ARKAY Therapeutics, LLC, a privately held biopharmaceutical company focused on developing innovative, orally-active combination products for the treatment of type 2 diabetes and related disorders, today announced the submission of an IND application with the U.S. Food and Drug Administration (FDA) to initiate safety, tolerability, and efficacy studies to evaluate the superiority of RK-01, a first-in-class ‘Beta-cell-centric’ combination product, over Metformin in newly diagnosed and obese type 2 diabetes patients with inadequate glycemic control. RK-01 is a proprietary formulation of Valsartan plus Celecoxib dual add-on to Metformin-HCl XR. Metformin is the current first-line of therapy and “gold standard” for the treatment of type 2 diabetes. The component drugs in RK-01 block several complementary inflammatory and hyperglycemic mechanisms that contribute to the progressive deterioration of pancreatic beta-cell function along the immune dysregulation-inflammation-insulin resistance axis. Inflammation-mediated destruction and dysfunction of beta cells compromise their inherent capacity to compensate for insulin resistance and systemic glucose intolerance. Valsartan, an Angiotensin II receptor Type 1 blocker, is currently approved for high blood pressure, and Celecoxib, a selective Cox-2 inhibitor, is currently approved for arthritis; they are being repurposed for the type 2 diabetes space. Activation of Renin-Angiotensin System (RAS) and Cyclooxygenase-2 (Cox-2) in the context of beta cells contribute to the complex pathophysiology of type 2 diabetes. Cox-2-derived pro-inflammatory prostaglandin, PGE2 in pancreatic islets inhibits GLP-1 agonist-mediated glucose-dependent insulin secretion (GDIS) from beta cells. Currently, marketed drugs, such as Victoza, Trulicity, Lyxumia, and Ozempic, are GLP-1 agonists. Novo Nordisk’s blockbuster, Victoza, that led the GLP-1 class of therapy, had sales of US$2.806 billion in 2016. Blockade of inflammation-mediated beta-cell dysfunction is underserved by the modalities used for the currently marketed treatment options.

“This IND submission is an important milestone for the development of ‘Beta-cell-centric’ therapies that maintain a state of insulin sufficiency and reduce the risk of insulin dependence in type 2 diabetes patients,” said Ravi Kumar, Ph.D., founder and CEO of ARKAY Therapeutics.

“On behalf of the company, I would like to thank our scientific advisors and all our collaborators at Albany Medical College, Orange County Research Center, Integrium Clinical Research, and Fisher Clinical Services who helped prepare and submit this IND. We are excited that this novel approach — which represents a new paradigm of treating type 2 diabetes not in isolation, but in the context of comorbidities and coexisting conditions — has the potential to prevent or delay initiation of insulin therapy,” Dr. Kumar added.   

“We’re pleased ARKAY has submitted an IND for a combination product custom-designed to fill clinically the most important gap by targeting multiple pathways that contribute to beta-cell dysfunction, ‘The Core Defect’ in all patients for efficient clinical management of diabetes,” said Dr. Stan Schwartz, MD, a renowned endocrinologist and a medical advisor on ARKAY’s Scientific Advisory Board.

“Each component drug in RK-01 has a unique set of properties to maintain or restore beta-cell function, improve glycemic parameters, and treat coexisting conditions, such as NASH and arthritis. As discussed recently in our publication on Unified Pathophysiologic

Approach to Diabetes and its Complications, RK-01 has the potential to mitigate risks of complications of diabetes in these patients as well,” Dr. Schwartz added. Dr. Schwartz, an emeritus associate clinical professor at University of Pennsylvania, and his colleagues proposed a ‘Beta-cell-centric’ approach for efficient treatment of diabetes by therapeutically targeting cellular defects and mechanisms that contribute to beta-cell dysfunction.

Pending FDA acceptance of the IND, the initial study will test RK-01 for safety and tolerability in healthy adult volunteers, which will be followed by the evaluation of RK-01 for superiority over Metformin monotherapy in newly diagnosed, drug naïve, and obese type 2 diabetes patients with inadequate glycemic control. 

In December 2017, the United States Patent and Trademark Office issued ARKAY’s patent, 9,839,644, that protects the formulations and the method used for RK-01. A continuation patent application, publication number US-2018-0042945-A1, that protects additional formulations and methods has also been filed.