First-in-Human Study: Amplivant® Adjuvant Boosts Immune Response of Synthetic Long Peptide Immunotherapy

• First-in-human study investigating the safety and immunogenicity of ISA's proprietary Amplivant adjuvant conjugated to human papillomavirus type 16 (HPV16) Synthetic Long Peptides (SLPs).
• SLPs conjugated to Amplivant elicit a significant, strong immune response and dose related systemic T cell immunity when injected intradermally.
• Study demonstrates that SLPs conjugated to Amplivant have highly favourable tolerability and safety when used as an intradermal therapeutic vaccine.

OEGSTGEEST, The Netherlands, Nov. 8, 2022 /PRNewswire/ -- ISA Pharmaceuticals B.V., a clinical stage biotech company developing immunotherapies to treat cancers and infectious diseases, is delighted to announce publication by Leiden University Medical Center (LUMC) of a phase 1 clinical study using ISA's proprietary Amplivant^® adjuvant and Synthetic Long Peptide (SLP^®) therapeutic vaccine technology. The study was recently published in the Journal for ImmunoTherapy of Cancer. This open access paper is entitled 'Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV16 positive (pre-)malignant lesions' and can be found at: https://doi.org/10.1136/jitc-2022-005016.

Amplivant is a molecularly optimized Toll-like receptor 1/2 ligand that can be covalently conjugated to tumour peptide antigens. In preclinical models Amplivant-adjuvanted SLPs strongly enhance antigen presentation by dendritic cells, T cell priming, and induce effective antitumor responses.

This first-in-human clinical study demonstrated a favourable safety profile without serious adverse events and a strong immune response generated with only two Amplivant-conjugated HPV16 SLPs. The study concludes that Amplivant-conjugated SLPs can be safely used as an intradermal therapeutic vaccine to induce HPV16-specific T cell immunity in previously treated patients with HPV16-positive (pre-)malignancies. Vaccine dose escalation in 25 patients caused a corresponding increase in systemic T cell immunity.

Amplivant was conjugated to two SLPs derived from the two most immunodominant regions of the HPV16 E6 oncoprotein. Patients received 3 doses intradermally, three times a week, and with a 3-week interval in four dose groups (1, 5, 20 or 50 µg per conjugated peptide). Peptide-specific T cell immune responses were determined in PBMC's from blood samples taken before, during and after vaccination.

Details of the study can be found on clinicaltrials.gov under the identifier NCT02821494.

About ISA Pharmaceuticals

ISA Pharmaceuticals is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. Its lead asset ISA101b is in late-stage clinical trials for human papillomavirus type 16 (HPV16)-induced cancers in a collaboration with biotechnology company Regeneron.

Other assets are in preclinical stage development and include immunotherapies to treat patients that suffer from cancers that over-express PRAME, chronic hepatitis B or SARS-CoV2 infections. For more information, please visit www.isa-pharma.com.

About AMPLIVANT^®

ISA's AMPLIVANT^® technology comprises a proprietary and synthetic Toll-Like Receptor (TLR) 1/2 ligand with enhanced immunostimulatory activity that can be coupled to the peptide in the standard SLP^® manufacturing process. AMPLIVANT^®-conjugated immunotherapeutics allow lower dosing at higher efficacy through better dendritic cell antigen processing and presentation as well as enhanced T cell priming.

This technology is not only applicable to all SLP^® immunotherapeutics, but also to any other type of targeted immunotherapy to potentially enhance treatment efficacy.

AMPLIVANT^® is registered as a trademark in Europe.