Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models
- Carolin M. Lieber
- Josef D. Wolf
- Mugunthan Govindarajan
- Jeong-Joong Yoon
- Zachary M. Sticher
- Claire E. Ruckel
- Alexander I. Leach
- Lauren A. Harrison
- Dariia Vyshenska
- Amalia A. Cruz
- Meghan K. Andrews
- Rebecca E. Krueger
- Robert M. Cox
- George R. Painter
- Alexander L. Greninger
- Michael G. Natchus
- Richard K. Plemper
2026-05-22
Orthoparamyxoviruses, such as human parainfluenza virus type 3 (HPIV3) and measles virus (MeV), are a major health threat. We discovered an orally efficacious broad-spectrum inhibitor of orthoparamyxovirus polymerases. However, here, we found that tolerability in higher mammals was limited. We report the development of the clinical candidate analog GHP-88310 (EIDD-3608), which combines improved oral efficacy with favorable tolerability in nonrodents (ferrets and dogs). GHP-88310 was active against HPIV3, Sendai virus (SeV), MeV, and related canine distemper virus (CDV). In 7-day tolerability studies, daily doses of 2000 mg/kg were well tolerated. Pharmacokinetic analysis revealed altered plasma exposure of GHP-88310 compared to the original hit. In HPIV3-infected cotton rats, GHP-88310 lowered the respiratory tract viral load. Dosing of ferrets infected with CDV, causing lethal measles-like disease, resulted in complete survival, reduction of viremia and shed viral load, and alleviated lymphocytopenia. Once-daily GHP-88310 was efficacious in the CDV-ferret and HPIV3-cotton rat models. The compound was sterilizing against HPIV3 at physiological concentrations in human airway epithelium organoids.