ISA Pharmaceuticals announces start of first Phase I/II clinical trial of its SLP®-AMPLIVANT® conjugates

March 02, 2015

• Leiden University Medical Center to study novel immunotherapeutic in HPV-positive head & neck cancer patients

Leiden, The Netherlands, February 26, 2015 – ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, has announced the start of an investigator-initiated Phase I/II clinical trial of a novel immunotherapeutic based on ISA Pharmaceuticals´ platform technology. The trial will be conducted by the Department of Clinical Oncology at Leiden University Medical Center in The Netherlands. The study will investigate the biological activity and safety of the compound in head and neck cancer patients who tested positive for human papilloma virus type 16 (HPV16). HPV infections, in particular HPV16, are one of the major causes of this type of cancer. The immunotherapeutic is a conjugate of two HPV16 E6 Synthetic Long Peptides (SLP®s) covalently linked to AMPLIVANT®, a synthetic Toll-like receptor (TLR) 1/2 ligand. The investigators have assigned the acronym HESPECTA to the conjugate (HPV E-Six Peptide Conjugated To AMPLIVANT®).

In the single-center, open-label dose escalation study, 24 HPV16-positive head and neck cancer patients will be grouped into four dose escalation groups. In each group, every patient will receive three intradermal doses of the immunotherapeutic. The primary endpoint is to assess its ability to induce HPV16 E6-specific T-cell immunity. The secondary endpoint is to evaluate the safety of the intervention.
The human papillomavirus is associated with several types of cancer, of which HPV16 is by far the most common high-risk HPV type detected. It encodes the two tumor-specific oncoproteins E6 and E7 which are known to also induce and maintain the malignant state of the transformed cells. This SLP®-AMPLIVANT® conjugate aims to induce a strong, lasting immune response against the tumor.

“We have already demonstrated in earlier studies that unconjugated HPV16 SLPs in the presence of adjuvants are safe and highly immunogenic in patients with HPV-induced lesions and cancers,” said Prof. Cornelis Melief, CSO of ISA Pharmaceuticals. “We have conjugated the two most immunoactive peptides representing the most immunogenic regions of the HPV16 oncogenic antigens to our proprietary AMPLIVANT immune stimulant. We expect even stronger and more effective anti-tumor T-cell responses as a next generation treatment."

“We are looking forward to the first clinical validation of our AMPLIVANT immune stimulant,” said Ronald Loggers, CEO of ISA Pharmaceuticals. “We know from our preclinical studies that SLP-AMPLIVANT conjugates allow lower dosing and higher efficacy due to better dendritic cell antigen processing and presentation, as well as enhanced T cell priming. This technology can not only be applied to all SLP immunotherapeutics, but also to any other type of targeted immunotherapy, significantly enhancing its efficacy.”
AMPLIVANT®, developed by ISA Pharmaceuticals, is based on a Toll-like receptor ligand (TLR1/2 ligand), one of the most powerful natural stimulants of the immune system. SLP®-AMPLIVANT® conjugates have demonstrated to be 100- to 1000-fold more potent in inducing an immune response compared to unconjugated SLP®s in preclinical and mouse tumor models.

About ISA Pharmaceuticals

ISA Pharmaceuticals B.V. is an immunotherapy company developing rationally designed, fully synthetic immunotherapeutics against cancer and persistent viral infections. The company has built a proprietary immunotherapy platform based on the Synthetic Long Peptide (SLP®) concept and AMPLIVANT® technology, which enable the generation of safe and effective drugs with a known mechanism of action. Synthetic long peptides are broadly applicable to multiple targets and ideally suited for monotherapy, as essential components in combination with conventional cancer treatments, and as novel immunomodulators. SLP® immunotherapies are capable of fully harnessing and directing the body‘s own defenses towards fighting the disease.

ISA101, an SLP® immunotherapy targeting human papillomavirus (HPV)-induced diseases, is currently in clinical development in cervical cancer and anal intraepithelial neoplasia (AIN). Clinical proof-of-concept has been established with ISA101 in vulvar intraepithelial neoplasia (VIN), a pre-cancerous disease caused by HPV.

The company was founded in 2004 by Aglaia Oncology Fund and is based in Leiden, The Netherlands. For more information, please visit www.isa-pharma.com

SLP® and AMPLIVANT® are registered trademarks in Europe.