globenewswire news

In Cycle-1^REF Phase 2 clinical trial, tovinontrine demonstrated substantial reduction in NT-proBNP, a biomarker for heart failure, in patients with HFrEF on top of guideline-directed medical therapy, with a favorable safety and tolerability profile

Company continues to advance tovinontrine in a pioneering clinical program targeting PDE9 in heart failure

Results from the Cycle Phase 2 clinical trials will be presented in a plenary session at Heart Failure Society of America Annual Scientific Meeting

BURLINGTON, Mass., Oct. 11, 2026 (GLOBE NEWSWIRE) -- Cardurion Pharmaceuticals, Inc. ("Cardurion"), a clinical-stage biotechnology company discovering and developing new therapeutic approaches for the treatment of patients with cardiovascular diseases, today announced the presentation of data from its Phase 2 Cycle clinical program evaluating tovinontrine (CRD-750) as a novel treatment for heart failure. In patients with heart failure with reduced ejection fraction (HFrEF) in the Cycle-1^REF trial, tovinontrine at two of three doses tested achieved reductions in NT-proBNP, a biomarker of heart failure, through 12 weeks of treatment. Patients enrolled in the Phase 2 Cycle clinical program were already receiving robust background guideline-directed medical therapy for heart failure, including high rates of Entresto^® and SGLT2 inhibitor use. At all doses tested, tovinontrine demonstrated a favorable safety profile.

Tovinontrine is an orally administered phosphodiesterase-9 (PDE9) inhibitor that represents a new mechanism to enhance the natriuretic peptide signaling (NPS) pathway specifically in the cardiomyocyte for the treatment of patients with heart failure. Cardurion is the first company to bring a PDE9 inhibitor into clinical development for the treatment of chronic heart failure. Phase 2 results from the Cycle-1^REF and Cycle-2^PEF clinical trials were presented today in a late-breaking plenary session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting, ASM 2026 in Phoenix, Arizona.

“We are pleased to share these important Phase 2 results from our Cycle program, showing that tovinontrine achieved substantial reduction in the primary endpoint, NT-proBNP, in patients with HFrEF, demonstrating clinical proof of concept for PDE9 inhibition in heart failure. With these Phase 2 efficacy results and favorable safety profile, Cardurion plans to continue advancing tovinontrine as a potential first-in-class therapy to augment existing guideline directed therapies. Tovinontrine has now demonstrated the potential to offer additional benefit to patients on top of current therapies for heart failure, which remains a leading cause of mortality,” said Howard Surks, MD, Chief Medical and Scientific Officer of Cardurion.

The Cycle-1^REF Phase 2 clinical trial randomized 529 participants at global sites to one of three doses of tovinontrine or placebo, on a background of guideline-directed medical therapy. Reductions in NT-proBNP from baseline at 12 weeks were greatest at the tovinontrine 2.5 mg BID dose and slightly smaller reductions were seen at the 25 mg BID dose, with decreases in NT-proBNP observed as early as week 2 and sustained through the 12-week treatment period. Reductions in BNP and increases in plasma and urinary cGMP, both supportive of pathway engagement and biological activity, were observed alongside the NT-proBNP effect. No benefit in NT-proBNP levels was observed at the highest dose (50 mg BID) of tovinontrine tested in the clinical trial. Reductions in NT-proBNP were consistent among patients on and off background Entresto^® and other therapies, supporting the use of tovinontrine with existing guideline-directed regimens.

Dr. Surks continued, “Our scientific team has worked closely with our scientific advisors and Cycle investigators to understand the inverse dose-response observed with tovinontrine in heart failure patients, as we pioneer the development of PDE9 inhibition in heart failure. We believe that this inverse dose-response reflects a counter-regulatory neurohormonal feedback mechanism, triggered by the very high levels of intracellular cGMP achieved in the myocardium at maximal PDE9 inhibition. This hypothesis is supported by published studies and further analysis of the Cycle data which showed an effect where plasma cGMP elevations beyond a threshold attenuated beneficial downstream signaling by the natriuretic receptor signaling pathway.”

