4TEEN4 Pharmaceuticals has published compelling first-in-human evidence demonstrating that procizumab, its proprietary monoclonal antibody, successfully reversed cardiogenic shock in three terminally ill patients within 48 hours. The data, published in the European Journal of Heart Failure, represents a significant milestone for treating a condition with mortality rates exceeding 50% and no approved causal therapies.
The publication, titled "Targeting Dipeptidyl Peptidase 3 (DPP3) in extreme-critically ill patients with refractory shock: First-in-human report on the safety and efficacy of an anti-DPP3 antibody," details the treatment of three patients with cardiogenic shock and multi-organ failure who received procizumab under named-patient use after exhausting all conventional therapeutic options.
Novel Mechanism Targets Root Cause of Shock
Procizumab is a first-in-class humanized monoclonal antibody designed to selectively target circulating dipeptidyl peptidase 3 (cDPP3), a key pathological driver of cardiogenic shock. Under normal physiological conditions, DPP3 functions as an intracellular enzyme. However, when released into circulation following cellular injury, it degrades angiotensin peptides, disrupting the renin-angiotensin-aldosterone system (RAAS) and potentially leading to cardiovascular collapse, organ failure, and death.
"With procizumab, 4TEEN4 has a tremendous opportunity to establish a biomarker-driven treatment approach in shock, an indication with mortality rates of over 50%, which to date heavily relies on symptomatic care," said Alexandre Mebaaza, MD, PhD, Professor of Medicine at Paris Cité University and lead investigator of 4TEEN4's PROCARD Phase 2a study. "Approximately half of global shock cases show elevated levels of cDPP3. Procizumab's highly specific mechanism of action has the potential to become the first treatment option to target the underlying pathological pathway of shock and address a substantial unmet medical need."
Promising Clinical Outcomes in Critical Patients
The three patients treated were terminally ill with cardiogenic shock and multi-organ failure. An independent international patient selection board confirmed that all conventional therapeutic options had been exhausted, with no further escalation possible given the high chance of immediate mortality. Each patient received a single dose of procizumab at 10 mg/kg administered over two hours.
The treatment demonstrated the expected mechanism of action through a strong reduction in DPP3 activity, accompanied by improvements across all clinical parameters assessed. These improvements included restoration of circulatory and respiratory function, reduced systemic inflammation, and normalization of kidney function. All three patients experienced shock reversal within the 48-hour follow-up period, and the treatment was well-tolerated with no adverse drug reactions.
Addressing a Critical Unmet Medical Need
Cardiogenic shock is a severe and life-threatening condition in which the heart suddenly fails to pump enough blood to meet the body's demands, leading to dangerously low blood pressure and insufficient oxygen delivery to vital organs. It represents the second most common form of circulatory failure and is most often triggered by acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF).
Shock in general affects approximately one in three ICU patients and can result from sepsis, trauma, burns, or major surgery, making it a leading cause of admission to intensive care units. Despite advances in supportive care, cardiogenic shock remains a largely unaddressed condition with no approved causal therapies and mortality rates exceeding 50%.
Clinical Development Timeline
"The results from these named-patient cases confirm the extensive body of data on the causality of elevated cDPP3 levels and increased mortality in this indication," said Andreas Bergmann, PhD, Chief Executive Officer at 4TEEN4 Pharmaceuticals. "With the first in human data, our next goal is to rapidly establish an optimal dose of procizumab in a randomized, controlled setting with our PROCARD1 Phase 2a study, aiming to enroll the first patient in the coming months."
The company's Phase 2a clinical trial of procizumab in cardiogenic shock patients is set to initiate mid-2025 at 11 centers in Europe. Following this study, 4TEEN4 is preparing for a global pivotal Phase 2/3 study, scheduled to begin in the second half of 2026.
Procizumab's safety profile has been previously established in a Phase 1 study involving healthy volunteers. The named-patient use represents the first application of procizumab in patients with cardiogenic shock, providing early human efficacy signals consistent with the company's extensive preclinical data across multiple disease models, where it effectively normalized cardiovascular parameters, reversed organ dysfunction, and increased survival.
