First Patient Enrolled in a Phase 2 Study in Patients with Type 2 Diabetes with Olatec's NLRP3 Inhibitor, Dapansutrile

• The first patient with type 2 diabetes mellitus (T2D) and diabetes-related complications has been enrolled in a clinical trial called DAPAN-DIA in Basel, Switzerland, with Olatec's NLRP3 inhibitor, dapansutrile, which is sponsored by Principal Investigator, Marc Donath MD
  
  
• This Phase 2 randomized study is designed to evaluate dapansutrile's efficacy and safety in approximately 300 patients with elevated blood glucose, systemic inflammation and at risk for complications of diabetes, despite use of standard-of-care anti-diabetic therapy
  
  
• DAPAN-DIA represents the first T2D clinical trial of any selective NLRP3 inhibitor in the emerging class that will also assess cardiometabolic and other risk factors beyond anti-hyperglycemic effects including weight lowering efficacy in combination with GLP-1 therapy
  
  
• The trial is being funded by a consortium that includes Olatec, the European Union under the Horizon Europe Programme (GA No 101095433) and the Swiss Government as part of the INTERCEPT-T2D initiative

NEW YORK, July 11, 2024 /PRNewswire/ -- Olatec Therapeutics, Inc. (Olatec), a leader in the emerging class of specific NLRP3 inhibitors, announced patients with type 2 diabetes mellitus (T2D) and diabetes-related complications (the DAPAN-DIA Study) are being enrolled in a Phase 2 clinical trial in Basel, Switzerland.

The DAPAN-DIA Study is a randomized, double-blind, placebo-controlled multi-center trial of the efficacy and safety of dapansutrile in subjects with T2D and diabetes-related complications. Target enrollment is approximately 300 patients who, upon entry into the trial, present with low-grade inflammation, obesity and inadequately controlled glycemia (elevated HbA1c) despite use of standard anti-diabetic therapy. Patients will be treated with dapansutrile or placebo for six months. "We expect the data from this trial, including the combination with GLP-1 therapy, will be highly relevant for understanding the full potential of anti-inflammatory intervention with an NLRP3 inhibitor in this setting," shared Mustafa Noor MD, Chief Medical Officer, Olatec Therapeutics.

The study is being conducted as an investigator-sponsored study under Principal Investigator Marc Donath MD at the University Hospital of Basel in Switzerland, a long-time Olatec collaborator and advisor as well as a leading researcher-clinician in immuno-metabolism. In addition to the Swiss sites, the trial is intended to be expanded at medical and scientific diabetes centers of excellence within Europe, including: Hôpital Lariboisière, Hôpital Bichat-Claude Bernard and Hôpital Cochin in Paris, France; German Diabetes Center, Düsseldorf, Germany; and University Hospital of Liège in Belgium. Funding is being provided through the INTERCEPT-T2D initiative by the European Union under the Horizon Europe Programme (GA No 101095433), in collaboration with the Swiss Government and Olatec.

T2D is a chronic condition characterized by elevated levels of glucose in blood, resulting from insulin resistance and inadequate insulin secretion.  The disease is often concurrent with obesity and associated with a range of complications, including cardiovascular disease, renal dysfunction, retinopathy, neuropathy, and non-alcoholic steatohepatitis, where chronic, elevated low-grade systemic inflammation and activation of NLRP3 and upregulation IL-1β are observed. Unlike existing diabetic treatments that primarily focus on glucose lowering, dapansutrile offers a novel approach to disease-course modification, by targeting the underlying NLRP3 inflammation pathway that is implicated in driving resistance to insulin action in T2D, promoting body weight gain and associated with higher cardiometabolic risks. 

Dr. Donath stated that, "there is a large unmet need for effective treatment of T2D that goes beyond glycemic control and addresses the underlying inflammatory component of the disease and its cardiometabolic complications. The ground-breaking DAPAN-DIA Study has the potential for dapansutrile to represent a significant step forward in the management of T2D."

Olatec's Founder and CEO, Damaris Skouras, commented: "Building on our previous data in heart failure and gout, DAPAN-DIA Study represents a major milestone in the development of dapansutrile in the inter-related cardiometabolic diseases linked by chronic low-grade inflammation due to NLRP3/IL-1 activation."

