57% Cholesterol Reduction from NYX-PCSK9i In Vivo Study
Nyrada Inc. Level 4, 828 Pacific Highway , G ordon NSW 2072 ARBN 625 401 818 57% Reduction in Total Cholesterol from Nyrada’s NYX - PCSK9i In Vivo Study • Very e ncouraging preliminary in vivo efficacy results for Nyrada’s oral PCSK9 inhibitor NYX - PCSK9i , show ing a 57 % reduction in total cholesterol • Provides proof - of - concept in a speciali s ed mouse model which has demonstrated high predictability of human cholesterol metabolism and cardiovascular health outcomes • NYX - PCSK9 i r esults compare favourably with historical in vivo trials of the statin , Lipitor ® (Pfizer) , and injectable PCSK9 monoclonal antibody, Praluent ® (Sanofi/Regeneron) , in the magnitude of total cholesterol reduction • Results mark significant progress towards a n effective, convenient , and cost - competitive single - pill treatment option for the 70% of patients unable to reach their target LDL cholesterol level despite taking a statin , replacing ongoing expensive injections • Results confirm the dose to be carried forward into further testing of NYX - PCSK9i in combination with a statin to determi ne potential cholesterol - lowering enhancement Sydney, 21 December 2020 : Nyrada Inc (ASX: NYR) is pleased to report encouraging efficacy results from its cholesterol - lowering drug program which is directed at develop ing a n oral PCSK9 inhibitor treatment for hypercholesterolemia (high cholesterol) . Preliminary data, from a n in vivo study evaluating Nyrada’s lead product candidate, NYX - PCSK9i , has shown it reduces total cholesterol, including LDL cholesterol , in the A PO E*3 - Leiden.CETP mouse model by 57 %. Two dose levels ( 3 0 and 50 mg/kg ) were administered and evaluated over 28 days , with a dose - dependent response observed (see Figure 1 and Table 1 ) . No adverse effects were identified and NYX - PCSK9i was well - tolerated at both dose level s . Additional exploratory analys e s will continue for secondary study measures , which Nyrada anticipates reporting in the N ew Y ear . Figure 1 . Total Cholesterol Reduction to NYX - PCSK9i in A PO E*3 - Leiden.CETP Mouse Model Nyrada Inc. Level 4, 828 Pacific Highway , G ordon NSW 2072 ARBN 625 401 818 Table 1. Percentage change in total cholesterol when compared to vehicle control. There were 8 mice in each experimental group. P - values are shown in brackets, with significant p - values in bold % difference in plasma total cholesterol versus vehicle control ( p - value) Time (days) 7 14 21 28 30 mg/kg NYX - PCSK9i - 14% (0.05) - 23% (0.015) - 32% (0.002) - 36% (<0.001) 50 mg/kg NYX - PCSK9i - 16% (0.05) - 40% (<0.001) - 50% (<0.001) - 57% (<0.001) Prof. Gilles Lambert, Nyrada Scientific Advisory Board Member and Professor in Cell Biology and Biochemistry at the University of La Réunion Medical School commented: “ The results from this study are extremely promising and build on the results reported in July which d emonstrated equivalency of NYX - PCSK9i to the PCSK9 monoclonal antibod y medications Repatha ® and Praluent ® in protecting low - density lipoprotein receptors (LDLR) from degradation in healthy human white blood cells. The in vivo study demonstrates proof - of - co ncept within whole - system biology and, importantly, in a mouse model known to be highly predictive of human outcomes . ” James Bonnar, Nyrada CEO commented: “These very encouraging results advance the possibility for a n effective, convenient , and cost - competitive oral PCSK9 inhibitor cholesterol - lowering treatment, either as a monotherapy for those who are statin - intolerant or combined with a generic statin in a single pill . This w ould benefit the 70% of patients at risk of cardiovascular dise ase who struggle to reach their target LDL cholesterol level despite taking a statin 1 . Currently, the best option for t hese patients is ongoing adjunct treatment on top of a statin with expensive and inconvenient injectable drugs such as Repatha ® and Praluent ® , or Leqvio® (inclisiran, Novartis) the injectable siRNA inhibitor recently approved in Europe . ” “ The lipid management medicine market is substantial and growing, with statin s Crestor ® and Lipitor ® the number 1 and 2 most prescribed drugs in Aust ralia. Combined global sales of Repatha ® or Praluent ® exceeded US$900 million in FY2019. We look forward to updating the market with further results as we advance the program