PCSK9

Dyslipidemia, a condition involving unhealthy levels of cholesterols and other fats in the blood, is a major risk factor in cardiovascular diseases, which make up the world’s biggest killer with 17.9 million deaths ​ per year. While there are treatments for dyslipidemia, they are not sufficient to control the blood levels of low-density lipoprotein cholesterol, or ‘bad cholesterol,’ in many patients. The oral drug developed by CSPC is designed to prevent the production of a low-density lipoprotein called lipoprotein (a), which is involved in the transport of cholesterol in the bloodstream. By doing this, it may treat and prevent a range of cardiovascular diseases as a monotherapy or in combination with another small molecule candidate by AstraZeneca’s that depletes low-density lipoproteins by blocking an enzyme called PCSK9. According to the deal terms, CSPC is eligible for $100 million upfront in addition to up to $1.92 billion in payments based on development and commercialization milestones, plus tiered royalties. Sharon Barr, AstraZeneca’s executive vice president and head of biopharmaceuticals R&D stated ​ that the asset “could help patients to more effectively manage their dyslipidemia and related cardiometabolic diseases. Given the scale of unmet need, with cardiovascular disease being a leading cause of death globally, advancing novel therapies that can be used alone or in combination to effectively address known risk factors and advance patient care is particularly important and a key part of our strategy.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); The global market for cardiovascular disease treatments was worth a massive $144 billion in 2023 ​ and is projected to grow by 4% per year to $208 billion by 2030. The market growth is being fuelled by increasingly sedentary lifestyles across the population, leading to higher prevalences of cardiovascular diseases in both young and old people. This is the latest deal showcasing major interest from big pharma companies in cardiovascular disease treatments. AstraZeneca kicked off 2023 with a $1.8 billion takeover of the U.S. drug developer CinCor. Other examples include Novo Nordisk’s takeover of the German player Cardior Pharmaceuticals for up to €1 billion ($1.1 billion) in March this year and Bayer acquiring the European marketing rights to a small molecule cardiovascular disease treatment from Eidos Therapeutics of the U.S. for up to $310 million upfront in the same month. AstraZeneca also has major interest in the field of obesity, having inked another $2 billion licensing deal with China’s Eccogene last year for global rights to the latter’s oral once-daily glucagon-like peptide 1 receptor agonist.

