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October 3, 2016 Issue



A Beta-cell centric Triple Combination of Metformin, an Angiotensin II Receptor Type I Blocker (ARB) and a selective Cyclooxygenase-2 Inhibitor show promise of providing Long-Term Glycemic Control for Type II Diabetes Patients



Dr. Ravi Kumar

President & Chief Executive Officer


ARKAY Therapeutics, LLC


Interview conducted by:

Lynn Fosse, Senior Editor, CEOCFO Magazine, Published - October 3, 2016


CEOCFO: Dr. Kumar, what is the idea and concept at ARKAY Therapeutics?

Dr. Kumar: Pancreatic beta-cells have an inherent capacity for compensating for insulin resistance. Pro-inflammatory signals originating from the activation of immune dysregulation, renin-angiotensin system and Cyclooxygenase-2 initiate and maintain pancreatic beta-cell inflammation which triggers insulin resistance. Progressive deterioration of beta-cell function due to inflammation compromises their inherent capacity to compensate for insulin resistance. Pro-inflammatory signals contribute to reduction in beta-cell mass which results in a state of insulin insufficiency and makes the currently marketed drugs that depend on insulin or beta-cell function ineffective. If these pro-inflammatory signals are not blocked by the right combination of drugs, beta cell function deteriorates to an irreversible state of beta-cell failure, a stage at which Type II diabetes becomes indistinguishable from Type I diabetes. The only treatment option available to patients who would have reached the state of beta-cell failure is insulin therapy. ARKAY’s pre-IND candidate, RK-01 is custom-designed and formulated to prevent or delay deterioration of beta-cell function or restore pancreatic beta-cell function to provide long-term sustainable glycemic control to Type II diabetes patients. RK-01 is an orally-active pancreatic beta-cell centric combination product and it fills clinically the most important gap that exists in the modalities used for the drugs that are currently on the market. Almost 50% of Type II diabetes patients do not meet their target goals for ABCs of diabetes care because the modalities used for the drugs on the market do not provide long-term sustainable glycemic control. The ABCs of diabetes care are A1c, blood pressure and cholesterol. I come from a family of Type II diabetes patients, I know the challenges of Type II diabetes patients, limitations of the modalities used for the drugs currently on the market and more importantly the devastating consequences of diabetes-related complications. Therefore, I founded ARKAY Therapeutics with a mission to provide long-term sustainable glycemic control to Type II diabetes patients with a patient-centric approach.  


CEOCFO: How does it work? What is the science behind your approach?

Dr. Kumar: According to a recent publication in Diabetes Care by Dr. Stan Schwartz a renowned endocrinologist, there are as many as eleven clinically relevant targeted pathways and mechanisms that contribute to hyperglycemia and systemic glucose intolerance. Progressive deterioration of pancreatic beta-cell function, reduction in beta-cell mass and consequential state of insulin insufficiency are central to these mechanisms. Activation of these mechanisms, strength and duration vary between patients based on several factors including patient-specific comorbidities. For efficient clinical management of Type II diabetes, it is necessary to block or modulate as many clinically relevant pathways as possible with DDI and adverse side effects sparing therapeutically efficacious doses of minimum number of drugs. RK-01 combines Metformin which is considered the “Gold standard” and the current standard of care with a pre-approved anti-hypertensive Angiotensin II receptor Type 1 blocker or ARB and a pre-approved selective Cyclooxygenase-2 inhibitor. Together they block as many as eight distinct yet overlapping targeted mechanisms or pathways along immune dysregulation-inflammation-insulin resistance axis that contribute to pancreatic beta-cell dysfunction and hyperglycemia. Please note that activation of renin-angiotensin system is pro-inflammatory in the context of pancreatic beta-cells and it has nothing to do with systolic blood pressure. ARKAY’s approach to treating Type II diabetes will eventually contribute to development of individualized medicines for stratified groups of patients with unique set of mechanisms and pathways that contribute to beta-cell dysfunction and hyperglycemia.  


CEOCFO: Why would those two drugs be useful in the arena that you want to use them? Why did you think that they would be or why have you seen that they would be?