towards the first human study in late 2021 . ” Comparison with Current Treatments The results from the NYX - PCSK9i in vivo study indicate that, under similar testing conditions, NYX - PCSK9i is comparable with FDA approved cholesterol - lowering drugs from two classes : a statin , Lipitor ® (atorvastatin, Pfizer) , and the monoclonal antibody , Praluent ® ( alirocumab, Sanofi/Regeneron) . Given that NYX - PCSK9i has been shown in this study to be effective and orally bioavailable, it is positioned to provide a substantial advancement over injectable drugs such as monoclonal antibod y PCSK9 inhibitor s Repatha ® ( e volocumab , Amgen) and Praluent ® , which are prohibitively expensive ( A $5, 8 00 – A$8,700 per year) and inconvenient for patients , requiring dosing by injection every two to four weeks for life . 1 Wong ND et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low - density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011 – 2012. J Clin Lipidol . 2016;10(5): 1109 – 1118 Nyrada Inc. Level 4, 828 Pacific Highway , G ordon NSW 2072 ARBN 625 401 818 In 20 13 , a study by Berbée a nd colleagues 2 evaluated the total cholesterol response to a moderate dose of a torvastatin ( Lipitor ® ) in the A PO E*3 - Leiden.CETP mouse model and showed a 22 % reduction in total cholesterol when administered over 18 weeks . In 20 20 , a study by Härdtner and colleagues 3 evaluated the total cholesterol response to a n optimal dose of Lipitor ® in the A PO E*3 - Leiden.CETP mouse model and showed a 5 0 % reduction in cholesterol when administered for 2 0 - week s . Similarly, the NYX - PCSK9i in vivo study results are comparable to a study of alirocumab ( Praluent ® ) , a PCSK9 monoclonal antibody. In the 20 14 study by Kühnast and colleagues 4 , a lirocumab was shown to reduce cholesterol by 37 - 46% (moderate - optimal dose) in A PO E*3 - Leiden.CETP mice when injected weekly for 18 weeks . T he A PO E*3 - Leiden.CETP mouse model has historically been shown to be a highly predictive model of the cholesterol - lowering effect in human clinical studies. The in vivo results announced today follow previously announced encouraging efficacy data from a n earlier study of NYX - PCSK9i in healthy human white blood cells (lymphocytes) ( ASX Announcement 6 July 2020 ) . Th e study found NYX - PCSK9i to be effective in increasing the surface expression of LDL receptors which are necessary to lower cholesterol in patients. NYX - PCSK9i also demonstrated equivalency with the two approved monoclonal PCSK9 antibody d rugs Repatha ® and Praluent ® . Ne x t Steps Nyrada anticipates reporting full study outcomes in Q1 of 2021 once all study parameters have been analy s ed and the final report issued . In the meantime, the C ompany has initiated large r - scale production of NYX - PCSK9i, ahead of preclinical regulator y studies to commence in Q1 2021. Nyrada will continue to evaluate the efficacy of NYX - PCSK9i in reducing cholesterol in a further in vivo stud y utili s ing the same A PO E*3 - Leiden.CETP mouse model . T he study will in vestigate a high dose of NYX - PCSK9i, with and without a statin , to explore the maximal effect as a monotherapy and the potential enhanc e ment effect when dosed in combination. The study is expected to commence in Q1 2021 and take 6 - 8 weeks . Nyrada has filed a provisional composition of matter patent for PCSK9 inhibitor NYX - PCSK9i and related compounds . Nyrada U ses a S peciali s ed T ransgenic M ouse M odel Nyrada selected a speciali s ed mouse model called the A PO E*3 - Leiden.CETP mouse model which has been specifically generated to possess human - like characteristics concerning cholesterol metabolism and cardiovascular health. The model expresses three human genes to specifically model the human hyperlipidaemia condition and is very well regarded in the cardiovascular field, having been used for over 170 drug intervention studies by the pharmaceutical industry over the last 15 years. 2 Berbée JF P et al. Resveratrol protects against atherosclerosis but does not add to the antiatherogenic effect of atorvastatin in APOE*3 - Leiden.CETP mice. J Nutr Biochem. 2013;24(8): 1423 - 1430 3 Härdtner C et al. Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering . Basic Res Cardiol. 