Lipisense
Lipisense® is Lipigon's most developed project. It initially aims to lower the blood lipid triglycerides in patients with significantly elevated levels.
Project Status Update
Preliminary topline data from the ongoing double-blind, placebo-controlled, randomized Phase II clinical trial are expected in H2 2025. The primary objective of the study is to confirm the previously documented safety profile of Lipisense® in patients with moderately to severely elevated blood lipid levels (HTG and SHTG, respectively). The trial will also assess a range of secondary efficacy endpoints using biomarker analyses, with particular focus on triglycerides, remnant cholesterol, and glucose control. A total of 23 patients were enrolled. During the treatment period, patients received four doses of either Lipisense® or placebo - one subcutaneous injection per week over four weeks-followed by a six-month observation period.
In Q2 2025, Lipigon obtained extended analysis data from the recently completed Phase I trial of Lipisense® in China, conducted by its commercial partner Leaderna. These analyses confirmed the safety findings reported at the initial data readout earlier in 2025 and were consistent with results from the company’s prior Phase I clinical study conducted in Sweden.
In May 2022, clinical Phase I studies of Lipisense® commenced, and in July 2023, the comprehensive safety results were announced. Across all treatment groups, a favorable safety and pharmacokinetic profile were observed. Importantly, the data also confirmed target engagement, indicating a reduction in ANGPTL4 levels in the blood with repeated dosing in the multiple ascending dose (MAD) groups.
Lipigon has made significant progress in developing Lipisense®, with the final preclinical studies successfully completed in 2021. These studies have produced compelling data, demonstrating the drug candidate's efficacy and safety in well-established experimental models. These findings have received validation from independent researchers, affirming that Lipisense® is expected to yield the same therapeutic effects in humans
Partnerships
The development of Lipisense® has been carried out in close collaboration with Secarna, leveraging their advanced platform for antisense drug development. While the formal partnership has concluded, Lipigon now exclusively owns the patent portfolio and the valuable data generated during the collaborative efforts. During the project, certain milestone payments will be directed to Secarna.
In June 2023, Lipigon embarked on a significant development and licensing agreement with Leaderna Therapeutics Ltd. This strategic alliance places the responsibility for Lipisense® development and commercialization in the hands of Leaderna for regions encompassing China, Hong Kong, Taiwan, and Macau. Meanwhile, Lipigon retains the remaining development and commercialization rights. Within the context of this agreement, Lipigon stands to receive substantial benefits, including upfront payments of up to 91 million USD, milestone payments, and royalties on sales achieved within Leaderna's territory.
Indication
Elevated triglyceride levels are associated with an increased risk of cardiovascular disease, type 2 diabetes, and fatty liver disease. High levels of triglycerides in the blood can also lead to a life-threatening condition called acute pancreatitis, which is an acute inflammation of the pancreas.
There are several specific medical conditions where patients experience significantly elevated triglycerides, and where Lipisense® may be used.
Initially, Lipigon focuses on severe hypertriglyceridemia (SHTG), aiming to prevent acute pancreatitis. By reducing triglyceride levels, the risk not only of acute pancreatitis but also of cardiovascular disease, type 2 diabetes, and fatty liver disease is mitigated.
Market
Lipisense is estimated to have a sales potential of at least USD 1 billion annually for the prevention of cardiovascular disease in dyslipidemic patients, as well as for the prevention of pancreatitis in patients with markedly elevated triglyceride levels. The patient population is continuously increasing due to the rising prevalence of obesity, diabetes, and metabolic syndrome, and currently amounts to 151 million and 5 million individuals, respectively, across seven key markets comprising the US, Japan, and five European countries.
Mechanism of Action
Lipigon has developed the drug candidate Lipisense® with the objective of lowering triglyceride levels in the bloodstream. Lipisense® acts specifically by inhibiting the production of the disease-causing protein ANGPTL4. By inhibiting ANGPTL4, Lipisense® enhances the activity of the crucial enzyme lipoprotein lipase, or LPL, which is responsible for breaking down triglycerides. The absence of functional LPL or other irregularities in the LPL system leads to increased triglyceride levels within the bloodstream.
Technology
Lipisense® belongs to the class of RNA drugs known as antisense therapies. In this approach, researchers have crafted a specific RNA strand, called antisense, designed to bind to a particular mRNA molecule, thereby preventing the production of a specific protein – in this case, ANGPTL4. Importantly, this action occurs exclusively in the liver, minimizing the risk of potential side effects that might arise from the widespread inactivation of the protein throughout the body.
Antisense therapies have emerged as a groundbreaking method for treating diseases, and they are now firmly established in the field of medicine.
Antisense technology is particularly effective for targeting proteins that cannot be modulated using traditional small organic molecules.
Development
Professor Sander Kersten, was the pioneer in identifying the ANGPTL4 protein. A significant portion of research dedicated to unraveling the functions of this protein took place at Umeå University, under the leadership of one of Lipigon's founders, Professor emeritus Gunilla Olivecrona.
Genetic studies have shed light on the importance of ANGPTL4, showing that individuals with mutations reducing its activity experience lower triglyceride levels in their blood. Notably, they also exhibit elevated levels of HDL-C, (High-density lipoprotein cholesterol), often referred to as "good" cholesterol, and a decreased risk of cardiovascular disease. Furthermore, studies have shown that reduced ANGPTL4 function leads to improved blood glucose control and a lower risk of type 2 diabetes.
While there are various target proteins for lipid-regulating drugs, such as ANGPTL3, research conducted by both Lipigon and independent investigators consistently identifies ANGPTL4 as the most effective target.
One distinctive advantage of Lipisense® is its regulation of blood lipids during fasting, a state associated with the most severe form of SHTG. Lipisense® demonstrates its peak efficacy when patients are in a fasting state.
Expansion to More Areas of Use
There is also the potential to expand the project into areas with significantly larger patient populations, such as cardiovascular disease prevention. Several genetic studies demonstrate a robust connection between the target protein of the Lipisense® project (ANGPTL4) and the risk of cardiovascular disease.
While elevated triglyceride levels pose a risk for cardiovascular disease, it's essential to recognize that triglycerides alone are not the sole culprit. Triglycerides, like all fats, are water-insoluble and
require assistance to be transported in the bloodstream. This assistance is provided by cholesterol bound to apolipoproteins. The primary contributors to an increased risk of cardiovascular disease are the cholesterol contents within triglyceride-rich lipoproteins and specific breakdown products thereof. Lipisense® plays a crucial role in facilitating the breakdown of triglyceride-rich lipoproteins, resulting in a substantial reduction in cholesterol levels. Consequently, this intervention may significantly decrease the risk of cardiovascular disease.
* Sources:
Richardson, T. G. et al. Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation. Plos Biol 20, e3001547 (2022).
Helkkula, P. et al. ANGPTL8 protein-truncating variant associated with lower serum triglycerides and risk of coronary disease. Plos Genet 17, e1009501 (2021).
Gusarova, V. et al. Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes. Nat Commun 9, 2252 (2018).