Tenax Announces New Publication Highlighting Novel Levosimendan Mechanism of Action in Pulmonary Hypertension Patients with Heart Failure and Preserved Ejection Fraction (PH-HFpEF)

• Levosimendan was shown to Reduce Stressed Blood Volume (SBV), a Novel and Highly Relevant Mechanism of Action for PH-HFpEF Patients
• Stressed Blood Volume Reductions Accompany Previously Reported Improvements in Important Cardiovascular Hemodynamic Measurements
• Reduction in Stressed Blood Volume Suggests the Effects of Levosimendan are Modulated Through K-ATP Channel Activation and Resulting Venodilation

MORRISVILLE, N.C.--(BUSINESS WIRE)--Tenax Therapeutics, Inc. (Nasdaq: TENX), a specialty pharmaceutical company focused on identifying and developing therapeutics that address cardiopulmonary diseases with a high unmet medical need, today announced a new publication that identifies a novel mechanism of action behind the improved cardiovascular hemodynamics and exercise tolerance that was reported in the recent Phase 2 HELP Study (Burkhoff et al., JACC Heart Failure 2021; 9:360-70). The HELP Study evaluated levosimendan in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). The new publication, “Changes in Stressed Blood Volume with Levosimendan in Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction: Insights Regarding Mechanism of Action” appears in the Journal of Cardiac Failure. The article is available online as an “Article In Press”. https://www.onlinejcf.com/article/S1071-9164(21)00215-3/fulltext

The authors conducted an in-depth analysis of data from the HELP Study to elucidate the underlying mechanism behind the improved hemodynamic and exercise capacity effects seen in levosimendan-treated patients. Their analysis found that the reductions in pulmonary wedge pressure (PCWP) and central venous pressure (CVP) were independent of any inotropic effect of the drug. Instead, the authors conclude that the reduction in PCWP and CVP shown in the HELP Study was attributable to levosimendan’s ability to lower stressed blood volume (SBV) through its effect on K+ATP channel activation. The splanchnic circulation is composed of the blood that supplies all of the abdominal viscera, and serves as a reservoir to increase or decrease venous return (referred to as stressed blood volume) to the heart as dictated by physiologic conditions. It has been validated that dilating the splanchnic circulation will lower SBV and hence CVP and PCWP in PH-HFpEF (Fudim et al., JACC Heart Failure 2021; 9:293-300). As a result, patients have less shortness of breath and improved exercise tolerance.

“Recently, it has been shown that the splanchnic, or abdominal, circulation is responsible for maintaining normal venous pressure in the systemic and pulmonary vasculature via stressed blood volume levels,” said Stuart Rich, MD, Chief Medical Officer at Tenax Therapeutics stated. “This is an old concept with new relevance, as elevated venous pressures underlie the systemic and pulmonary vascular congestion in PH-HFpEF. Levosimendan is now the first drug ever to demonstrate dilatation of the splanchnic blood vessels which effectively lowers the CVP and PCWP, at rest and during exercise. As a result, it now is the only medication shown to improve exercise capacity in PH-HFpEF as well.”

Chris Giordano, CEO of Tenax Therapeutics, stated, “This publication shares new, and very important mechanistic knowledge about the effects of levosimendan in PH-HFpEF patients. Levosimendan has been acknowledged for years to be a pleiotropic drug with vasodilatory properties. This explanation of its impact on splanchnic venous capacity, in the light of the HELP primary analysis that showed levosimendan improves significantly patients’ 6-minute walk distance, provides further evidence that levosimendan is a novel therapy with the potential to provide important benefits to PH-HFpEF patients. There are currently no approved therapies for these patients.”

Doctor Daniel Burkhoff, Director of Heart Failure, Hemodynamics and Mechanical Circulatory Support Research at the Cardiovascular Research Foundation in New York City, will lead a KOL discussion on Monday, August 16^th, at 10:00 am eastern, to review this mechanism of action and the potential levosimendan has shown to help patients with PH-HFpEF. Audience members must register in advance for the webcast.

Tenax Therapeutics expects to commence a Phase III study of levosimendan in this population in the first half of 2022.

About Tenax Therapeutics

Tenax Therapeutics, Inc., is a specialty pharmaceutical company focused on identifying, developing, and commercializing products that address cardiovascular and pulmonary diseases with high unmet medical need. The Company has a world-class scientific advisory team including recognized global experts in pulmonary hypertension. The Company owns North American rights to develop and commercialize levosimendan and has recently released detailed results from the Phase 2 HELP Study of levosimendan in Pulmonary Hypertension associated with Heart Failure and preserved Ejection Fraction (PH-HFpEF) at the Heart Failure Society of America (HFSA) Virtual Annual Scientific Meeting. Tenax is also developing a delayed release oral formulation of imatinib, designed to avoid the gastric irritation, into a single pivotal trial pursuant to the 505(b)(2) pathway. For more information, visit www.tenaxthera.com.

About Levosimendan

Levosimendan is a pleiotropic drug that works through a unique triple mechanism of action. It initially was developed as an inotrope for intravenous use in hospitalized patients with acutely decompensated heart failure. It was discovered and developed by Orion Pharma, Orion Corporation of Espoo Finland, and is currently approved in over 60 countries for this indication and not available in the United States. Recently it has been shown to be an effective potassium channel activator which targets mechanisms that underlie pulmonary vascular disease and HFpEF. Tenax Therapeutics acquired North American rights to develop and commercialize levosimendan from Phyxius Pharma, Inc.

About Imatinib

Imatinib is an antiproliferative agent developed to target the BCR-ABL tyrosine kinase in patients with chronic myeloid leukemia. The inhibitory effects of imatinib on PDGF receptors and c-KIT suggested that it may be efficacious in Pulmonary Arterial Hypertension. Imatinib reversed the pulmonary vascular disease in animal models of pulmonary hypertension by blocking the PDGF pathway, which has also been shown to be activated in the human disease. In a phase 3 clinical trial imatinib produced significant improvements in exercise capacity and hemodynamics, but a high rate of dropouts attributed largely to gastric intolerance prevented regulatory approval.

Caution Regarding Forward-Looking Statements

This news release contains certain forward-looking statements by the Company that involve risks and uncertainties and reflect the Company’s judgment as of the date of this release. The forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to matters beyond the Company’s control that could lead to delays in the clinical study, new product introductions and customer acceptance of these new products; matters beyond the Company’s control that could impact the Company’s continued compliance with Nasdaq listing requirements; the impact of management changes on the Company’s business and unanticipated charges, costs and expenditures not currently contemplated that may occur as a result of management changes; and other risks and uncertainties as described in the Company’s filings with the Securities and Exchange Commission, including in its annual report on Form 10-K filed on March 31, 2021 and its quarterly report of Form 10-Q filed on May 17, 2021, as well as its other filings with the SEC. The Company disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. Statements in this press release regarding management’s future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

Investor Contact:
John Mullaly
Managing Director
LifeSci Advisors, LLC
C: 617-429-3548
jmullaly@lifesciadvisors.com