Summary:

The National Cancer Institute (NCI) seeks collaborations and licensees for a method to block PD-L1 and TGF-beta for the treatment of HPV-associated malignancies.

Description of Technology:

Advanced or relapsed human papillomavirus (HPV)-associated cancers are incurable and many of these diseases do not have a standard second line therapy. Some treatments for these diseases – such as FDA-approved immunotherapy drugs, Pembrolizumab and Nivolumab – work by blocking the PD-1 protein to assist the immune system in killing cancer cells. In addition to the PD-1/PD-L1 pathway, some data suggest the TGF-beta pathway may play a role in HPV-associated malignancies.

NCI investigators have pioneered studies in the TGF-beta pathway for the evaluation of agents for treating HPV-associated malignancies. These studies led to the invention of a method to block both PD-L1 and TGF-beta to treat HPV-associated malignancies, such as cervical cancer. The combination blockade improves response rates in patients living with HPV-associated malignancies compared to current treatments and is backed by clinical studies. While the proof of concept arose from clinical studies with bintrafusp alfa, the combination blockade approach may be achieved using various existing, repurposed or novel drug candidates and immunotherapies.

The NCI is seeking collaborations and licensees for this method that blocks PD-L1 and TGF-beta to treat HPV-associated cancers. This opportunity may be especially relevant to companies developing PD-1/PD-L1 or TGF-beta inhibitors, as it can strengthen their intellectual property stance and expand the potential use of their drug candidates to HPV-related malignancies.

Potential Commercial Applications:

• Method of inhibiting an HPV-associated malignancy in a subject administered an agent that blocks PD-L1 and TGF-beta pathways
• Method can be used to treat tumors at any stage to include tumors that have been proven to be resistant to other cancer therapies

Competitive Advantages:

• Proof-of-concept studies with bintrafusp alfa, including a Phase II trial, demonstrated significantly higher response rate in patients with HPV-associated malignancies compared to standard treatments
• This method may be practiced using various drug candidates inhibiting PD-1/PD-L1 and/or TGF-beta in combination
• This method can be further combined with anti-inflammatory agents and/or chemotherapeutic agents
• Useful in preventing, reversing, or delaying cancer progression
• Can strengthen intellectual property stance for companies developing PD-1/PD-L1 or TGF-beta inhibitors