First Patient Treated in Phase II Combination Trial of ISA Pharmaceuticals' Lead Immunotherapy ISA101b with Keytruda®

Combination aimed at priming and driving durable patient immune responses to cancer

LEIDEN, The Netherlands, Jan. 26, 2021 /PRNewswire/ -- ISA Pharmaceuticals B.V., a clinical-stage company dedicated to developing rationally designed immunotherapeutics for oncology and infectious disease, today announced that the first patient has been dosed with its lead product ISA101b in a Phase II trial conducted and sponsored by UPMC Hillman Cancer Center, the University of Pittsburgh, PA, and supported by Merck Sharp & Dohme Corp and ISA Pharmaceuticals B.V.

The study in previously untreated patients with intermediate-risk head and neck cancer associated with human papilloma virus subtype 16 (HPV-16) will evaluate the efficacy of ISA101b and pembrolizumab (Keytruda^®) in combination with cisplatin and radiotherapy. The principal investigator is Robert L. Ferris MD, PhD, Director of UPMC Hillman Cancer Center in Pittsburgh and Associate Vice Chancellor for Cancer Research at the University of Pittsburgh School of Medicine. Dr. Ferris is a paid member of the US Scientific Advisory Board for the Merck Sharp & Dohme Corp. This study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp.

The investigator-initiated, single-arm, open-label 'Phase II Study Evaluating HPV-16 vaccination (ISA101b) and Pembrolizumab plus Cisplatin Chemoradiotherapy for Intermediate Risk HPV-16 associated Head and Neck Squamous Cell Carcinoma' aims to enroll 50 patients with end of enrollment expected in late 2022.

The primary endpoint of the trial is 2-year progression-free survival (PFS) in patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck cancer.

"For head and neck cancer patients at risk for tumor recurrence, chemo- and radiation therapy are being combined with PD-1 immune checkpoint inhibitors," said Dr. Ferris. "We seek to leverage the effect of immunotherapy to enhance T cell specific immune responses against HPV, to provide for a more profound and durable anti-tumor effect. To explore this, we have chosen the synthetic long peptide (SLP) therapeutic HPV immunotherapy ISA101b. ISA Pharmaceuticals has demonstrated that HPV, as the predominant cause of this type of cancer, harbours powerful antigens against which virus-specific T cells will mount an attack on the cancer, and we will attempt to enhance this benefit using anti-PD1 pembrolizimab."

"Currently immunotherapies combined with additional treatments are emerging as the most promising approach in oncology," said Prof. Cornelis Melief, Chief Scientific Officer of ISA Pharmaceuticals. "Consistent with this, we have demonstrated in multiple trials that ISA101b is highly synergistic with various complementary cancer treatments. Our product has shown very promising results in Phase II combination trials with standard chemotherapy¹ and the checkpoint inhibitor nivolumab². This new trial will provide valuable insights into the effect of immunomodulation in the early stage adjuvant setting, in addition to our ongoing randomized Phase II ISA101b trial with cemiplimab in late stage oropharyngeal cancer. We very much look forward to the results."

For further details of this study, please refer to https://clinicaltrials.gov/ and Identifier: NCT04369937.

About ISA Pharmaceuticals
ISA Pharma is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA Pharma has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. ISA Pharma is collaborating with Regeneron around its lead asset, ISA101b, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer. Under the terms of the collaboration, Regeneron has the option to exclusively license ISA101b. ISA101b is currently in a randomized Phase 2 clinical trial for first line and second line HPV16-positive head and neck cancer, in combination with Libtayo^® (cemiplimab), a PD-1 antibody that is being jointly developed by Regeneron and Sanofi. For more information, please visit www.isa-pharma.com.

About ISA 101b
ISA101b is a Synthetic Long Peptide (SLP^®) therapeutic designed to mount a highly specific, broad, and durable, T-cell mediated attack by the immune system on tumors positive for human papilloma virus type 16 (HPV16). The product has successfully and safely completed multiple human clinical studies in over 200 patients.

• ISA101 has been shown to be effective as monotherapy in patients with early stage, HPV16 positive, premalignant neoplasias¹.

• In late stage HPV16 positive cervical cancer, ISA101b acts favorably in synergy with chemotherapy as assessed by both size of HPV-specific immune response and clinical benefit^2,3. Late stage cancer patients suffer from local and systemic immunosuppression by immune suppressive myeloid cells, that are depleted by standard of care chemotherapy such as carboplatin and paclitaxel. This enables ISA101b to more 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 (anti-PD1 antibody) has shown tumour response rates and overall survival approximately double those seen with anti-PD1 monotherapy in 2^nd line HPV16-positive head and neck cancer⁴.
• ISA101b is protected by several patent families covering different aspects of the vaccine product. Patent protection of the vaccine product is expected until at least 2037.

ISA is currently carrying out a randomized, controlled phase 2 trial of ISA101b in combination with Libtayo in oropharyngeal cancer, under a strategic immuno-oncology collaboration with Regeneron, which was strengthened in June 2020. Further clinical trials are in preparation, including a potentially pivotal clinical trial for the combination of ISA101b and Libtayo in oropharyngeal cancer as well as a phase 2 study investigating the same combination in cervical cancer.

About HPV16 positive cancers:

• Human papilloma virus (HPV) type 16 is known to induce certain cancers such as cervical cancer and head and neck cancer
• Despite prophylactic vaccinations HPV 16 induced cancers continue to be a significant health threat with over 500,000 newly diagnosed HPV 16 positive cancer patients p.a. worldwide and over 26,000 in the USA alone.

References
¹Melief C, et al. Sci Transl Med. 2020
²Massarelli E, et al. JAMA Oncology. 2018
³Kenter G,  et al. New England J Med. 2009
⁴Welters MJ, et al. Sci Transl Med. 2016