Sequana Medical NV announced that the first two patients from the non-randomized cohort of the MOJAVE study were successfully treated with DSR 2.0, including safe and effective maintenance of euvolemia without the need for loop diuretics, considerable benefit in their cardiorenal status and a dramatic improvement in their diuretic response and loop diuretic requirements. Detailed biomarker analysis of the preceeding RED DESERT and SAHARA trial patients indicates DSR mechanism of action as breaking the vicious cycle of cardiorenal syndrome. Positive interim data from non-randomized cohort of MOJAVE study: The first two patients treated in the non-randomized cohort of the MOJAVE study had heart failure with preserved ejection fraction (HFpEF) and severe diuretic resistance at baseline (mean furosemide equivalent dose of respectively 1,280 and 800 mg per day).

At the start of the study treatment period, loop diuretics were withheld, and patients were treated with DSR 2.0 up to daily for four weeks. After the four-week DSR treatment period, both patients maintained euvolemia without the need of loop diuretics and showed improved cardiorenal status. Their diuretic response nearly normalized with a mean increase of 454% in their six-hour urinary sodium excretion versus baseline.

These interim data also show a broad improvement in their kidney function with an improvement in eGFR, as well as blood urea nitrogen post-treatment vs baseline. Since both patients had HFpEF, their NT-proBNPv levels were within normal ranges at baseline and were maintained post-treatment, indicating that their stable cardiovascular status was preserved. To date, no clinically relevant changes in serum sodium levels or progressive hyponatremia were observed and no serious adverse events occurred, indicating that DSR 2.0 was safe and well tolerated in these first two US patients.

Both patients are currently in the follow-up period without any loop diuretics (since commencing DSR therapy, the first patient is 9.5 weeks off loop diuretics and the second patient is 4 weeks off loop diuretics). The third patient in the non-randomized cohort has been enrolled and will have completed DSR treatment and initial follow-up before year end. An independent Data and Safety Monitoring Board (DSMB) meeting to review the data from the three patients in the non-randomized cohort is planned in early first quarter 2024 to approve the start of the randomized cohort, planned for first quarter 2024.

Breaking the vicious cycle of cardiorenal syndrome (CRS): Cardiorenal syndrome is a key clinical challenge in heart failure and results from the combined vicious cycle of dysfunction of the heart and kidney with hypothesised complex and interconnected mechanisms such as aberrations in hemodynamic, neurohormonal, inflammatory, and sodium handling pathways. Despite the complex multidimensional pathophysiology, the resultant clinical profile is thought to manifest as a self-reinforcing negative feedback cycle characterized by decreased glomerular filtration, increased renal sodium avidity, and congestion, despite escalating diuretic doses. No current therapies have been shown to improve patient outcomes in this complex and poorly understood indication.

Reducing congestion is a key element of therapy but loop diuretics exacerbate many of the core mechanisms thought to underly CRS, thus even worsening diuretic resistance and CRS. Through effective control of the volume status for an extended period of time and thereby avoiding the negative consequences of loop diuretics, DSR has the potential to break the negative feedback cycle of this important indication with clear unmet clinical needs. Extensive analysis of validated biomarkers from patients in the RED DESERT and SAHARA studies shows the benefit from DSR therapy on i) volume status, ii) normalized diuretic response and dramatically reduced loop diuretic dosing, iii) improvement in kidney function, iv) neurohormonal status and signalling, as well as v) cardiovascular parameters. As previously disclosed, in these patients there were no congestion-related re-hospitalizations, a one class improvement in their NYHAvi status and a reduction of 75% in their predicated one-year mortality (based on the Seattle Heart Failure model).

Data from the RED DESERT and SAHARA proof-of-concept studies have been submitted for publication in a peer-reviewed journal. The Company will update the market as soon as it is published.