategic approach to drug development?
Platt: My approach to drug development is a classical medicinal chemistry approach. First, you identify a disease indication. Second, you identify the mechanism of action to influence reduction of symptoms or blocking a mechanism of action that creates a disease. Lastly, you build a molecule to block this mechanism to influence symptoms or disease. As an organic chemist, you just build the molecule to influence and block a specific mechanism of action.
My research, performed alone and with colleagues, on galectin-3 has led to drugs being developed at four different publicly traded companies. La Jolla Pharmaceutical’s lead drug for chronic organ failure and cancer—GSC100 (formerly known as GBC590), a complex polysaccharide that has the ability to bind and block the effects of galectin-3—was developed by me in the 1990s at the first company I founded, International Gene Group. I hold a patent on this drug. Galectin Therapeutics’ two leading drugs—GM-CT-01 for cancer immunotherapy and GM-MD-02 for liver fibrosis—are also based on my work at Pro-Pharmaceuticals, and I am named on their patents. (Pro changed its name to Galectin Therapeutics.) BG Medicine Inc.’s lead product—BGM Galectin-3, a blood test to measure galectin-3 levels in blood plasma or serum for clinical use in chronic heart failure—is based on research by me and others on galectin-3. I was the first person to express the galectin-3 gene, and I named the galectin-3 receptor.
DDNews: It seems that carbohydrate chemistry is becoming more popular as a tool of drug discovery. How and why did Boston Therapeutics develop its focus in this area?
Platt: We believe that carbohydrate chemistry has advantages for a simple reason. If the receptor or an enzyme works on carbohydrates, why not design an inhibitor for the enzyme to fit the same family of substrates the enzyme is designed to digest in the first place? My background in complex carbohydrate chemistry is an advantage when it comes to designing and leading the development for the correct chemistry for the task.
DDNews: Explain the 505(b)(2) pathway and how it reduces the time, cost and risk of drug development.
Platt: If we take a drug already approved by the U.S. Food and Drug Administration and we change only the formulation for it, the designation is under 505(b)(2). It can reduce the number of patients to test in clinical trials and may reduce the overall cost of development and time to approval.
DDNews: With development efforts underway in the diabetic and hypoxia areas, both of which represent enormous potential markets, how rapidly do you foresee Boston Therapeutics moving into the clinic?
Platt: Regarding our efforts in the diabetes space, researchers have already tested our lead compound BTI-320 in patients with type 2 diabetes taking metformin and obtained positive results. In a Phase 2 clinical study conducted last year at Dartmouth-Hitchcock Medical Center, 45 percent of patients responded to BTI-320 with a 40-percent reduction of post-meal glucose in the blood. We recently signed an agreement with Patheon Inc. to manufacture pharmaceutical-grade tablets of BTI-320; this positions us well for our upcoming IND filing later this year, and our planned international Phase 3 trial for BTI-320 in 2015. Separately, I believe that in the fourth quarter of 2015, the company will be in clinical trials for IPOXYN. It depends on our funding schedule with potential investors.
DDNews: Tell us about the poster being presented at the upcoming AACE meeting in Las Vegas that focuses on assessing the molecular mechanism of action of BTI-320 (previously named PAZ-320) in relation to a-amylase, a key enzyme responsible for the breakdown of starch in the human body.
Platt: The poster presents the mechanism of action and the potential of a non-systemic approach to achieve clinical benefits close to insulin injection clinical results. As we conduct more clinical trials, our ability to demonstrate significant reduction (up to 50 percent) in postprandial glucose after meals is critical. It will establish that the non-systemic approach to blood glucose management should be part of a holistic approach to manage blood glucose—systemic and non-systemic approaches in tandem. We call BTI-320 a new class of drug: carbohydrate hydrolyzing enzyme inhibitor or CHEI.
DDNews: IPOXYN carries rechargeable iron that picks up oxygen while being 1/5000 the size of a red blood cell. Is the amount of oxygen carried equivalent? Can you describe the IPOXYN molecule and how it works?
Platt: It is equivalent to one oxygen molecule to one iron molecule. The hemoglobin part is kept intact and bound to a polysaccharide. The hemoglobin picks an oxygen molecule in the lung and carries it to tissue with low oxygen content, and the oxygen is released. The polysaccharide acts as a shield and prevents—for reasons we have not fully elucidated—the nitrogen-oxygen (NO) scavenging. This discovery may give this molecule, once approved, the ultimate potential title of the safest oxygen therapeutics or oxygen carrier without unnecessary NO binding and methemoglobin formation as was known in the past with similar technologies which tried the same.
 DDNews: Finally, could IPOXYN represent the “artificial blood” that has been pursued for many decades?
Platt: IPOXYN is not “blood” by any means. It is an “oxygen carrier” or “oxygen therapeutics” molecule. When blood is not available, it could help a person survive trauma or to invigorate tissue to reduce hypoxic conditions with reduced oxygenation that leads to necrosis or damage to living cells. Once approved by the FDA, it should not be part of blood management or artificial blood considerations, because blood contains many different things, and IPOXYN is just an oxygen carrier—nothing more.

David Platt is a chemical engineer and Ph.D. chemist and has led Boston Therapeutics since its inception in August 2009. He has also served as CEO and chairman of the board of Pro-Pharmaceuticals Inc., which is now known as Galectin Therapeutics. Dr. Platt received his doctoral degree in chemistry in 1988 from Hebrew University in Jerusalem. In 1989, Platt was a research fellow at the Weizmann Institute of Science, Rehovot, Israel, and from 1989 to 1991, he was a research fellow at the Michigan Cancer Foundation (later renamed Barbara Ann Karmanos Cancer Institute). From 1991 to 1992, Platt was a research scientist with the Department of Internal Medicine at the University of Michigan. Platt has published peer-reviewed articles and holds many patents, primarily in the field of carbohydrate chemistry. 

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