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Company News: Anergis Reports Positive Phase IIb Data for Birch Pollen Allergy Vaccine AllerT
– AllerT 50 μg meets primary and secondary endpoints
– Vaccine improves quality of life and symptom scores
Anergis, a company focusing on proprietary allergy vaccines, reported today that a Phase IIb study of its lead compound AllerT met the primary endpoint of reducing the combined symptom and medication score with AllerT 50 μg during the birch pollen season. Moreover, the vaccine improved the quality of life and symptom scores with AllerT 50 μg and AllerT 100 μg. AllerT is a birch pollen allergy vaccine derived from the company´s proprietary Contiguous Overlapping Peptide (COP) technology platform, which is designed to provide ultra-fast allergy desensitization after only two months of treatment.
In a placebo-controlled, double-blind, randomized multicenter trial, a total of 240 patients from 24 trial centers in Switzerland, France, Poland, Latvia, Lithuania, Sweden and Denmark were divided into three groups (placebo, AllerT 50 μg and AllerT 100 μg, respectively). From November 2012 to March 2013, the patients received 5 injections over a period of 2 months as a pre-seasonal treatment.
During the subsequent 2013 birch pollen season, compared to the placebo group, the combined Rhinoconjunctivitis Symptom and Medication Score (RSMS, primary endpoint) was reduced by 30% (p=0.024, statistically significant) with AllerT 50 μg and by 19% (p=0.190, not statistically significant) with AllerT 100 μg. Both AllerT doses were associated with similar statistically significant improvements in the total score of the Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) and in the rhinoconjunctivitis symptom score throughout the birch pollen season. All other secondary endpoints showed similar efficacy trends.
AllerT was safe and well-tolerated throughout the two-month pre-seasonal treatment. Most adverse events were mild or moderate, resolved within 24 hours, and there were no reports of anaphylactic shock or grade 3 allergic reactions within 30 minutes following any of the injections.
COP vaccines can be applied to a broad variety of allergy indications. Besides AllerT for the treatment of birch pollen allergies, Anergis´ COP allergy vaccine pipeline currently includes AllerR for ragweed pollen allergies and AllerDM for dust mite allergies.
Company News: Publication Demonstrates Superior Activity of ISA Pharmaceuticals´ SLP® Vaccines Compared to Whole Protein Vaccines
– Study published in European Journal of Immunology elucidates different, improved antigen presentation and T cell-inducing power of SLP® vaccines
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced the publication of a peer-reviewed paper in the European Journal of Immunology.[1] The article describes a previously unknown mechanism that explains the excellent efficacy of ISA’s Synthetic Long Peptide (SLP®) vaccines. The authors demonstrate that compared to whole protein antigens, SLP®s are processed much more rapidly and efficiently by dendritic cells (DCs), resulting in an increased antigen presentation to CD4+ and CD8+ T cells, and enhanced CD8+ T cell activation. The improved presentation relates to a distinct intracellular localization of SLP®s after uptake by DCs.
Cancer immune therapy requires the induction of potent CD4+ and CD8+ T cell responses to the malignant cells. This is accomplished by DCs, the major antigen-presenting cells of the immune system. So far it has been challenging to induce a sufficiently potent reaction by vaccinating with whole protein antigens. In a number of preclinical and clinical studies, ISA Pharmaceuticals has already observed improved efficacy of its SLP® vaccines as compared to whole protein vaccines.
To study the underlying mechanism, researchers used both mouse and human DCs. They found that after incubation with SLP® vaccines and subsequent uptake by the DCs, the SLP®s are located in the cell, but are largely outside the cells’ endosomes. In contrast, protein antigens are processed inside endosomes, resulting in a much slower and different processing route. In the study, SLP®s were processed far more efficiently and distinctly into both MHC class I and II antigen presentation pathways than whole protein antigens. This lead to a strong activation of both CD4+ and CD8+ T cells, resulting in potent and efficient immune responses to the antigen.
In previously published clinical studies, ISA had already demonstrated the superiority of SLP® vaccines over short peptide vaccines. Short peptide vaccines, which fit precisely into MHC class I molecules, often do not result in a sufficiently long antigen presentation, and also carry the risk of inducing a mix of favorable pro-immunogenic and detrimental tolerogenic signals. Moreover, short peptide vaccines do not instate efficient immunologic memory. ISA also demonstrated that these differences are caused by the highly selective uptake, processing and presentation of SLP®s by professional antigen-presenting cells, and by the presence of both CD4 and CD8 epitopes in the long peptides.
[1] Rosalia et al.; “Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation”, DOI: 10.1002/eji.201343324
http://onlinelibrary.wiley.com/doi/10.1002/eji.201343324/abstract;jsessionid=F0FBA5A73F264503207C22EDF313FAB0.d04t03.
Company News: Curetis to Present Clinical Unyvero™ Data at Major Scientific Conferences
– Lower Respiratory Tract application: initial clinical evaluation data from U.S. center will be presented at ICAAC 2013 (USA)
– New application Implant and Tissue Infections: first data will be presented at DGHM/DGI meeting (Germany)
Curetis AG today announced the upcoming presentation of new clinical data on two Unyvero™ applications at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) in Denver, CO (Sept. 10-13) and at the 65th Joint Annual Meeting of the German Society for Hygiene and Microbiology and the German Society for Infectious Diseases (DGHM/DGI 2013) in Rostock, Germany (Sept. 22-25).
