Lipigon's project 4 focuses on treating and preventing lung damage associated with Community-Acquired Pneumonia (CAP), a condition that is not a lipid-related disease. The drug candidate is an antisense oligonucleotide targeted at the protein ANGPTL4 (ANGPTL4 ASO) in the same way as in the company's Lipisense® project, P1.

Existing and future knowledge, technical platforms, and preclinical data from the Lipisense® project can be utilized in P4, enabling shortened development times and more efficient resource utilization. This not only contributes to a cost-effective research process but also increases the chances of success by applying proven strategies to new therapeutic areas.

Indication

Pneumonia is one of the most common reasons for hospital admission and can lead to complications such as Acute Respiratory Distress Syndrome (ARDS), a life-threatening condition associated with a decrease in lung function. This decrease is a consequence of alveolitis, which causes fluid accumulation in the alveoli of the lungs, thereby making oxygen uptake more difficult. Initially, Lipigon focuses on treating CAP patients who require oxygen supplementation during hospital care. The treatment aims to support the healing process, shorten the duration of oxygen therapy, expedite the hospital discharge process, prevent the progression to ARDS, and reduce mortality.

ARDS is an indication with pronounced high medical needs due to its high mortality rate and the need for extended intensive care. Beyond mechanical ventilator treatment, options for ARDS are limited, making it crucial to prevent the progression from pneumonia to ARDS and to shorten hospital stays and the need for oxygen therapy. ARDS can be caused by several factors, including sepsis and viral infections such as COVID-19, which opens up further potential future indications.

ANGPTL4 ASO may also have the potential for other lung-related treatment indications. Elevated ANGPTL4 levels have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD), where they are associated with impaired lung function and inflammation. Several studies have also shown that increased expression of ANGPTL4 leads to a poorer prognosis for patients with certain types of lung cancer, while downregulation of ANGPTL4 inhibits tumor growth.

Market

In the USA, Europe, and Japan, 4–5 million people are affected by CAP, and approximately 500,000 individuals suffer from ARDS each year. The primary treatment for CAP is antibiotics (for bacterial pneumonia). Among hospitalized CAP patients, the mortality rate is about 8 percent, while for ARDS, it is around 40 percent. Currently, no approved drug treatment exists for ARDS patients. According to the company's analysis, the CAP project represents a market opportunity worth several billion USD.

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Mechanism of Action

Studies have shown that ANGPTL4 levels are elevated in patients with ARDS and that these levels correlate with the severity and mortality of the disease. Like P1, Lipisense®, the target protein in the CAP project is ANGPTL4, and the same type of nucleic acid medicine, which is expected to be effective, is used.

ANGPTL4 is a protein with two functions. It regulates blood lipids (utilized in the Lipisense® project) and affects vascular function. Through the latter, ANGPTL4 is linked to acute lung injuries. Numerous studies have demonstrated that ANGPTL4 can increase leakage in the lungs' blood vessels, contributing to the development of inflammation-driven lung damage. The mechanism of action for this is not yet fully understood, but research is ongoing internally and with partners. Notably, the effect is independent of the underlying cause of the inflammation, allowing for the treatment with ANGPTL4 ASO in patients with pneumonia without identifying the source of infection. Inhibiting this protein has the potential to improve survival.

Technology

Lipigon has the option to choose from several existing substances for the CAP project, where the selection will be based on suitability for inhalation and absorption in lung tissue. All candidates are of the Locked Nucleic Acid (LNA) gapmer type, which has been shown to be particularly well-suited for human medicine, thanks to its durability in the body and ability to suppress target protein synthesis effectively.

Partnerships

Since September 2020, Lipigon has collaborated with researchers from The Academic Respiratory Initiative for Pulmonary Health at Nanyang Technological University in Singapore and the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences in China.

Nanyang Technological University in Singapore has published several studies underscoring the pivotal role of ANGPTL4 in lung injuries. The protein was among the most significantly upregulated genes in, for example, the Spanish flu of 1918 and the swine flu of 2009.

Lipigon's drug project has been tested in established models for both bacterial and virus-induced pneumonia with promising results during this collaboration.

A possibility going forward could be to start a collaboration with a company specializing in the pulmonary field. As an initial step, Lipigon has initiated discussions with companies that provide solutions for the inhalation of drugs.

Project Status Update

The substances that Lipigon's collaborative partner will evaluate come from the Lipisense® project. This gives the project access to substances that have already been confirmed to be safe and tolerable through previous tests. Based on the promising results from the preclinical studies, the next step for the CAP project is to explore the method of administration, mechanisms of action, and potential side effects.

Following these outcomes, the company will evaluate future development avenues. Concurrently, efforts will be made to prepare for the administration of the drug.