Kovina Therapeutics Inc. today announced publication in the Proceedings of the National Academy of Sciences (PNAS) of research validating its HPV E6 targeted therapeutic approach.

The publication, “Covalent Inhibitors of Human Papillomavirus Type 16 E6 Protein Restore p53 Function and Suppress Growth of HPV-Driven Tumors in vivo,” reports that small molecules developed through Kovina’s HPV E6 program restore p53 tumor suppressor activity, induce apoptosis and senescence in HPV-positive cancer cells, and suppress tumor growth in multiple in vivo models.

HPV-associated cancers depend on sustained expression of the viral E6 oncoprotein, which mediates degradation of the tumor suppressor protein p53. Despite decades of research, E6 has remained a difficult therapeutic target.

The study included multiple controls demonstrating that compound activity is selective for HPV expressing cells. Genetic validation of mechanism was further established through an engineered E6 resistance mutation that prevented compound binding and rendered tumor cells resistant to treatment.

Key findings reported in the publication include:

• Restoration of p53 protein stability and activity in HPV-positive cancer cells
• Activation of downstream p53 transcriptional programs
• Induction of apoptosis and senescence
• Suppression of HPV-positive cervical and oropharyngeal tumor growth in vivo

“This publication validates our approach to directly targeting HPV E6 and restoring p53 function," said Kristin Sherman, Chief Executive Officer of Kovina Therapeutics. "These findings support HPV E6 as a therapeutic target and provide a strong scientific foundation for advancing our development programs in HPV-associated cancers and premalignant disease.”

The paper was published in PNAS on June 5, 2026.

Read the publication: https://doi.org/10.1073/pnas.2606213123

About Kovina Therapeutics

Kovina Therapeutics is developing first-in-class therapeutics targeting the HPV E6 oncoprotein, a key driver of HPV persistence and cancer development. The company's programs are designed to address HPV-associated disease across the continuum from premalignant lesions to invasive cancers. To learn more, visit www.Kovina.com

Funding Acknowledgment

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R44CA268137. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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