Project 3 is dedicated to addressing dyslipidemia, a condition characterized by common lipid abnormalities that persist despite conventional treatments, including LDL cholesterol-lowering statins.
Dyslipidemia represents a major risk factor for cardiovascular disease. Even when treatment targets related to blood lipids, blood pressure, and glucose control in diabetes are achieved, not all cases of cardiovascular disease are prevented today.
The target patient population comprises individuals at a high risk of cardiovascular disease and those who do not achieve their treatment objectives with standard therapies. Furthermore, elevated serum triglycerides (SHTG, as described in P1) represent a potential and crucial indication for P3.
For approximately three decades, statins have been the gold standard for treating dyslipidemia. Lipitor, in particular, held the title of the world's best-selling drug for an extended period, reaching a peak annual sales figure of nearly 13 billion USD in 2006. Drawing from this success and similar medications, Lipigon's assessment indicates that this drug possessses blockbuster potential, with the potential to generate annual sales exceeding at least 1 billion USD.
Mechanism of Action
Lipoprotein lipase, known as LPL, represents a highly validated target protein for lipid-related diseases, which encompass conditions stemming from disruptions in the body's fat metabolism. LPL is an enzyme that plays a pivotal role in breaking down fats within the bloodstream. By enhancing LPL activity, it leads to a reduction in triglyceride levels and an elevation in "good" HDL cholesterol levels. This, in turn, mitigates the risk of cardiovascular diseases and type 2 diabetes.
Lipigon collaborates with the esteemed DEL (DNA-encoded library) screening firm, HitGen, to identify small molecules that activate LPL and possess the potential to serve as promising drug candidates.
DNA-encoded chemical libraries (DEL technology) is a highly efficient technique that allows the screening of thousands of times more compounds than traditional screening technologies – up to hundreds of billions of compounds. This technology has demonstrated remarkable efficacy in the pursuit of small molecules that can effectively target complex protein targets.
The key advantage of small molecules is their suitability for oral administration in tablet form. For indications involving millions of patients requiring lifelong treatment to mitigate the risk of cardiovascular disease, tablets offer the most practical and preferred method of delivery.
As of now, there are no available drugs comprised of selective LPL-binding small molecules to address high blood lipid levels, and there is no ongoing development of such medications either.
Lipigon engaged in a two-year collaboration with AstraZeneca to develop an efficient testing system designed to sift out undesirable compounds during the screening process for substances that activate lipoprotein lipase (LPL). This successful endeavour paved the way for Lipigon to establish a strategic partnership with the esteemed DEL (DNA-encoded library) screening firm, HitGen, in 2020, marking the beginning of their joint DEL screening initiatives.
HitGen boasts collaborative ties with several of the world's leading pharmaceutical giants, including Merck, Pfizer, Johnson & Johnson, and Sanofi.
The partnership arrangement with HitGen entails both organizations working hand in hand to identify and develop potential drug candidates. Lipigon assumes responsibility for subsequent preclinical and clinical development efforts, as well as the outlicensing of drug candidates, with HitGen participating in a share of Lipigon's future revenue streams for each project.
Project Status Update
In 2022, Lipigon and HitGen successfully pinpointed small molecules that activate LPL, offering promising starting points for the development of new drug candidates targeting lipid disorders and cardiovascular diseases.
The next phase involves Lipigon utilizing its internally developed validation platform, which was established in collaboration with AstraZeneca, to evaluate the effectiveness of these discovered small molecules. In instances where Lipigon decides to advance with a specific compound, the company will secure licensing rights from HitGen for the development and commercialization of these compounds.
Moreover, Lipigon has broadened its collaboration with HitGen to encompass an additional target protein within a related therapeutic area, while also extending the existing agreement.