Executives from Tenax Therapeutics (NASDAQ:TENX) outlined progress on the company’s Phase III development program for levosimendan in pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) during a fireside chat at Guggenheim’s Emerging Outlook Biotech Conference.
Phase III enrollment underway, with data expected later this year
Chief Executive Officer Chris Giordano said the company is beginning what it expects to be a roughly two-year recruitment period for its second Phase III trial, describing it as a global study that was initiated in the fourth quarter of last year. He added that Tenax is nearing the end of enrollment in its first Phase III trial, a U.S.-Canada study targeting 230 randomized subjects. The company has guided to complete enrollment in the first half of this year, with data expected in the second half.
Rationale in PH-HFpEF and how Tenax frames levosimendan’s mechanism
Management discussed why prior pulmonary hypertension drugs have struggled to translate hemodynamic changes into functional improvements in Group II patients. Giordano said many drugs that lower pulmonary vascular resistance (PVR) in pulmonary arterial hypertension have shown improved functional outcomes, such as better performance on the six-minute walk test, but those results have not consistently carried over when similar approaches were tried in Group II pulmonary hypertension, where exercise can drive substantial increases in wedge pressure.
According to Giordano, Tenax is pursuing a “simple target” by using levosimendan’s vasodilatory effects to reduce preload and lower wedge pressure. He noted levosimendan has been approved in other markets for more than 20 years but said it had historically been studied primarily in reduced ejection fraction heart failure, leveraging its calcium sensitization effects on myocardial contractility. In contrast, Tenax argues the PH-HFpEF population is benefiting from a different mechanism.
Giordano pointed to findings from the company’s Phase II experience, saying patients experienced a 29-meter improvement in six-minute walk distance along with clear wedge pressure reductions, without a change in cardiac output. He said that pattern suggests the response is not driven by calcium sensitization in this population, but rather by vasodilation, describing levosimendan as acting “first and foremost” as a potassium ATP channel activator in these patients.
Market size discussion and trial population breadth
Chief Business Officer Doug Randall said the company views PH-HFpEF as a multi-billion dollar commercial opportunity, citing high prevalence and the absence of approved therapies. Randall said Tenax believes there are over 2 million patients in the United States with the condition and “probably a roughly similar amount in Europe.” He said the company expects the largest opportunity to be in the U.S., followed closely by Europe, and also referenced what he described as significant intellectual property for levosimendan in PH-HFpEF.
Asked about varying prevalence estimates, Randall said differences often reflect which patient phenotypes companies target. He said some developers focus on enriching trials for a narrower combined pre- and post-capillary PH (Cpc-PH) HFpEF population, while Tenax’s trials are recruiting across both the Cpc-PH phenotype and isolated post-capillary PH (Ipc-PH), which he said supports the company’s broader estimate of around 2 million U.S. patients.
What Tenax highlighted from Phase II and open-label experience
In discussing the Phase II LEVEL study, management emphasized the use of invasive hemodynamic testing under exercise conditions. Randall said no other PH-HFpEF program has tested invasive hemodynamic effects under exercise, and he cited significant reductions in wedge pressure, central venous pressure, and mean pulmonary arterial pressure in that setting. He also described the observed six-minute walk benefit as a clinical improvement that had not been shown previously in this population.
Giordano also discussed endpoints beyond the six-minute walk test, including:
- KCCQ (Kansas City Cardiomyopathy Questionnaire): Giordano said the FDA values symptom and “feeling” measures in this symptomatic disease, and that an improvement in KCCQ could potentially support an approval, though he said Tenax is not pursuing approval on that basis alone.
- Clinical worsening events: He said clinical worsening is an endpoint prescribers look at, and noted the company’s next trial will run 26 weeks versus 12 weeks, which he said could provide a better chance to show effects on such events.
Giordano and Randall also described patient experience in an open-label extension (OLE) in which patients transitioned from weekly 24-hour home infusions to oral levosimendan after Tenax obtained rights to the oral formulation. Giordano said 18 of 19 eligible patients agreed to undertake an “unplanned intensive phase” requiring visits every two weeks for uptitration from 1 mg to 2 mg to 3 mg. He said nine patients remain on therapy today under named patient INDs set up by their institutions.
Management said open-label oral data showed improvements across KCCQ, BNP lowering of more than 20%, and six-minute walk improvements once patients reached 3 mg. Randall added that pharmacokinetic results “did as well,” with higher blood levels of OR-1896, the active metabolite. He noted that in the oral study patients received 1 mg three times daily, which he contrasted with dosing-cycle dynamics in an infused study where patients could be tested at times when they had “no levosimendan.”
Phase III design, powering, and adherence observations
Tenax said its two Phase III trials share the same inclusion criteria and are intended to enroll similar patients, though Giordano noted global enrollment may yield differences in patient weight profiles. He said the 26-week duration and larger size of the global trial are expected to generate a significant amount of safety data for regulators.
Management also discussed how it sought to enrich for responders based on earlier experience. Randall said the company reviewed the hemodynamic profile of responders in the HELP study and used that information in the LEVEL study, including adding elevated right atrial pressure as an additional entry criterion after observing that responders in HELP had elevated right atrial pressure. He also cited a high percentage of HELP patients—about 85%—who had decreased wedge pressure following a 24-hour infusion.
Giordano reviewed a prespecified blinded sample size reassessment conducted in the Phase III program. He said the tool was included to maintain 90% power in case endpoint variability was higher than expected, given the limited dataset available from HELP. He noted Tenax initially planned a 150-patient Phase III study, later expanding to 230 subjects after financing in mid-2024. Based on the reassessment conducted after having 12 weeks of data on the first 150 randomized patients, Giordano said the variability was lower than feared and that the study is well-powered to detect a 25-meter change at 12 weeks. He added that Tenax does not believe more enrollment time or additional funding is needed to complete the study.
Regarding adherence to oral dosing, management acknowledged that three-times-daily administration can be challenging in typical real-world settings, but Giordano said compliance in the trial has been high, with few instances of patients missing more than 20% of doses between visits. He attributed adherence partly to the severity of symptoms in this patient population and said more than 95% of patients continue to opt into the open-label extension.
About Tenax Therapeutics (NASDAQ:TENX)
Tenax Therapeutics, Inc is a clinical-stage specialty pharmaceutical company developing drug delivery technologies designed to improve pain management in acute care settings. The company’s proprietary platform leverages biodegradable polymer matrices to create sustained-release formulations of local anesthetics, aiming to extend the duration of pain relief while reducing reliance on opioid medications.
Tenax’s lead development programs focus on injectable formulations intended for infiltration and peripheral nerve block applications, with the goal of providing longer-lasting analgesia following surgical and procedural interventions.
