– Three additional European patents and market exclusivity granted for the use of key active ingredients of ISA101
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced it has strengthened the IP position of its lead compound ISA101. The European Patent Office has granted three patents (EP2267132, EP2112157, EP2468763) which relate to the use of HPV antigen-based peptides. ISA101, a novel immunotherapeutic consisting of synthetic long peptides (SLP®s), targets severe diseases triggered by human papillomavirus (HPV) infection.
The patents cover the application of a variety of long peptides derived from the E6 and E7 proteins of HPV, including novel epitopes or peptides with specified features, and provide exclusivity for the treatment of persistent HPV infections and resulting diseases.
ISA101 is based on ISA Pharmaceuticals´ proprietary SLP® platform and is currently in clinical Phase I/II trials in cervical cancer and anal intraepithelial neoplasia (AIN).
– SLP®s modulate intratumoral macrophages required for tumor regression
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced the publication of a new peer-reviewed paper* demonstrating a beneficial effect of Synthetic Long Peptide (SLP®s) immunotherapeutics on intratumoral macrophages in cancers induced by human papilloma virus 16 (HPV16). ISA’s proprietary SLP® immunotherapeutics are rationally designed, off-the-shelf, synthetic peptides which ISA is developing as cancer immunotherapeutics. The company’s SLP® lead compound ISA101 is in clinical development for the treatment of early-stage, advanced and recurrent cancers induced by HPV16 infections.
Macrophages, a type of white blood cell, play a critical role in immunity by recruiting other immune cells and exerting effector functions, such as phagocytosis and cell or bacterial killing. They exist in two major and opposing types: The so-called M1 macrophages inhibit cell proliferation and cause tissue damage, while M2 macrophages promote cell proliferation and tissue repair. Cancer is often characterized by M2 activity, which facilitates tumor growth via angiogenesis, metastasis formation and suppression of Th1-type immune responses, among others. As a result, M2 macrophage infiltration of tumors commonly correlates with poor prognosis.
Based on these observations, the targeting of macrophages or inhibition of macrophage infiltration is considered a promising therapeutic option in cancer therapy. However, as part of an ongoing investigation into tumor immunotherapy, the authors of the paper cited below were able to demonstrate that skewing the macrophages towards M1 antitumor activity might be the optimal strategy instead. In animal studies, this skewing can be accomplished with ISA’s Synthetic Long Peptide (SLP®) immunotherapeutics.
The team of researchers used a mouse tumor model of HPV-induced cancers, such as cervical cancer, and HPV-positive head and neck cancer. Administration of an SLP® compound, among others, resulted in an influx of cytokine-producing CD8 T cells that strongly altered the numbers and phenotype of intratumoral macrophages from M2 to M1 activity. It was also demonstrated that complete regressions of large established tumors are dependent on the tumor-infiltrating macrophages induced by this immunotherapy: when a small molecule drug inhibitor diminished the number of intratumoral macrophages after SLP® administration, the complete remissions were abrogated and survival rates deteriorated.
* van der Sluis TC et al. (2015), Therapeutic peptide vaccine-induced CD8 T cells strongly modulate intratumoral macrophages required for tumor regression. Cancer Immunol Res. 2015 Apr 17. pii: canimm.0052.2015
– Intradermal administration provides significant benefits compared to subcutaneous application
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced it has been granted a European patent (patent no. EP 2 155 240) for the intradermal administration of synthetic long peptides (SLP®s) based on HPV oncogenes, including its lead compound ISA101.
Specifically, the patent was granted for the therapeutic use of intradermally delivered long peptides derived from the E2, E6 and/or E7 proteins of the human papillomavirus (HPV) to treat or prevent HPV-related diseases.
ISA101 is a clinical-stage immunotherapeutic for the treatment of early-stage, advanced and recurrent cancers induced by HPV16 infections and is based on ISA Pharmaceuticals´ proprietary SLP® platform. The compound is currently in clinical Phase I/II trials in cervical cancer and anal intraepithelial neoplasia (AIN).
As shown in healthy volunteers, intradermal administration of low doses of the HPV16 E6 and E7 SLP® without any adjuvant resulted in an effective, long-lasting systemic T cell response. This shows that, compared to subcutaneous delivery, the new epidermal routing with lower doses and absence of a concomitant adjuvant is also capable of eliciting a robust immune response in naïve individuals.
– Experiments to evaluate a novel nasal cervical cancer immunotherapeutic
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced that its fully-owned subsidiary ISA Therapeutics B.V. has closed an R&D agreement with Japan-based Shin Nippon Biomedical Laboratories, Ltd. (SNBL) to explore a novel nasal delivery for ISA’s cervical cancer immunotherapeutic. In the experiments, ISA Pharmaceuticals’ proprietary Synthetic Long Peptide (SLP®) immunotherapeutic ISA101 will be administered via SNBL’s novel nasal drug delivery technology. SNBL´s patent-protected approach is designed to significantly enhance the absorption of powder-based nasal drugs from the nasal mucosa.
Both parties expect to obtain basic research data on a potential antigen-specific immune response.
ISA101 is ISA Pharmaceuticals´ most advanced pipeline program and designed to treat early-stage, advanced and recurrent cancers induced by HPV16 infections. ISA101 is currently administered via subcutaneous injections and has successfully completed several clinical studies in the Netherlands and Belgium for advanced and recurrent cervical cancer, as well as other early-stage HPV16-related cancers.
ISA101 consists of 13 synthetic long peptides (25-35 amino acids long) derived from the E6 and E7 oncogenic proteins of the HPV16 virus. This strain is responsible for 50% of human cervical cancers and cervical intra-epithelial neoplasias and for more than 85% of HPV-positive head and neck cancers, anal cancers and premalignant HPV-induced anal lesions (termed anal intra-epithelial neoplasia, or AIN).
In the United States, cervical cancer is the second most common cancer in women after breast cancer. In Japan, approximately 10,000 women are diagnosed for cervical cancer, and approximately 2,700 infected women die from the disease every year. Since HPV can remain persistent in the body for over a decade before cancer develops, there is a strong demand not only for prophylactic vaccines preventing HPV infections, but also for novel immunotherapeutics to treat already infected individuals.