Regeneron pairs PD-1 latecomer with ISA’s HPV immunotherapy

Regeneron and Sanofi’s PD-1 candidate cemiplimab will be tested alongside a human papillomavirus (HPV) targeting drug from Dutch biotech ISA Pharma as they play catch-up in the checkpoint inhibitor category.

The new drug—vying to become the sixth PD-1/PD-L1 drug on the market—will be twinned with ISA’s ISA101 vaccine candidate in a jointly-funded program in HPV-related cancers like cervical and head-and-neck cancer, say the two companies.

The Leiden-based company’s immunotherapy is aimed at HPV16, a strain of the virus that is thought to be responsible for 55% of human cervical cancers and premalignant lesions—cervical intra-epithelial neoplasias or CINs—and more than 60% of HPV-related head-and-neck cancers.

ISA101 is based on synthetic long peptides or SLPs, which are used to deliver oncogenic antigens in the hope of stimulating an immune response to tumors. It has already been put through its paces as a monotherapy in a proof-of-concept study published in the New England Journal of Medicine earlier this year, as well as in combination studies.

Regeneron is paying an undisclosed upfront fee for an option on ISA101, plus milestones and royalties if it decides to exercise that option and develop it for market.

The company’s head of translational science and oncology—Israel Lowy, M.D., Ph.D.—said that “early clinical results with ISA101 in HPV16-positive indications have been promising, and we're eager to investigate the impact of adding cemiplimab with the goal of further enabling the body's immune system to attack the cancer.”

Despite being a latecomer in the checkpoint inhibitor market well behind companies such as Bristol-Myers, Merck, Roche, Pfizer/Merck KGaA and AstraZeneca, Regeneron and Sanofi insist there is still room for new players.

They  are positioning cemiplimab in niche indications such as cutaneous squamous cell carcinoma (CSCC) that aren’t yet being addressed by other PD-1/PD-L1 drugs, as well as bigger targets such as non-small cell lung cancer (NSCLC) where competition will be more intense.

Novel combinations are another way to differentiate their drug candidate from the pack, but cemiplimab isn’t the first PD-1 inhibitor to be tested alongside ISA101. A phase 2 combination trial of the drug and Bristol-Myers Squibb’s Opdivo (nivolumab) in HPV-positive oropharyngeal cancer was reported at the European Society of Medical Oncology (ESMO) conference in September.

Two vaccines are already on the market to prevent HPV infections, but as yet there is no approved therapy for established HPV infections and related cancers. In fact, trials of HPV-targeting therapeutic vaccines to date have been unsuccessful, which may be a result of an unfavorable tumor microenvironment that allows HPV-related cancers to evade the immune system, according to Bonnie Glisson, M.D., of MD Anderson Cancer Center, who presented the ESMO data.

Combining vaccines such as ISA101 with checkpoint inhibitors could be the key to unlocking their efficacy, she suggested. The combination had an overall response rate of 33%, which compared favorably to the approximately 16% rate seen with Opdivo as a monotherapy in this form of cancer.