– Targeting and Activating Dendritic Cells is the Key to Success

Leiden, The Netherlands, March 11, 2016 – ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company, has announced the publication of a review of cancer immunotherapies in Nature Reviews Cancer [1] that outlines strategies to overcome immune evasion by tumors. The publication was co-authored by a team of researchers from Leiden University Medical Center (LUMC) and ISA Pharmaceutical’s’ CSO Kees Melief.

Cancer immunotherapies have a mixed track record. While challenging the immune system via tumor antigens by raising tumor-specific T cells is successful in most cases, this strategy often does not cause T cells to zero in on tumor cells and exert their function within the tumor. Such failures demonstrate the overwhelming ability of cancers to protect themselves by suppressing the immune system, escaping mechanisms via cell-intrinsic factors and controlling their microenvironment. Cancer immunotherapies have successfully eradicated tumor cells only in a setting where immunosuppression was less evident or counteracted by successful measures such as checkpoint blocking.

This review of nearly 250 peer-reviewed publications demonstrates that successful immunotherapies rely on a number of important factors:

• Selection of tumor-associated antigens (should be virus-related in virus-induced cancers or, in cancers of other origins, preferably neo-antigens arising from mutations)
• Induction of robust and balanced CD4/CD8+effector and memory T cell responses by a suitable immunotherapy platform
• Parallel targeting of the immunosuppressive cancer environment via selected co-treatments, e.g. chemotherapy or checkpoint blocking

“Optimal therapeutic activity relies on immunotherapeutics that simultaneously target and activate dendritic cells, thereby eliciting robust type I oriented CD4+ and CD8+ T cell responses,” said Kees Melief, CSO of ISA Pharmaceuticals and co-author of the review. “In settings of premalignant disease, carcinoma in situ or minimal residual disease, immunotherapeutic vaccines are clinically successful as a monotherapy. However, in progressive cancers, co-treatments are required to overcome immune evasion and to achieve full efficiency. In this setting, immunotherapeutic vaccines will become valuable by increasing the effects of standard chemotherapies, checkpoint blocking and other therapies.”

“The review clearly validates our strategy of addressing HPV-induced malignancies with an off-the-shelf monotherapy of synthetic long peptides (SLPs), and of targeting other cancers via personalized SLPs based on patient-derived neo-antigens”, said Ronald Loggers, CEO of ISA.

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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 have the potential to generate safe and effective immunologic responses 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 with novel immunomodulators such as Nivolumab. SLP^® immunotherapies are designed to fully harness and direct the body’s own defenses towards fighting the disease. In addition, ISA has begun to develop personalized SLP^® immunotherapies targeting tumor-specific, mutation-derived neo-antigens. These SLP^®s are based on the analysis of specific DNA mutations in a tumor sample, and designed and synthesized for each individual patient.

ISA´s most advanced clinical-stage immunotherapeutic is ISA101, an SLP^® immunotherapy targeting human papillomavirus (HPV)-induced diseases. It is currently in clinical development in advanced and recurrent cervical cancer, incurable HPV16-postive solid tumors and anal intraepithelial neoplasia (AIN). Clinical proof-of-concept has been established 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.

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[1] Van der Burg SH et al. 2016. “Vaccines for established cancer: overcoming the challenges posed by immune evasion.” Nat Rev Cancer (in press; advance online publication: March 11, 2016); doi:10.1038/nrc.2016.16

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