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Cardurion Pharmaceuticals Presents Phase 2 Results for Tovinontrine (CRD-750), a PDE9 Inhibitor, as a Novel Treatment for Heart FailureIn Cycle-1REF 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-1REF 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-1REF and Cycle-2PEF 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-1REF 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 actiity, 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-2PEF Phase 2 trial were presented in a late-breaking presentation at HFSA ASM 2026. In the Cycle-2PEF 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-1REF, no significant change in NT-proBNP was observed in Cycle-2PEF at this dose. Additional evaluation of tovinontrine at lower doses in the HFpEF population is warranted. In both the Cycle-1REF and Cycle-2PEF clinical trials, tovinontrine demonstrated a favorable safety and tolerability profile. About PDE9 inhibition About Chronic Heart Failure About Cardurion Pharmaceuticals Contacts Media: 
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