Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models

Lieber, C. M.; Wolf, J.; Govindarajan, M.; Yoon, J.; Sticher, Z. M.; Ruckel, C.; Leach, A.; Harrison, L.; Vyshenska, D.; Cruz, A.; Andrews, M.; Krueger, R.; Cox, R.; Painter, G. R.; Greninger, A. L.; Natchus, M. G.; Plemper, R. K.

doi:10.64898/2025.12.21.695822

bioRxiv · 10.64898/2025.12.21.695822

Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models

Lieber, C. M.·Wolf, J.·Govindarajan, M.·Yoon, J.·Sticher, Z. M.·Ruckel, C.·Leach, A.·Harrison, L.·Vyshenska, D.·Cruz, A.·Andrews, M.·Krueger, R.·Cox, R.·Painter, G. R.·Greninger, A. L.·Natchus, M. G.·Plemper, R. K.

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Abstract

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 development of clinical candidate analog GHP-88310 (EIDD-3608), which combines improved oral efficacy with favorable tolerability in non-rodents (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 2,000 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 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.

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Lieber, C. M., Wolf, J., Govindarajan, M., Yoon, J., Sticher, Z. M., Ruckel, C., Leach, A., Harrison, L., Vyshenska, D., Cruz, A., Andrews, M., Krueger, R., Cox, R., Painter, G. R., Greninger, A. L., Natchus, M. G., Plemper, R. K.. 2025-12-22. Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models. https://doi.org/10.64898/2025.12.21.695822

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