LONDON, UK I October 07, 2024 I AstraZeneca has entered into an exclusive license agreement with CSPC Pharmaceutical Group Ltd (CSPC) to advance the development of an early stage, novel small molecule Lipoprotein (a) (Lp(a)) disruptor that has the potential to offer additional benefits for patients with dyslipidaemia. This asset further strengthens the company’s cardiovascular portfolio to help address the major risk factors driving chronic cardiovascular disease. Under the terms of the agreement, AstraZeneca will receive access to CSPC’s pre-clinical candidate small molecule, YS2302018, an oral Lp(a) disruptor, with the aim of developing this as a novel lipid-lowering therapy with potential in a range of cardiovascular disease indications alone or in combination, including with the oral small molecule PCSK9 inhibitor, AZD0780. YS2302018 was discovered by CSPC and has been shown to effectively prevent the formation of Lp(a). Lp(a) is a form of low-density lipoprotein (LDL) that plays a key role in the transport of cholesterol in the blood stream. 1 Elevated levels of Lp(a), as well as elevated LDL-cholesterol, are known risk factors for cardiovascular disease, including coronary artery disease and stroke. 2 Sharon Barr, Executive Vice President and Head of BioPharmceuticals R&D, AstraZeneca, said: “This asset is an important addition to our cardiovascular pipeline and could help patients to more effectively manage their dyslipidaemia and related cardiometabolic diseases. Given the scale of unmet need, with cardiovascular disease being a leading cause of death globally, advancing novel therapies that can be used alone or in combination to effectively address known risk factors and advance patient care is particularly important and a key part of our strategy.” Dongchen Cai, Chairman of the Board, CSPC Pharmaceutical Group Ltd, said “Lipoprotein (a) represents a very important target for dyslipidemia and implicated in multiple cardiometabolic diseases. Through this agreement with AstraZeneca and their global capabilities in clinical development and commercialisation, we look forward to accelerating the development of YS2302018, a novel small molecule Lp(a) disruptor to benefit the millions of patients worldwide living with these diseases.” Financial considerations CSPC will receive an upfront payment of $100 million from AstraZeneca. CSPC is also eligible to receive up to $1.92 billion for further development and commercialisation milestones plus tiered royalties. Notes About dyslipidaemia and cardiovascular disease Elevated Lp(a) and LDL-c  levels in plasma are a key risk factor for cardiovascular disease and this is estimated to cause 2.6 million deaths worldwide annually. 2,3 Despite current treatment options, the global burden of dyslipidaemia is on the rise. 4 More than 70% of patients with atherosclerotic cardiovascular disease (ASCVD) are still not achieving their LDL-C target, so there remains a vast unmet need among high-risk patients for more varied and effective treatment options. 5,6 AstraZeneca is investing in a pipeline of medicines for addressing risk factors and slowing progression to chronic cardiovascular disease, including AZD0780, an oral small molecule PCSK9 inhibitor under investigation for the treatment of dyslipidaemia. 7 AstraZeneca in CVRM Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca References 1. Saeedi R, Frohlich J. Lipoprotein (a), an independent cardiovascular risk marker. Clin Diabetes Endocrinol . 2016;2:7. Published 2016 Mar 31. doi:10.1186/s40842-016-0024-x. 2. Vinci P, Di Girolamo FG, Panizon E, et al. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. Int J Environ Res Public Health . 2023;20(18):6721. Published 2023 Sep 6. doi:10.3390/ijerph20186721. 3. World Health Organization (WHO) [Internet]. Raised cholesterol; [cited 2024 October 02. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3236 . 4. Pirillo A, et al. Global epidemiology of dyslipidaemias. Nat Rev Cardiol . 2021;18(10):689-700. 5. Cannon CP, et al. Use of Lipid-Lowering Therapies Over 2 Years in GOULD, a Registry of Patients With Atherosclerotic Cardiovascular Disease in the US. JAMA Cardiol. 2021;6(9):1-9. 6. Krahenbuhl S, et al. Unmet Needs in LDL-C Lowering: When Statins Won’t Do! Drugs . 2016;76(12):1175-90. 7. Vega RB, et al. AZD0780, the first oral small molecule PCSK9 inhibitor for the treatment of  hypercholesterolemia: Results from a randomized, single-blind, placebo-controlled phase 1 trial European Atherosclerosis Society Congress; May 26-29; Lyon, France 2024. SOURCE: AstraZeneca

AstraZeneca is strengthening its cardiovascular disease pipeline with a $100 million upfront deal for a lipid-targeting drug from China’s CSPC Pharmaceutical Group. The UK drugmaker will get the rights to a small molecule lipoprotein(a) disruptor that’s in preclinical development. The candidate, YS2302018, can stop the formation of a lipid that plays a key role in transporting cholesterol in the bloodstream. CSPC could get up to $1.92 billion in milestones as well as tiered royalties on sales, according to an AstraZeneca press release . The company said the drug can be combined with others in its pipeline, including the small molecule PCSK9 inhibitor AZD0780. That candidate is currently in Phase 2 for dyslipidemia, which refers to a basket of diseases characterized by abnormal levels of lipids. Cardiovascular, renal and metabolic disease has been an important area of growth for AstraZeneca in recent years, with the drugmaker investing in external innovation. In November, the company put down $185 million upfront to license an oral GLP-1 agonist from China’s Eccogene. At the start of 2023, it acquired CinCor Pharma and its hypertension drug candidate, baxdrostat, for $1.8 billion . The drugmaker has also been looking more to China for assets, running counter to what some US peer companies have done. At an investor day event in May, CEO Pascal Soriot said innovation has “exploded” in the country and reiterated AstraZeneca’s commitment to tapping said innovation. His comments came in spite of heightened tensions between the US and China, which came to a head last month with the passing of the Biosecure Act. During the company’s most recent earnings call, Soriot said AstraZeneca aims to treat cardiovascular diseases “holistically,” instead of just focusing on weight loss. The company has said combination approaches will be a key part of that strategy. Other noteworthy players working on next-generation cholesterol treatments include Verve Therapeutics, which is advancing a base editing therapy for heterozygous familial hypercholesterolemia. Eli Lilly, meanwhile, has a small molecule lp(a) formation inhibitor, muvalaplin, in Phase 2 development. Novartis is also developing a Phase 3 lp(a) targeting antisense therapy that it licensed from Ionis Pharmaceuticals called pelacarsen.