Dr. Kumar: The two component pre-approved drugs that we are repurposing for the Type II diabetes space have shown efficacy in relevant preclinical animal models as well as in clinical studies performed with Type II diabetes patients. When administered alone, they improve islet morphology, inflammatory parameters, insulin sensitivity, glucose tolerance and beta-cell function. More importantly, the anti-hypertensive ARB reduced the incidence of Type II diabetes. Our expectation is that RK-01 has the potential to replace Metformin as the first line of therapy and more importantly, restore efficacy of Metformin in patients for whom Metformin mono therapy would have become ineffective or inadequate. Clinically this is very important because in spite of intense therapies with Metformin, patients experience progressive deterioration of pancreatic beta-cell function. Use of a combination product such as RK-01 makes not only clinical sense but more importantly economic sense to treat the Type II diabetes pandemic. It costs about $50-$100mm to develop a product such as RK-01 compared to over $500mm for a new chemical entity. It will be priced competitively keeping in perspective the affordability in different parts of the world. Patients with arthritis increase the risk of developing Type II diabetes by 50% and 30% of arthritis patients also suffer from Type II diabetes. There are approximately 5.6 million Type II diabetes patients with arthritis and high blood pressure. This is a patient sub population that is under-served by the drugs currently on the market. RK-01 administered at therapeutic doses will serve Type II diabetes patients in general and this specific sub population in particular.   


CEOCFO: Where are you in the development process?

Dr. Kumar: We have completed a pre-clinical proof-of-concept study in the widely used pre-clinical translational mouse model C57BL/6J diet-induced obese mice with insulin resistance and pancreatic beta-cell dysfunction in collaboration with leading CROs. In our studies, RK-01 restored or maintained efficacy metformin. When metformin was administered alone to these animals, it was ineffective due to progressive deterioration of pancreatic beta-cell function, which is something that occurs in Type II Diabetes patients as well. When metformin is administered as the first line of therapy, depending on the status of the pancreatic beta-cell function, metformin is effective for a short period of time; that lasts anywhere from three to six months. During that time the pancreatic beta-cells continue to undergo progressive deterioration in spite of intense therapies. As soon as patients reach a state of insulin insufficiency, metformin becomes ineffective, because the primary mechanisms by which metformin works is by enhancing or potentiating insulin-mediated hypoglycemic mechanisms in Type II Diabetes patients. That means metformin efficacy has an insulin dependence and patients have to maintain a certain level of glucose-induced insulin for metformin to remain efficacious. RK-01 which contains two component drugs which are anti-inflammatory in the context of beta-cells restored or maintained a state of insulin sufficiency to restore or maintain efficacy of metformin in the mouse model. RK-01 lowered non-fasting, fasting blood glucose levels and improved glucose tolerance in the oral glucose tolerance test. Study results were presented at the 76th Scientific Sessions of the American Diabetes Association held in June 2016 in New Orleans. These results will have enormous clinical significance if they translate over to Type II Diabetes patients.


CEOCFO: Over the years there have been a number of drugs for diabetes that were used and then they are taken off the market. What gives you the confidence that you are on the right track?

Dr. Kumar: That is a great question! That is a very important question! That is something that we think about all the time. I have spent over twentyfive years in the pharmaceutical industry and I am quite aware of some of the episodes that have occured with certain classes of drugs. When I founded ARKAY Therapeutics, safety was my first and foremost consideration. The proposed doses of component drugs in RK-01 have a long track record of safety for chronic use when used alone in patients with Type II Diabetes, patients with high blood pressure or hypertension and patients with arthritis. Moreover, we are not just combining the three drugs, we are also using unique modified drug release formulations to spare potential DDIs (Drug-Drug interactions) and to achieve not only therapeutic synergies but also kinetic synergies. Therefore, being aware of this and also having spent a lifetime in the pharmaceutical industry, particularly in the area of metabolic diseases, cardiovascular diseases and chronic inflammatory diseases, I have a very high level of confidence that our combination product will be safe in patients. That is indicated by the safety of our combination product in the mouse study where we administered drugs in a staggered manner to simulate modified drug release.

CEOCFO: Is the medical community aware yet or is it too early?