About Type 2 Diabetes
Type 2 diabetes (T2D) is a serious, chronic condition that occurs when levels of glucose in blood are elevated because the body cannot produce any or enough of the hormone, insulin, or cannot effectively use the insulin it produces. Insufficient amount of insulin, or the inability of cells to respond to it (insulin resistance), leads to high levels of blood glucose, which is the clinical indicator of T2D and measured clinically as HbA1c.  High blood sugar levels can cause damage to many of the body's organs, leading to disabling and life-threatening health complications.  Life expectancy for typical patients with T2D has been estimated to be 8 years shorter and driven by 200% increased risk of all-cause mortality. Approximately 70% die from atherosclerotic cardiovascular disease, 40% develop chronic kidney disease (CKD) due to diabetic nephropathy, and almost one-third develop retinopathy. As the prevalence of T2D increases globally, the condition and its associated complications are generating considerable - - and growing - -economic burden on healthcare systems and societies. In 2021, USD $966 billion in global health expenditures were due to T2D, which represents 316% increase over the last 15 years. There are an estimated 537 million adults living with diabetes worldwide, with the total number predicted to rise to 643 million by 2030 and 784 million by 2045. (Source: IDF Atlas 2021)

About Scientific Rationale for NLRP3 in Type-2 Diabetes

Low-grade chronic inflammatory response is one mechanism leading to the development of insulin resistance, T2D, and associated comorbidities, including liver and kidney damage. In particular, the NLRP3 inflammasome has been shown to play a central role in orchestrating inflammation and immune responses as it is activated in response to several altered metabolic signals in T2D, leading not only to the activation of caspase-1 and production of IL-1β, but also to insulin resistance and pancreatic β cell failure. Furthermore, activation of the NLRP3 inflammasome has been shown to promote vascular inflammation, endothelial dysfunction, and plaque destabilization, contributing to the pathogenesis of atherosclerosis and cardiovascular events. Antagonism of IL-1 pathways has been shown to prevent β-cell dysfunction and to improve glycaemia, cardiovascular complications and heart failure and it may counteract other complications of diabetes. Therefore, targeting this pathway in patients with T2D may have numerous therapeutic advantages over current treatments. (Reviewed by Donath and Dinarello Nature Reviews 2019).

About Dr. Marc Donath, Principal Investigator 
Prof. Dr. Marc Donath is the Chief Physician, Clinic of Endocrinology, Diabetes & Metabolism, University of Basel. Dr. Donath's research aims at the understanding of the pathogenesis of type 2 diabetes, specifically to identify the inflammatory process underlying failure of insulin production in type 2 diabetes. Dr. Donath's work has contributed to the concept that the innate immune system is an integral component in the regulation of metabolism and shows that modulation of the immune system with anti-inflammatory intervention may improve the overall metabolic health and reduce cardiovascular risk in patients with type 2 diabetes.

About the INTERCEPT-T2D Consortium
INTERCEPT-T2D, which stands for Early Interception of Inflammatory-mediated Type 2 diabetes, coordinated by Nicolas Venteclef U1151 at INSERM (French National Institute of Health and Medical Research) represents a consortium of entities including Olatec, and several established European diabetes centers in addition to the Hôpital Lariboisière, Hôpital Bichat-Claude Bernard and Hôpital Cochin in Paris, France; German Diabetes Center, Düsseldorf, Germany; and University Hospital of Liège in Belgium. Funding is being provided from both (i) European Union under the Horizon Europe Programme (GA 101095433) and (ii) the Swiss Government as part of the Horizon Europe Programme and State Secretariat for Education Research and Innovation, respectively.

About Olatec Therapeutics, Inc.
Olatec is a leading, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases. The lead drug candidate, dapansutrile (lab code: OLT1177^®) is a small molecule, specific NLRP3 inhibitor, currently in Phase 2/3 clinical development has demonstrated to date that it is well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). In the heart failure trial, treatment with dapansutrile in subset of subjects with diabetes led to clinically meaningful reductions in fasting glucose levels relative to placebo. Ongoing clinical trials are evaluating dapansutrile in Gout, Parkinson's and Melanoma. For a complete list of Olatec's original publications on dapansutrile in various preclinical and clinical disease areas, please refer to Olatec's publications page, here. For more information, please visit http://www.olatec.com

Disclaimer & Forward-looking Statement
This press release is not an offer to sell and is not soliciting an offer to buy any equity interests in the Company. The information contained herein is being provided for information purposes only. The Company makes no express or implied representation or warranty as to the completeness of this information. Any forward-looking statements contained in this release are based on assumptions made by Olatec at the time this Press Release was prepared. Any forward-looking statement contained in this Press Release is subject to known and unknown risks, uncertainties and other factors that may be materially different from those contemplated in such forward-looking statements. All information with respect to industry data has been obtained from sources believed to be reliable and current, but the accuracy thereof cannot be guaranteed by the Company. Olatec does not undertake any obligation to update or revise the forward-looking statements contained in this Press Release to reflect events or circumstances occurring after the date this Press Release was prepared, or to reflect the occurrence of unanticipated events.

SOURCE Olatec Therapeutics, Inc.