4TEEN4 Pharmaceuticals GmbH  announced that the first patient has been dosed in a Phase 1b/2a PROCARD1 clinical trial evaluating its monoclonal antibody, procizumab, in patients with shock caused primarily by cardiogenic events. Shock is a life-threatening condition characterized by a sudden breakdown in circulatory function due to end-stage disease or acute events, which often leads to organ failure. With only symptomatic treatment options available, shock is associated with a high mortality rate of over 50%. The Phase 1b/2a trial is designed to identify a target dose for procizumab in preparation for further clinical development. In addition, the trial will provide signals of efficacy. In a Phase 1 study in healthy volunteers, procizumab was well tolerated.

Procizumab is a monoclonal antibody that neutralizes circulating dipeptidyl peptidase 3 (cDPP3), a cardiac depression factor and key pathological driver in shock. Circulating DPP3 degrades angiotensin II, inducing a loss of control over the renin-angiotensin-aldosterone system (RAAS). This dysregulation leads to cardiovascular collapse, marked by organ failure and ultimately, death. In preclinical studies, procizumab has been shown to inhibit cDPP3 activity, resulting in restored control over the RAAS system, normalized cardiovascular function, and improved survival.

“The initiation of this study marks a major milestone for 4TEEN4 as we advance our monoclonal antibody into later-stage clinical trials,” stated Dr. Andreas Bergmann, CEO of 4TEEN4 Pharmaceuticals. “Procizumab has already demonstrated the ability to reverse shock in both pre-clinical models and first clinical use, underscoring its therapeutic potential.”

“Extensive research across more than 100,000 critically ill patients established that high levels of cDPP3 significantly indicate short-term mortality in shock patients,” commented Alexandre Mebazaa, MD, PhD, Professor of Medicine at Université Paris Cité in France and Principal Investigator for the PROCARD1 study. “In many patients, shock progresses rapidly after cDPP3 levels exceed the normal threshold, at which point the likelihood of recovery declines dramatically. Procizumab is designed to intervene by neutralizing the negative effect of cDPP3. This mechanistic approach could enable a significant reduction in mortality by intervening at the biological root of shock, rather than its downstream effects.”

PROCARD1 (NCT06832722) is a multicenter, randomized, double-blind, placebo-controlled Phase 1b/2a trial assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of procizumab in patients with cardiogenic shock and elevated cDPP3 levels. Up to 70 patients will be enrolled across 11 centers in Belgium, the Czech Republic, France, the Netherlands, and Poland. Patients will receive a single intravenous dose of either procizumab at 10 mg/kg, 20 mg/kg, or placebo, alongside standard of care.