Dr. Kumar: Absolutely! The scientific rationale and the product concept has been endorsed by some of the leading endocrinologists. One of them is Dr. Stan Schwartz, who is a renowned endocrinologist. Dr. Schwartz is also a member of ARKAY’s Scientific Advisory Board. He has championed the concept of blocking progressive deterioration of the pancreatic beta-cells to manage Type II Diabetes clinically. Also, he is a proponent of reclassifying diabetes. Instead of just classifying diabetes as Type 1 and Type II, classify diabetes based on the status of the pancreatic beta-cells function and also the mechanisms and pathways that contributes to different states of pancreatic beta-cell function and hyperglycemia. Like me, he has also championed using the right combination of drugs early for Type II Diabetes. Instead of treating patients with just metformin alone; combine metformin with anti-inflammatory beta-cell centric combination products to allow patients to continue to take their first line of therapy during their entire lifetime, rather than starting with just Metformin alone and then three months later getting the second drug added on and then six months or a year later getting a third drug added on as recommended by American Association of Clinical Endocrinologists. What happens in the current clinical practice, during the time patients are administered metformin as the first line of therapy and other drugs are added later on as dual and triple add-on therapies, the beta-cell function would have deteriorated so much and that would put patients on a certain path to reach the state pancreatic beta-cell failure. It also puts the patients on a certain path to develop diabetes-related complications, such as retinopathy, nephropathy, neuropathy, stroke and skin ulcers. With RK-01, we expect to prevent early use of insulin and our ultimate goal is to educate patients to get diagnosed early and start taking beta-cell centric medicines as the first line of therapy and avoid taking insulin during their life time. Dr. Schwartz is a very strong supporter of ARKAY’s scientific rationale and the product concept. He is well known, lectures nationally and internationally; has published extensively in this space. He is an Associate professor emeritus from University of Pennsylvania. He is currently in private practice.


CEOCFO: Are you seeking funding or partnerships?

Dr. Kumar: Yes. So far I have been the only investor in the company, because as the founder and innovator, before I could ask others to invest in my company, I wanted to make sure that I take the risk with my money and establish the proof-of-concept, which we have accomplished already. We are considering a two-step strategy for the clinical development of RK-01. We understand that human data adds tremendous value to the animal data, therefore, we are seriously considering a small investigator-initiated human clinical study by partnering with a leading CRO preferably in the Unites States or in a foreign country with a track record for conducting high quality clinical research. Human data will make ARKAY Therapeutics very attractive to potential investors in later rounds of financing as well as potential pharma partners. Human data will enable submission of a more complete IND in the United States as well. We currently have an on-going convertible equity notes offering and we are reaching out to friends, family and high net-worth angel investors. With this instrument, we expect to raise at least $1 million this year towards reaching a critical inflection point which is generation of human data. The proceeds would pay for the generation of human data from a small clinical study and secure United States as well as international patents. After successful completion of the human proof-of-concept study by the fourth quarter of 2017, we expect ARKAY’s valuation to increase significantly. Boosted by the positive human data, we expect to raise another $25 to $30mm in 2017 and 2018 through Series A financing, Series B if necessary. The proceeds will be used for the traditional clinical development of pre-IND meeting with the FDA, formulations development, filing of an IND for RK-01, Phase I and Phase II clinical trials in the United States. After successful Phase II clinical trials, our business plan is to partner or merge with a pharmaceutical company with an established infrastructure in the Type II Diabetes space and conduct Phase III and long-term cardiovascular safety studies. Since the proposed doses of each component drug as well as some dual combinations of the component drugs in RK-01 have a track record of safety for chronic use, we don’t anticipate FDA to require long-term cardiovascular safety studies prior to approval. For more information on how RK-01 differentiates clinically and mechanistically from currently marketed drugs, bios of the management, board members, scientific advisors and find out why now is the best time to invest and partner with ARKAY Therapeutics, I invite the readers to visit our company web site:


CEOCFO: Have you filed patents?                      

Dr. Kumar: Yes, we have filed two U.S. and one international PCT patent applications with a priority date of September 9, 2014. They all have been published.


CEOCFO: What is the take away? What is the most important thing to remember about ARKAY Therapeutics and your innovation?

Dr. Kumar: ARKAY is developing an innovative pancreatic beta-cell centric combination product which fills clinically the most important gap that exists in the modalities that are used for the drugs that are currently on the market. RK-01 developed as a 505(b)(2) product with efficacy equivalent to metformin with additional benefits of reducing arthritic pain and lowering blood pressure will have exclusivity for three years and RK-01 developed as an innovative product will be disruptive with improvements in glycemic parameters, inflammatory parameters, lipid parameters and oxidative stress parameters better than Metformin alone with additional benefits of reducing arthritic pain and lowering blood pressure will have exclusivity until 2034, the expiration date of ARKAY’s patent applications.


“as the founder and innovator, before I could ask others to invest in my company, I wanted to make sure that I take the risk with my money and establish the proof-of-concept, which we have accomplished already”- Dr. Ravi Kumar


ARKAY Therapeutics, LLC



Ravi Kumar, Ph.D.

(609) 977-1857







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