20 20 Dec ; 115 : 78 4 Kühnast S et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin . J Lipid Res. 2014 Oct; 55(10) : 2103 – 2112 Nyrada Inc. Level 4, 828 Pacific Highway , G ordon NSW 2072 ARBN 625 401 818 Why is LDL Important to Health and what is the Role of PCSK9? When the body has too much LDL (bad) cholesterol, it can accumulate on artery walls, restricting blood flow which can lead to heart attack and stroke. LDL cholesterol is cleared from circulation by binding to LDL receptors (LDLR) on the surface of liver cells. PCSK9 is a naturally produced protein that plays a counter role in this regulation process. It does this by degrading the LDLR, lowering the number of receptors available to remove LDL cholesterol. This leads to increased levels of LDL cholesterol in the bloodstream. Inhibitio n of PCSK9 function causes a beneficial increase in LDLR on the surface of cells, improving the body’s ability to clear LDL cholesterol from the bloodstream. Glossary In vivo A medical test, experiment, or procedure that is done on (or in) a living organi sm such as a laboratory animal or human. LDL Low - density lipoprotein cholesterol often referred to as “bad” cholesterol. LDLR Low - density lipoprotein receptor. This receptor binds to particles called low - density lipoproteins (LDLs), which are the primary carriers of cholesterol in the blood. NYX - PCSK9i NYX - PCSK9i is the Nyrada oral small molecule PCSK9 inhibitor, developed to bind to PCSK9 with the purpose to increase LDLR levels and thus reduce LDL cholesterol. PCSK9 Proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme predominantly produced in the live r. PCSK9 is a key player in plasma cholesterol metabolism. Statistical significance Statistical significance is a measure of how likely a test result is likely to be due to chance e. g., a p - value of 0.05 means there is a 5% likelihood that the result is a false positive and a 95% likelihood that it is real. A p - value of 0.001 means there is a 0 .1% likelihood that the result is a false positive and a 99.9% likelihood that the result is real. In general, the larger the study size, or the larger the effect, the lower the p - value. General Nyrada has a solid cash position having A $ 5 . 2 million in the bank on 3 0 September 2020. Also , the Company is actively pursuing a variety of non - dilutive funding and collaboration opportunities for the development of its drug candidates. The Company also confirms that its operations and supply chains currently remain unaffected by the COVID - 19 pan demic . About Nyrada Inc Nyrada is a preclinical stage, drug discovery , and development company, speciali s ing in novel small molecule drugs to treat cardiovascular and neurological diseases. The Company has two main programs, each targeting market sectors of significant size and considerable unmet clinical need. These are a cholesterol - lowering drug and a drug to treat brain injury, specifically traumatic brain injury and stroke. Nyrada Inc. ARBN 625 401 818 is a company incorporated in the state of Delaware US, and the liability of its stockholders is limited. - ENDS - Authori s ed by Mr . John Moore, Non - Executive Chairman, on behalf of the Board Nyrada Inc. Level 4, 828 Pacific Highway , G ordon NSW 2072 ARBN 625 401 818 Investor & Corporate Enquiries: Company Secretary: Prue Kelly David Franks T: 0459 022 445 T: 02 8072 1400 E: email@example.com E : David.Franks@automicgroup.com.au Media Enquiries: Catherine Strong Citadel - MAGNUS T: 02 8234 0111 E: firstname.lastname@example.org Website : www.nyrada.com Forward - l ooking Statements This announcement may contain forward - looking statements. You can identify these statements by the fact they use words such as “aim”, “anticipate”, “assume”, “believe”, “con tinue”, “could”, “estimate”, “expect”, “intend”, “may”, “plan”, “predict”, “project”, “plan”, “should”, “target”, “will” or “would” or the negative of such terms or other similar expressions. Forward - looking statements are based on estimates, projections , and assumptions made by Nyrada about circumstances and events that have not yet taken place. Although Nyrada believes the forward - looking statements to be reasonable, they are not certain. Forward - looking statements involve known and unknown risks, uncerta inties , and other factors that are in some cases beyond the Company’s control that could cause the actual results, performance , or achievements to differ materially from those expressed or implied by the forward - looking statement.
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