News

• Primary endpoint of slowed coronary plaque progression reported to have been met with VASCEPA
• Significant coronary plaque regression of low attenuation plaque (LAP) reported with VASCEPA provides further insight to potential mechanisms of action
• VASCEPA is the first and only agent studied on top of statins reported to exhibit coronary plaque regression in hypertriglyceridemic patients

TORONTO, Aug. 31, 2020 /CNW/ - HLS Therapeutics Inc. ("HLS" or the "Company") (TSX: HLS), a specialty pharmaceutical company focusing on central nervous system and cardiovascular markets, announced today that the trial results from Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients with Elevated Triglycerides on Statin Therapy: Final results of the EVAPORATE Trial were presented at ESC Congress 2020, the annual meeting of the European Society of Cardiology, on August 29, 2020, by Matthew Budoff, M.D., Director of Cardiovascular CT at The Lundquist Institute and Professor of Medicine at the David Geffen School of Medicine at UCLA, the study sponsor. VASCEPA® (icosapent ethyl) demonstrated significant, 17% regression of low attenuation plaque (LAP) volume on multidetector computed tomography (MDCT) compared with placebo over 18 months. As referenced below, these final results can be found in the concurrent publication in European Heart Journal.

"EVAPORATE provides important mechanistic data on coronary plaque characteristics that are potentially relevant to the overall REDUCE-IT® results and clinical use of icosapent ethyl," commented Matthew Budoff, M.D., Director of Cardiovascular CT at The Lundquist Institute and Professor of Medicine at the David Geffen School of Medicine at UCLA. "The REDUCE-IT REVASC analysis presented at American Society of Preventive Cardiology last month reported an early coronary revascularization benefit signal with sustained statistical significance attained by 11 months. EVAPORATE is the first demonstration of imaging results with icosapent ethyl using MDCT. The coronary plaque reduction shown in EVAPORATE is consistent with the benefits of icosapent ethyl in cardiovascular event outcomes shown in REDUCE-IT, a separate study."

A total of 80 patients were enrolled in the randomized, double-blind, placebo-controlled EVAPORATE trial. Patients had to have coronary atherosclerosis as documented by MDCT (1 or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels (mean TG at baseline was 259.1 mg/dL [+/- 78.1] , (2.93 mmol/L [+/-0.88]). Patients underwent an interim scan at 9 months and a final scan at 18 months. The prespecified primary endpoint was a comparison of change in LAP volume at 18 months between icosapent ethyl and placebo. EVAPORATE was not powered for long-term outcomes.

The final results showed a significant reduction in the primary endpoint; icosapent ethyl reduced LAP plaque volume by 17% from baseline to the 18-month scan, whereas there was a progression of LAP plaque volume in the placebo group. There were significant differences between icosapent ethyl and placebo at study end for secondary endpoints of other types of plaque volume changes, including sequentially total, total non-calcified, fibrofatty, and fibrous plaque volumes. All regressed in the icosapent ethyl group and progressed in the placebo group, (p<0.01 for all). The only secondary endpoint which did not achieve a significant difference between groups in multivariable modeling was dense calcium (p=0.053).

"Coronary plaque regression is an important finding with VASCEPA and may explain, in part, the substantial cardiovascular benefit seen in REDUCE-IT," said Dr Jason Gross, HLS Vice President of Scientific Affairs. "The EVAPORATE study results potentially shed further light on how VASCEPA works to lower residual cardiovascular risk."

The mineral oil placebo, used for consistency with REDUCE-IT, was also analyzed against plaque changes from baseline in another placebo in a separate study. Rates of plaque changes in patients randomized to mineral oil (the placebo cohort) in the EVAPORATE study were compared with rates of plaque changes in the placebo arm of a second study that used a cellulose-based placebo. There was no difference in plaque progression between mineral oil and cellulose based placebos.¹

Limitations of this single study include a small sample size. More study is needed to demonstrate the effects of VASCEPA on coronary plaque to determine the relationship of such effects, if any, on cardiovascular risk reduction.

The publication can be accessed via the following hyperlink to European Heart Journal.

Financial Disclosure
Funding from Amarin Corporation was provided to the sponsor of the EVAPORATE study, The Lundquist Institute, for Dr. Matthew Budoff's work on the study.

ABOUT CARDIOVASCULAR DISEASE
Worldwide, cardiovascular disease (CVD) remains the #1 cause of mortality of men and women.

Multiple primary and secondary prevention trials have shown a significant reduction of 25% to 35% in the risk of cardiovascular events with statin therapy, leaving significant persistent residual risk despite the achievement of target LDL-C levels.²

Beyond the cardiovascular risk associated with LDL-C, genetic, epidemiologic, clinical and real-world data suggest that patients with elevated triglycerides (TG) (fats in the blood), and TG-rich lipoproteins, are at increased risk for cardiovascular disease.^{3, 4, 5, 6}

ABOUT VASCEPA (ICOSAPENT ETHYL) CAPSULES
VASCEPA (icosapent ethyl) capsules are the first-and-only prescription treatment comprised solely of the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. Vascepa was approved by Health Canada, was 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 Corporation (NASDAQ:AMRN).

ABOUT HLS THERAPEUTICS INC.
Formed in 2015, HLS is a specialty 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 track record of success in these therapeutic areas and at managing products in each of these lifecycle stages. For more information visit: www.hlstherapeutics.com

REFERENCES

1. Lakshmanan S, Shekar C, Kinninger A, et al. Comparison of mineral oil and non-mineral oil placebo on coronary plaque progression by coronary computed tomography angiography. Cardiovasc Res. 2020;116(3):479-482.
2. Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.
3. Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
4. Toth PP, Granowitz C, Hull M, et al. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: A real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.
5. Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.
6. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384:626–635.

FORWARD LOOKING INFORMATION
This release includes forward-looking statements regarding HLS and its business. Such statements are based on the current expectations and views of future events of HLS's management. In some cases the forward-looking statements can be identified by words or phrases such as "may", "will", "expect", "plan", "anticipate", "intend", "potential", "estimate", "believe" or the negative of these terms, or other similar expressions intended to identify forward-looking statements, including, among others, statements with respect to HLS's pursuit of additional product and pipeline opportunities in certain therapeutic markets, statements regarding growth opportunities and expectations regarding financial performance. The forward-looking events and circumstances discussed in this release may not occur and could differ materially as a result of known and unknown risk factors and uncertainties affecting HLS, including risks relating to the specialty pharmaceutical industry, risks related to the regulatory approval process, economic factors and many other factors beyond the control of HLS. Forward-looking statements and information by their nature are based on assumptions and involve known and unknown risks, uncertainties and other factors which may cause HLS's actual results, performance or achievements, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statement or information. Accordingly, readers should not place undue reliance on any forward-looking statements or information. A discussion of the material risks and assumptions associated with this release can be found in the Company's Annual Information Form dated March 18, 2020 and Management's Discussion and Analysis dated August 5, 2020, both of which have been filed on SEDAR and can be accessed at www.sedar.com. Accordingly, readers should not place undue reliance on any forward-looking statements or information. Except as required by applicable securities laws, forward-looking statements speak only as of the date on which they are made and HLS undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise.

SOURCE HLS Therapeutics Inc.