Curetis will introduce clinical data from a U.S. pre-FDA trial phase of its Unyvero™ LRT (Lower Respiratory Tract) infection application at the ICAAC conference. The poster ‘Evaluation of a Molecular Multiplex Test For Detection of Respiratory Microorganism and Antibiotic Resistance Genes in Clinical Specimens’[1] will present data generated at Northwestern Memorial Hospital (Chicago, IL) during the initial familiarization and training phase for the FDA trial. The FDA trial is now being conducted at four sites; all clinical data are blinded until completion of this ongoing trial which is expected for 2014. The LRT application is already marketed and branded outside the U.S. as the Unyvero™ P50 pneumonia application. During ICAAC, Curetis will also showcase its Unyvero™ Solution at booth no. 822 in the exhibition hall.
Moreover, Curetis will present data of its novel Unyvero™ i60 ITI application for the diagnosis of implant and tissue infections detecting pathogens and resistance markers at the annual DGHM/DGI meeting. The poster presentation ‘A new Multiplex PCR-Panel for the Detection of Pathogens Related to Implant and Tissue Infection’[2] will introduce the panel chosen for the diagnosis of eight indication areas and present initial validation and verification data with clinical samples. Curetis will also host the industry symposium ‘Implant and Tissue Infections – A Diagnostic Challenge’ (Sept. 24, 12:15-1:15pm, Auditorium 2) featuring talks and case studies by Prof. Petra Gastmeier (Berlin, Germany), Dr. Anne Thews (Holzgerlingen, Germany), Prof. Andrej Trampuz (Berlin, Germany), and Dr. Olivier Borens (Lausanne, Switzerland). A second poster based on data independently generated at the University Hospital in Basel, Switzerland will present a ‘Comparison of the Unyvero™ Pneumonia P50 Assay with standard culture and antimicrobial susceptibility testing’.[3]
[1] Presentation D-1655a, Session: #214 – Diagnosis and Epidemiology of Respiratory Infections, Sept. 13, 8:30-10:30am, Exhibit Hall A.
[2] Presentation DVP02, Postersession I (StAG Diagnostic Microbiology and Microbiology Procedures Quality Standards), Sept. 23, 3:00pm, Auditorium 1
[3] Presentation KMP14, Postersession II (StAG Clinical Microbiology and Infectious Diseases), Sept. 24, 3:00pm, Room HS323.
Company News: Three Peer-Reviewed Papers by ISA Pharmaceuticals Introduce Strategies to Improve Immunotherapy Against Cancer
– Local Delivery of Checkpoint Control Antibodies Greatly Improve Efficacy and Safety
– Promising Potential for Combinatorial Strategies
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced the publication of three peer-reviewed papers that demonstrate the benefit of local delivery of a checkpoint control antibody targeting CTLA-4 (cytotoxic T lymphocyte antigen-4) for the successful eradication of cancer and the reduction of side effects. The papers include a review that underlines the importance of strategies for combinatorial treatments to improve further the immunotherapy of cancer. ISA Pharmaceuticals is developing cancer immunotherapies along those lines, in particular its Synthetic Long Peptide (SLP®) vaccine ISA101 for the treatment of HPV-induced diseases, such as cervical cancer and head and neck cancer, and ISA203 for the treatment of various tumors including lung cancer, head and neck cancer, breast cancer and melanoma.
In a paper just published in Clinical Cancer Research [1], a team of scientists from Leiden University Medical Center (LUMC) and ISA Pharmaceuticals report that in preclinical mouse models of cancer, the injection of a CTLA-4 blocking antibody in a slow-release formulation close to the tumor is very effective in activating a systemic anti-tumor (CD8+) T cell response. CTLA-4 is a crucial immune checkpoint protein that down-regulates the body’s immune response. The low-dose local treatment (50μg subcutaneously in a slow-release vehicle) eradicates tumors, including distant tumors, as effectively as a high-dose systemic treatment (2×200μg intraperitoneally). The method also leads to a 1000-fold decrease of antibody levels in the serum, thereby reducing adverse events and the risk of autoimmunity.
These findings are supported by an increasing number of studies demonstrating that local targets, mainly present in the microenvironment of tumors and draining lymph nodes, are key players in tumor progression. As published in a second paper by researchers from LUMC and ISA, a review in the International Journal of Cancer [2], local immunotherapies have clear advantages over systemic treatments, both in their ability to shift tumor-promoting mechanisms towards effective tumor-eradicating immunity and in terms of reducing the risks of systemic administration.
In the third publication in Seminars in Immunology [3], current cancer immunotherapy approaches are reviewed, concluding that most standalone immunotherapeutic strategies either fail to affect progressive diseases and survival significantly – or only do so in a minority of patients. The authors support combinations of synthetic vaccines that stimulate tumor-specific T cell responses and adjuvants, immune-modulating antibodies, cytokines, or chemotherapy.
[1] Fransen MF et al. (2103), Clin Cancer Res, Published Online First June 20, 2013; doi: 10.1158/1078-0432.CCR-12-0781
[2] Fransen MF et al. (2013), Int. J. Cancer, 132: 1971–1976; doi: 10.1002/ijc.27755
[3] Arens R et al., (2013), Sem Immunol, Published Online First May 21, 2013;
doi: 10.1016/j.bbr.2011.03.031