HPV-E7 Protein Degrader

About RDP Pharma AG

RDP Pharma AG is a privately held biotech dedicated to the vision that their products will deliver valuable medicines to patients in need.

RDP’s leadership team and board of directors are focused on getting their products into clinical trials and addressing the unmet medical needs of patients. The team comprises entrepreneurs, drug development experts, and biotech veterans. Their extensive experience ensures that the right questions are asked, the right experiments conducted, and the right clinical studies implemented.

About HPV E7 Oncoprotein

RDP has identified a first-in-class, orally available, small molecule-based, new chemical entity (NCE) which induces the proteolysis of the human papillomavirus (HPV) associated E7 oncoprotein.

The lead E7 compound was selected from more than 64 million compounds employing computer cavity docking simulations (in silico screens). Following selection, 1,000 molecules were chemically synthesized and tested using a proprietary E7 assay. Single-agent efficacy of VS035 has been demonstrated in an HPV-dependent cervical cancer xenograft model. The compound reveals clear single-agent inhibition of E7 activity, where no toxicity was observed in mice studies. VS035 decomposes E7, thereby stopping uncontrolled cell division, ceasing tumour-induced cell signaling and re-activating the adaptive immune response.

It is anticipated that HPV-induced malignancies, such as cervical, vulvar, or anal intraepithelial neoplasia, could be treated with our lead compound as monotherapy. Invasive cancers shall benefit from VS035 in combination with chemotherapies and/or PD1 inhibitors. These treatment schemes are expected to be a significant positive impact, including HPV-induced cancer in advanced stages.

Specifications for Inhibitor Selection

• Clear activity in HPV-induced xenograft model
• Oral availability and favorable pharmacokinetics
• Ability to decompose E7 within its in vivo half-life
• Low toxicity
• Compliance with the “Lipinski rule of 5” (drug-ability)
• Ease of synthesis and favorable upscaling properties
• Good patentability (new composition of matter patent and beyond)

Experiments demonstrating the degradation of E7. The read-out for the screen was the degradation of E7 primary screen: flow cytometry, cycloheximide [CHX] was the positive control; a shift to the left indicates degradation of E7 – secondary screen: E7 protein steady-state levels under treatment.