Mr. Craig Millian reports

NEW REDUCE-IT(TM) ANALYSES SHOW VASCEPA(TM) (ICOSAPENT ETHYL) BENEFIT IN HIGH-RISK CARDIOVASCULAR DISEASE PATIENT SUBGROUPS

HLS Therapeutics Inc. today highlighted two data presentations at the 73rd Annual Scientific Sessions of the American College of Cardiology (ACC.24) describing the effects of Vascepa (icosapent ethyl) on reducing major adverse cardiovascular events (MACE) in patients with baseline high or low lipoprotein(a) [Lp(a)] levels, as well as reducing the risk of cardiovascular (CV) events in patients irrespective of baseline LDL-C level. The Reduce-It analysis results relating Lp(a) concentrations with CV risk were also published on-line today in the Journal of the American College of Cardiology (JACC).

"These new findings provide additional important evidence about the clinical utility of Vascepa and further demonstrate its value in reducing cardiovascular events in at-risk patients in key subgroups," said Craig Millian, chief executive officer of HLS. "Our partner Amarin Corp. continues to generate exciting new research and insights from the Reduce-It trial, which build on the already vast body of evidence supporting the clinical benefits of Vascepa."

The subgroup analyses and their key findings are outlined below:

Icosapent ethyl reduces MACE in patients with elevated triglycerides and high or low lipoprotein(a) concentrations: A Reduce-It subanalysis

High Lp(a) concentrations are associated with increased CV event risk, even when LDL-C levels are well managed. There are no treatments currently approved to reduce residual CV risk on top of contemporary medical therapy in patients with high Lp(a) levels.

In this post hoc analysis of Reduce-It, the relationship between continuous baseline Lp(a) concentration and risk of MACE was analyzed in models that also accounted for baseline LDL-C, baseline triglycerides (TG) and double-blind treatment.

Reduce-It participants were randomized to receive either two grams twice daily of icosapent ethyl (IPE) or matching placebo and followed for a median 4.9 years. In this subanalysis, there were 7,026 Reduce-It patients with baseline Lp(a) data and a median Lp(a) value of 11.6 (first quarter to third quarter: 5.0 to 37.4) milligrams/dL. Results showed that baseline Lp(a) had a strong and significant relationship with MACE irrespective of baseline LDL-C, baseline TGs and treatment assignment, and that the benefit of IPE was consistent across Lp(a) concentrations. Importantly, the treatment benefit of IPE was evident across subgroups with both high (less than or equal to 50 milligrams/dL) and low (equals 50 mg/dL and less than 50 mg/dL were HR 0.79 (95 per cent CI 0.64 to 0.97; P equals 0.0248) and HR 0.75 (95 per cent CI 0.66 to 0.84; P equals 50 mg/dL) and less than 50 mg/dL, respectively.

Limitations include that participants in Reduce-It were not selected on the basis of their baseline Lp(a) concentration and that not all Reduce-It patients had available baseline Lp(a) data.

"In this analysis, IPE showed a clear clinical benefit for patients with both high and low Lp(a) levels. IPE provided a relative risk reduction of 21 per cent among patients with an Lp(a) level of less than or equal to 50 mg/dL and 25 per cent for those patients with an Lp(a) level of less than 50 mg/dL," said Dr. Michael Szarek, professor, Division of Cardiology, University of Colorado School of Medicine and a faculty member at CPC Clinical Research. "These findings are important, as high baseline Lp(a) concentrations are a predictor for MACE, and this analysis reinforces IPE's clinical benefit in these at-risk patient subpopulations."

The analysis and its findings were published simultaneously on-line in JACC.

Efficacy of icosapent ethyl for reducing cardiovascular outcomes by baseline low-density lipoprotein cholesterol level

Elevated low-density lipoprotein cholesterol (LDL-C) is a well-established major CV risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. Recent international guidelines recommend lowering LDL-C to less than 55 mg/dL in those patients who are at very high risk for a future CV event.

In this post hoc analysis, investigators explored Reduce-It data to determine if IPE reduces CV outcomes among high-risk CV patients irrespective of baseline LDL-C. Patients were stratified by LDL-C equals 55 mg/dL. The primary outcome was a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or unstable angina.

Among statin-treated Reduce-It patients with baseline LDL-C data, 1,058 (12.9 per cent) had LDL-C equals 55 mg/dL. The primary outcome rate among patients with LDL-C equals 55 mg/dL subgroup, with rates of 17.4 per cent in the IPE group and 21.9 per cent in the placebo group, HR 0.76 (95 per cent CI 0.69 to 0.85; P less than 0.0001). No significant interaction by baseline LDL-C was observed.

Limitations are that randomization was not stratified by baseline LDL-C, however, baseline characteristics were similar among the two baseline LDL-C subgroups. Reduce-It patients were on statin therapy, but with low rates or unavailability of other lipid therapies such as ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or small interfering RNA (siRNA) therapies.

"As we know, LDL-C is a well-established major CV risk factor. These data are important and show that among adults with increased CV risk and elevated TGs, icosapent ethyl clearly reduced the rate of CV outcomes irrespective of baseline LDL-C, including in those with very-well-controlled LDL-C less than 55 mg/dL," said Deepak L. Bhatt, MD, MPH, MBA and director of Mount Sinai Fuster Heart Hospital.

All analyses highlighted above were financed by Amarin. Dr. Bhatt served as the principal investigator for Reduce-It and his institution received research funding from Amarin.

About Reduce-It

Reduce-It was a global cardiovascular outcomes study designed to evaluate the effect of Vascepa in adult patients with LDL-C controlled to between 41 and 100 mg/dL (median baseline 75 mg/dL) by statin therapy and various cardiovascular risk factors including persistent elevated triglycerides between 135 and 499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other cardiovascular risk factor (primary prevention cohort).

Reduce-It, conducted over seven years and completed in 2018, followed 8,179 patients at over 400 clinical sites in 11 countries with the largest number of sites located within the United States. Reduce-It was conducted based on a special protocol assessment agreement with FDA. The design of the Reduce-It study was published in March, 2017, in Clinical Cardiology.

About cardiovascular disease

Worldwide, cardiovascular disease (CVD) remains the No. 1 cause of mortality of men and women.

Controlling bad cholesterol, also known as LDL-C, is one way to reduce a patient's risk for cardiovascular events, such as heart attack, stroke or death. However, even with the achievement of target LDL-C levels, millions of patients still have significant and persistent risk of cardiovascular events, especially those patients with elevated triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25 to 35 per cent.

About Vascepa (icosapent ethyl) capsules

Vascepa capsules are the first-and-only prescription treatment solely comprising the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. Vascepa was approved by Health Canada and added to Health Canada's Register of Innovative Drugs and benefits from data protection for a term of eight years, as well as being the subject of multiple issued and pending patents based on its unique clinical profile. HLS in-licensed the exclusive rights to Vascepa for the Canadian market from Amarin.

About HLS Therapeutics Inc.

Formed in 2015, HLS is a pharmaceutical company focused on the acquisition and commercialization of late-stage development, commercial stage promoted and established branded pharmaceutical products in the North American markets. HLS's focus is on products targeting the central nervous system and cardiovascular therapeutic areas. HLS's management team is composed of seasoned pharmaceutical executives with a strong record of success in these therapeutic areas and at managing products in each of these life cycle stages.

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