GEn1E Lifesciences Unveils Dual Signal Modulators in Anti-inflammatory Therapies

On October 14, 2024, GEn1E Lifesciences, a clinical-stage company in the Phase 2 stage, announced a significant breakthrough in the realm of precision therapies for inflammatory and rare diseases. This prominent advancement, achieved in collaboration with the University of Maryland, Baltimore (UMB), was published in the Journal of Pharmacology and Experimental Therapeutics (JPET).

The study, titled "First-in-Class Mitogen-Activated Protein Kinase p38α: MAPK-Activated Protein Kinase-2 (MK2) Dual Signal Modulator with Anti-inflammatory and Endothelial-Stabilizing Properties," represents a notable stride in the development of next-generation immunomodulatory treatments for inflammatory and autoimmune diseases.

Professor Paul Shapiro, PhD, who co-authored the study and serves as a faculty member in the Department of Pharmaceutical Sciences at the University of Maryland School of Pharmacy, emphasized the transformative nature of their findings. He explained that previous clinical failures of p38 catalytic inhibitors were likely due to inherent flaws in the approach of inhibiting kinase activity. By employing a novel strategy focused on the structure and functions of the p38 MAPK, the researchers were able to modulate vital inflammatory pathways while reducing off-target effects. This innovative approach holds the potential to revolutionize the treatment of inflammatory diseases.

Dr. Jeff Hasday, a co-contributing author of the study and the Dr. Herbert Berger Professor of Medicine at the University of Maryland School of Medicine, highlighted the clinical significance of the findings. He explained that the compound GEn-1124 offers a precise mechanism to disrupt the p38:MK2 complex without inhibiting p38's catalytic activity, thereby balancing downstream pro- and anti-inflammatory signaling. This results in anti-inflammatory, endothelial-stabilizing, and lung-protective effects, which could be particularly beneficial in treating pulmonary diseases characterized by inflammation and endothelial barrier dysfunction.

Key aspects of the study include:

1. **Targeted Modulation**: GEn-1124 specifically disrupts the p38α:MK2 complex while preserving essential downstream signaling for cellular function, selectively inhibiting pro-inflammatory responses.

2. **Efficacy in Preclinical Models**: The compound demonstrated significant efficacy in preclinical studies, improving survival rates by a factor of four in acute lung injury and five in influenza-induced pneumonia. It also showed potential to halt disease progression.

3. **Endothelial-Stabilizing Properties**: GEn-1124 exhibited strong barrier-stabilizing effects in human pulmonary artery endothelial cells (hPAECs), a critical aspect in treating diseases with vascular leakage and inflammation.

The findings are timely as GEn1E Lifesciences is currently enrolling patients for a Phase 2 study focused on Acute Respiratory Distress Syndrome (ARDS), a severe condition with a substantial economic impact on the US healthcare system.

Ritu Lal, CEO and Co-founder of GEn1E Lifesciences and adjunct Associate Professor at the University of Maryland School of Pharmacy, expressed excitement about the study's potential. She emphasized that this breakthrough aligns with the company’s mission to develop precision therapies for inflammatory diseases and improve patient outcomes.

GEn1E Lifesciences, headquartered in Palo Alto, California, with a laboratory in Mountain View, California, is a clinical-stage Phase 2 company dedicated to accelerating the development of novel precision therapies for rare and inflammatory diseases. The company employs an AI-driven "Platform-in-a-Mechanism" model that encompasses the entire drug development cycle, enabling the rapid advancement of first-in-class therapies for these conditions.