Market Overview

Olatec Therapeutics Enrolls its First Patients in a Phase 2 Clinical Trial in COVID-19 with its Selective NLRP3 Inhibitor, Oral Dapansutrile

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  • Dapansutrile seeks to treat and prevent the damaging effects of IL-1-induced inflammation by mitigating the inflammatory cascade that can lead to a fulminant Cytokine Storm
  • The study will assess the clinical efficacy of dapansutrile versus placebo in ambulatory patients presenting with moderate COVID-19 respiratory symptoms and evidence of early Cytokine Release Syndrome

Olatec Therapeutics LLC announced today that patients are being enrolled in a trial described as: "A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Orally Administered Dapansutrile Capsules for the Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome." This trial will evaluate the safety and efficacy of dapansutrile in approximately 80 ambulatory patients from diverse demographics, randomized 1:1 (dapansutrile:placebo) and treated for 14 days. For more information, please follow the link here to clinicaltrials.gov.

"In our COVID-19 trial, we believe dapansutrile is well positioned as a specific, oral NLRP3 inhibitor to selectively target the immune system's intense inflammatory response to the SARS-CoV-2 viral infection," stated Damaris Skouras, Olatec's co-Founder and CEO. "In a previous clinical trial, dapansutrile was observed to suppress IL-1β and downstream cytokines and chemokines of the inflammatory cascade in patients with the acute gout flares. In a second clinical trial in patients with persistent heart failure, the dapansutrile treatment group showed improvement in heart function compared to the placebo group. In our COVID-19 program, the aim for dapansutrile is similar, to inhibit IL-1β, preventing Cytokine Release Syndrome from becoming a Cytokine Storm, which clinically could keep patients from progressing into severe disease stages of inflammation requiring hospitalization."

SARS-CoV-2, the virus responsible for COVID-19 disease, activates the innate immune signaling sensor NLRP3. Activation of NLRP3 initiates Cytokine Release Syndrome (CRS), an intense inflammatory response, that is frequently documented in COVID-19 patients. As CRS progresses to a fulminant Cytokine Storm, respiratory distress syndrome and multiple-organ failure take place, severely compromising clinical outcome of the patient. Interleukin-1 beta (IL‑1β) is the pro-inflammatory cytokine produced by activation of NLRP3 during CRS. Blockade of IL-1 with the neutralizing biologics administered to COVID-19 patients with severe disease has shown improvements in clinical outcome measures in a growing number of investigational trials, supporting the pivotal role of NLRP3 as a target in early stage disease.

Dr. Charles A. Dinarello, Olatec's Chief Scientific Officer, who discovered and was the first to clone IL-1β establishing the field of cytokine biology, specifically cited that published research has revealed a consistent pattern of hyperinflammation in numerous viral outbreaks, such as seasonal influenza, SARS, H1N1 and now COVID-19. Dr. Dinarello stated, "In ex-vivo samples of SARS-CoV-2 patients, we have shown that activation of NLRP3 and associated inflammation takes place early after viral infection. Death and the severity of COVID-19 has been shown to occur after the virus is no longer a threat, rather in these patients, death occurred from the Cytokine Storm as evidenced by consequent multi-organ damage." The infection results in elevated levels of IL-1β that drive downstream cytokines, such as IL-6. Therefore, based on Dr. Dinarello's investigations, Olatec believes that COVID-19 patients should be treated with a selective NLRP3 inhibitor early in the course of the disease, which the Company further believes could decrease the chances of serious, potentially fatal outcomes.

By downregulating NLRP3 activation, dapansutrile could mitigate against the serious inflammatory effects from the SARS-CoV-2 infection, particularly in high-risk COVID-19 patients. High-risk patients (those with high BMI, diabetes, cardiovascular or pulmonary diseases or immunosuppresive conditions) generally have one thing in common: they typically already have IL‑1β-mediated inflammation due to their underlying conditions, which is exacerbated by viral infection. "Dapansutrile presents a potential opportunity to treat the IL-1-induced inflammation from the SARS-CoV-2 infection, and at the same time, downregulate pre-existing elevated levels of IL-1-induced inflammation in these patients due to their preconditions," said Dr. Dinarello.

About Dapansutrile and Olatec's Pipeline of Analogues

Dapansutrile is in Phase 2 clinical development and has been well-tolerated and shown to improve clinical outcomes in patients with acute gout flare (see clinical trial data published in The Lancet Rheumatology) and heart failure (see clinical trial data published in a poster presentation at the European Society of Cardiology). Dapansutrile has also been observed to have antiinflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction (AMI), contact dermatitis, multiple sclerosis, melanoma and breast cancers, spinal cord injury (SCI) and Alzheimer's disease. Results from several of these studies have been published in a number of peer-reviewed scientific and clinical research publications. In addition to dapansutrile, Olatec's platform of proprietary compounds includes approximately 60 analogues (OLT Analogues) being screened as viable drug candidates. An IP portfolio protecting Olatec's compounds consists of over 115 patents granted, covering dapansutrile and OLT Analogues.

About Dapansutrile's NLRP3 Mechanism of Action

Dapansutrile (lab code: OLT1177®) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]-, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL-18. NLRP3 is one of the most characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections, and rare genetic autoimmune syndromes.

About Olatec Therapeutics LLC

Olatec is a privately held, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1. Olatec's drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology, and has been involved in the discovery and development of first-line inflammation treatments in the market today. Olatec is conducting clinical trials in the United States (FDA) and Europe (EMA) and maintains offices in New York and the Netherlands. For more information, please visit http://www.olatec.com.

Disclaimer & Forward-looking Statement

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.

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