Zymedi's Rapaprutug: A New Name and New Hope for PAH Treatment

INCHEON, South Korea – December 08, 2025 – For the small but resilient community of patients with pulmonary arterial hypertension (PAH), any step forward in the long journey of drug development feels monumental. Today marks one such step. South Korean biopharmaceutical firm Zymedi announced that its first-in-class antibody therapy, ZMA001, has officially been assigned the International Nonproprietary Name (INN) "rapaprutug" by the World Health Organization (WHO).

While the assignment of a generic name might seem like a procedural formality, it is a critical milestone that signals a drug's maturation from a laboratory compound to a serious clinical contender. For Zymedi, a company built on pioneering science around aminoacyl-tRNA synthetases (ARSs), this global designation provides a unified identity for its lead candidate as it progresses through human trials. Rapaprutug is not just another drug for PAH; it represents a potential paradigm shift, moving beyond symptom management to target the underlying inflammatory and fibrotic drivers of this devastating disease.

"We are very pleased that the WHO has designated the nonproprietary name rapaprutug for our lead PAH program," said Sunghoon Kim, CEO and Founder of Zymedi. "This milestone underscores our team's long-term efforts to discover and develop innovative biologic therapies that address the root causes of macrophage-driven inflammatory and fibrotic diseases... We remain committed to bringing meaningful treatments to patients worldwide."

A New Attack on an Old Foe

Pulmonary arterial hypertension is a rare, progressive, and life-threatening condition affecting an estimated 3 in every 100,000 people. It is characterized by the severe narrowing of the arteries that carry blood from the heart to the lungs. This creates immense resistance, forcing the right side of the heart to work harder, eventually leading to right-ventricular failure and death. For decades, the standard of care has revolved around vasodilation—using drugs to relax and widen these constricted blood vessels.

Therapies like prostacyclin analogues, endothelin receptor antagonists (ERAs), and PDE-5 inhibitors (such as sildenafil) have been invaluable in improving symptoms and quality of life. However, they do not halt the underlying disease progression. The core pathology of PAH involves complex vascular remodeling, inflammation, and fibrosis, processes that current treatments fail to adequately address. This leaves a significant unmet need for disease-modifying therapies that can tackle the root cause.

This is where rapaprutug aims to redefine the treatment landscape. Developed from the groundbreaking ARS research of Zymedi's founder, Dr. Sunghoon Kim—a renowned scientist with a PhD from Brown University and postdoctoral experience at MIT—the drug employs a novel mechanism of action. Rapaprutug is a human monoclonal antibody that targets a specific protein called lysyl-tRNA synthetase 1 (KARS1) when it appears on the surface of immune cells called monocytes.

Under inflammatory conditions like those found in PAH, KARS1 moves to the cell membrane, acting as a beacon that triggers the infiltration of these monocytes into lung tissue, where they differentiate into inflammation-inducing macrophages. These macrophages are key drivers of the vascular damage and fibrosis that define PAH. Rapaprutug works by binding to this exposed KARS1, effectively neutralizing the signal and preventing these destructive immune cells from being recruited to the lungs. Crucially, it does so without interfering with KARS1's essential intracellular function in protein synthesis, suggesting a highly targeted approach with potentially fewer side effects than systemic anti-inflammatories.

Building a Strategic Moat Around Innovation

The journey from a scientific concept to a marketable drug is fraught with financial and regulatory hurdles. Zymedi, which has secured over $29 million in funding, appears to be navigating this path with strategic precision. The INN assignment is the latest in a series of calculated moves that de-risk rapaprutug's development and bolster its market potential.

In July 2024, the U.S. Food and Drug Administration (FDA) granted rapaprutug Orphan Drug Designation (ODD). This status is reserved for therapies treating rare diseases affecting fewer than 200,000 Americans and provides powerful incentives. These include seven years of market exclusivity post-approval, federal tax credits on clinical trial costs, and a waiver of the substantial PDUFA fees required for a new drug application. This designation not only provides a financial cushion but also offers a clearer, more collaborative regulatory pathway with the FDA.

Furthermore, Zymedi's development is supported by a Collaborative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health (NIH), specifically the National Heart, Lung, and Blood Institute (NHLBI). This partnership is a significant validation of Zymedi's science, lending the institutional weight and world-class clinical infrastructure of the NIH to the drug's early-stage development. The ongoing Phase 1 clinical trial is being conducted at the NIH Clinical Center, a testament to the strength of this collaboration.

The Clinical Path Forward

With a formal name and key regulatory designations secured, all eyes are now on rapaprutug's clinical performance. The first-in-human Phase 1 study (NCT05967299), which dosed its first healthy volunteer in February 2024, is designed to evaluate the drug's safety, tolerability, and pharmacokinetics across single ascending doses. This foundational trial will establish a safe dosage range before advancing to studies in patients.

Zymedi has indicated that it plans to initiate Phase 2a trials in PAH patients in the second half of 2025. This next stage will be the first true test of rapaprutug's efficacy, moving from safety in healthy individuals to demonstrating a therapeutic effect in those living with the disease. Preclinical data has been promising, showing that the antibody not only improved key PAH parameters and survival rates in animal models but also exhibited a synergistic effect when combined with sildenafil, a current standard of care. This suggests rapaprutug could potentially be used both as a monotherapy and as a powerful addition to existing treatment regimens.

For an industry accustomed to incremental advances, a first-in-class, disease-modifying agent like rapaprutug represents a significant leap. As Zymedi prepares for the critical transition to patient trials, the global medical community will be watching closely to see if this innovative approach can deliver on its promise to finally alter the course of pulmonary arterial hypertension.