– Synthetic Long Peptide (SLP^®) immunotherapy achieves targeted tumor eradication comparable to checkpoint-blocking immunotherapy

– New findings on antigens relevant for checkpoint blocking pave the way for personalized cancer vaccines

Leiden, The Netherlands, November 27, 2014 – ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced that a recent scientific paper in Nature supports the company´s therapeutic approach to using synthetic long peptides in cancer therapy. It could be shown that personalized SLP^® immunotherapy is as capable of inducing efficient tumor eradication as are T cell checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 monoclonal antibodies. The research was conducted by a consortium led by Prof. Robert D. Schreiber from Washington University St. Louis. Prof. Cornelis Melief, Willem-Jan Krebber, and Gwenn E. Mulder from ISA Pharmaceuticals also participated in the project.

It is well known that checkpoint immune regulators on the surface of T cells act as deactivators. While they are useful in preventing T cells from attacking healthy tissues, in cancer they prevent the T cells from destroying tumor cells. Checkpoint blockers, such as anti-PD-1 and anti-CTLA-4 monoclonal antibodies, that target these proteins are very effective in restoring the T cell’s ability to eradicate tumor cells. In the Nature publication, Matthew M. Gubin and co-workers – among them three ISA researchers – report about their identification of the antigens recognized by these tumor-infiltrating T cells once their activity has been restored. The researchers used a mouse model of carcinogen-induced cancer, which – like human lung cancer from smokers – bears many mutations (e.g. caused by tar).

The researchers demonstrated that the T cells previously blocked by checkpoint immune regulators were directed against two mutant antigens on the cancer cell surface. These T cells had already infiltrated the tumor prior to checkpoint blocking, but were subsequently deactivated by the tumor microenvironment. Moreover, the team showed that an immunotherapy consisting of two synthetic long peptides, each incorporating one of the mutant amino acid sequence admixed with the adjuvant poly I:C, was able to eradicate the tumor as effectively as checkpoint immunotherapy.

“These findings offer important mechanistic insights into the mode of action of checkpoint immune regulators, and point the way towards personalized approaches based on the SLP^® immunotherapy concept,” said Prof. Cornelis Melief, Chief Scientific Officer of ISA Pharmaceuticals. “Checkpoint blocking is capable of activating existing inert T cells against mutant antigens. Now we know that an adjuvanted SLP^® immunotherapy with similar anti-tumor effects as checkpoint immunotherapy can be created.”

Personalized synthetic long peptides against tumor-unique mutant sequences are a promising treatment approach for cancers with many mutations, such as smoking-induced lung cancer and UV-induced skin cancer. Compared to checkpoint blocking, personalized immunotherapy is likely to achieve anti-tumor effects with less toxicity because they do not activate T cells that are able to attack healthy tissue.

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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

AMPLIVANT® is a registered trademark in Europe.

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