“I am highly encouraged by the Cycle study results that position tovinontrine as a promising new therapeutic option to treat heart failure. Reductions in NT-proBNP achieved at the two lower doses of tovinontrine in HFrEF patients, and particularly the reductions of NT-proBNP seen with lower levels of cGMP elevations, suggest a compelling path forward in the clinic,” said Dr. James Udelson, Chief of the Division of Cardiology at Tufts Medical Center and Principal Investigator for the Cycle clinical trials. “Furthermore, it is gratifying to be part of a clinical effort with Cardurion that is advancing our understanding of a central mechanism in heart failure, so that we can establish a stronger foundation for developing new therapies for millions of patients.”

In addition, results from the Cycle-2^PEF Phase 2 trial were presented in a late-breaking presentation at HFSA ASM 2026. In the Cycle-2^PEF trial, 277 patients with heart failure with preserved ejection fraction (HFpEF) were randomized to receive tovinontrine 50 mg BID or placebo. Consistent with the absence of an NT-proBNP effect at the highest dose in Cycle-1^REF, no significant change in NT-proBNP was observed in Cycle-2^PEF at this dose. Additional evaluation of tovinontrine at lower doses in the HFpEF population is warranted.

In both the Cycle-1^REF and Cycle-2^PEF clinical trials, tovinontrine demonstrated a favorable safety and tolerability profile.

About PDE9 inhibition
Phosphodiesterase (PDE) 9 is an enzyme whose elevated activity in patients with heart failure reduces the beneficial effects of the natriuretic peptide signaling (NPS) pathway. The NPS pathway plays an important and protective role in cardiac function, and its activation has been shown to confer outcomes benefit for patients with heart failure. PDE9 is significantly upregulated in patients with chronic heart failure, causing disruption in the NPS pathway. Cardurion is the first company to demonstrate clinical proof-of-mechanism for PDE9 inhibition in patients with chronic heart failure with its PDE9 program.

About Chronic Heart Failure
Heart failure is a prevalent and growing condition that is responsible for substantial morbidity and mortality. Approximately 6.7 million adults in the United States suffer from heart failure, and approximately 50 percent of these patients die from the condition within five years of diagnosis. One in five patients with heart failure are hospitalized annually, and approximately 25 percent of these patients are re-admitted within a month of discharge. Approximately half of all patients with chronic heart failure have reduced ejection fraction (HFrEF) and half have preserved ejection fraction (HFpEF), categorized as different diseases based on the pumping ability of the heart. Significant unmet medical needs remain in heart failure, despite the reductions in morbidity and mortality from currently approved treatments for heart failure.

About Cardurion Pharmaceuticals
Cardurion Pharmaceuticals is a clinical-stage biotechnology company discovering and developing new therapeutic approaches to address cardiovascular diseases. Cardurion has extensive expertise in cardiovascular biology, signaling pathways and drug discovery and development, and it translates that expertise into potentially groundbreaking therapeutics with the promise to address the unmet needs of patients. Cardurion’s clinical-stage pipeline consists of product candidates targeting phosphodiesterase-9 (PDE9) and calcium/calmodulin-dependent protein kinase II (CaMKII). Cardurion is the first company to advance product candidates against these novel and important targets into clinical testing for the treatment of cardiovascular disease. Cardurion is headquartered in Burlington, Massachusetts, with discovery sciences and research facilities in Shonan, Japan. For more information, please visit Cardurion’s website at https://cardurion.com and follow us on LinkedIn.

Contacts
Investors:
Charlie Newman
Chief Business & Operating Officer
charlie.newman@cardurion.com

Media:
Kathryn Morris
The Yates Network LLC
kathryn@theyatesnetwork.com
914-204-6412