LEIDEN, the Netherlands—ISA Pharmaceuticals B.V., a private clinical-stage immunotherapy company, recently announced plans to initiate a potentially pivotal clinical trial for the combination of ISA101b and Libtayo (cemiplimab) in oropharyngeal cancer, a type of head-and-neck cancer, under its strategic immuno-oncology collaboration with Regeneron. In addition, Regeneron will increase its equity stake in ISA Pharmaceuticals.
The new oropharyngeal cancer trial is the third trial planned under the clinical collaboration between ISA Pharmaceuticals and Regeneron. ISA101b, an immunotherapy targeting human papillomavirus type 16 (HPV16), is currently in a Phase 2 clinical trial for first- and second-line HPV16-positive head-and-neck cancer in combination with Libtayo, a PD-1 inhibitor that is being jointly developed by Regeneron and Sanofi.
A second Phase 2 trial investigating the same combination in cervical cancer is also planned. More than 60 percent of head-and-neck cancers and approximately 55 percent of cervical cancers are HPV16-induced.
“This agreement will accelerate the development and commercialization of our lead asset, ISA101b, to treat two important cancers with high unmet medical needs,” said Gerben Moolhuizen, CEO of ISA Pharmaceuticals. “We are extremely pleased to be working with Regeneron and for their continued support of both ISA pharmaceuticals and our clinical studies in both indications.”
Under the revised agreement, the clinical collaboration offers a potential shortened path to first approval in the HPV16-positive oncology indications being studied in the next few years. The agreement also streamlines ISA Pharmaceuticals’ access to license fees, milestone payments and royalties. Together with a recently secured loan from the European Investment Bank, development of ISA101b is now fully funded through the data readout of ongoing and planned pivotal trials which will support regulatory filings, according to ISA.
“Thanks to this updated clinical collaboration, we are able to rapidly diversify our research into a broader array of HPV16-induced cancers,” commented Dr. Israel Lowy, Regeneron’s senior vice president of translational and clinical sciences, oncology. “ISA101b offers a validated mechanism of action, and we look forward to working with ISA Pharmaceuticals to determine the synergistic potential of combining this novel immunotherapy with Libtayo to better address these difficult-to-treat cancers.”
ISA101b is a synthetic long peptide therapeutic designed to mount a highly specific T cell-mediated attack by the immune system on tumors positive for HPV16. The product has successfully and safely completed multiple human clinical studies in more than 200 patients. ISA101 has shown effectiveness in patients with early-stage, HPV 16-positive, premalignant cancers, the companies say.
In late-stage, HPV16-positive cervical cancer, ISA101b reportedly has been shown to act complementary to chemotherapy in terms of clinical benefits. Late-stage cancer patients suffer from local and systemic immunosuppression by immune suppressive myeloid cells. Standard-of-care chemotherapy regimens such as carboplatin and paclitaxel deplete these immunosuppressive cells while also having a direct antitumor effect, and further enable ISA101b to effectively attack the cancer via a T cell-mediated immune response.
Importantly, in a Phase 2, open-label, proof-of-concept study, ISA101b in combination with nivolumab (an anti-PD1 antibody) has shown tumor response rates and overall survival approximately double those seen with anti-PD1 monotherapy in second-line head and neck cancer positive for HPV16.