Immunovaccine highlights cancer vaccine at AACR

Vaccine shows enhanced therapeutic potential when combined with cyclophosphamide and the checkpoint inhibitor anti-PD-1

Lloyd Dunlap
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HALIFAX, Nova Scotia—Immunovaccine Inc. a clinical-stage vaccine company, presented positive data from clinical and preclinical vaccine studies, including DPX-Survivac, the company’s lead therapeutic cancer vaccine, this weekend at the American Association for Cancer Research (AACR) 2014 Annual Meeting. In a poster presentation, Immunovaccine highlighted results demonstrating that metronomic cyclophosphamide (mCPA), an immune modulating agent, enhanced the immunogenicity of DepoVax™-based vaccines in preclinical cancer models consistent with previously reported Phase 1 data showing a similar enhancement of DPX-Survivac in patients. Importantly, the animal studies demonstrated the combination therapy’s ability to eliminate advanced tumors that could not be treated with vaccine or mCPA alone. Tumors exposed to the combination therapy specifically exhibited an increase in T cell activation markers, suggesting increased immune-mediated anti-tumor activity at the tumor site with the vaccine/mCPA therapy and further supporting the use of the combination therapy in clinical trials.
The addition of anti-PD-1 checkpoint inhibitor to the DepoVax vaccine/mCPA combination resulted in further enhanced anti-tumor activity, which allowed the treatment of more advanced tumors. The effective tumor regressions that were observed could not be achieved without the use of vaccine or the use of anti-PD-1.   
Checkpoint proteins are known to suppress immune activity and their expression was increased in tumors under immune attack from the vaccine therapy. Down-regulating suppressive mechanisms at the tumor level with the use of checkpoint inhibitors allowed the robust vaccine therapy to cause tumor regressions in animals, suggesting that the triple combination of vaccine, cyclophosphamide and anti-PD-1 may be well suited for the treatment of patients with aggressive tumors who may not otherwise respond to a less aggressive vaccine therapy.  
“These study results represent strong support for Immunovaccine’s belief that combination immunotherapies will be essential to treat cancer,” said Marc Mansour, chief operating officer of Immunovaccine.  “Combining a vaccine with immune modulators like cyclophosphamide may be most effective in patients with no evidence of disease and with a high rate of recurrence, while combining vaccine-based therapies with synergistic checkpoint inhibitors may be particularly useful for patients with more aggressive disease.”
A second poster presentation related to DPX-Survivac will also be made during the AACR conference by an Immunovaccine collaborator, Caprion’s ImmuneCarta business unit. This presentation, which will take place on Wednesday, April 9, will detail immune response results from Immunovaccine’s Phase 1 study of DPX-Survivac in ovarian cancer patients. Findings demonstrated that treatment with DPX-Survivac induced durable target T cell responses, with these responses more robust when DPX-Survivac was combined with cyclophosphamide as an immune modulator. These results are consistent with the preclinical study results presented at AACR and provide further support for the potential for combining DPX-Survivac with complementary immune modulators and immunotherapies. 
Immunovaccine expects a large randomized Phase 2 trial of DPX-Survivac to be initiated in 2014 in ovarian cancer. The 250-patient trial will be sponsored and conducted by Canada’s NCIC Clinical Trials Group. Additionally, researchers at the University of Rome will be initiating a Phase 1/2 trial of DPX-Survivac in glioblastoma (brain cancer) with the first patient receiving the vaccine in the first half of 2014.
Also at AACR, Immunovaccine announced that its DepoVax adjuvanting technology will underlie the design of a new cancer vaccine trial that will be conducted by the Dana-Farber Cancer Institute to treat cervical and head and neck cancer.
In a competitive process, Dana-Farber has been awarded a research grant of $1.2 million for clinical evaluation of its cancer vaccine. The 3-year grant from Stand Up To Cancer (SU2C) and the Farrah Fawcett Foundation will be used to fund a Phase 1 clinical trial of the group’s peptide cancer antigen formulated in DepoVax in patients with HPV-related cervical and head and neck cancers.
The grant was awarded based on a proposal highlighting the potential of Dana-Farber’s proposed cancer antigen identified by a new mass spectrometry method termed Poisson detection MS and Immunovaccine’s DepoVax platform. The DepoVax data focused on clinical trial results with DPX-Survivac, which demonstrated strong immune response activity in cancer patients and the immune enhancement observed with cyclophosphamide. Dana-Farber’s proposed Phase 1 study in HPV-related cancers will use the same approach, formulating the Institute's peptide-based vaccine in DepoVax and administering it to patients in combination with cyclophosphamide.
“We believe that the grant committee was encouraged by novel interdisciplinary science in conjunction with the powerful immunogenicity data that Immunovaccine has collected to date with our DPX-Survivac cancer vaccine candidate,” stated Immunovaccine’s Mansour. “We are excited to work with the talented team at Dana-Farber and add value to their clinical program with our DepoVax technology. Our previous work with DPX-Survivac gives us confidence that DepoVax has the potential to induce strong immunological responses to their novel antigen to enable the vaccine in the clinic.”
The SU2C-Farrah Fawcett Foundation HPV Translational Research Team Grant provides three years of funding for a multidisciplinary, translational cancer research project that addresses critical problems in HPV-related cancers and that can deliver near-term patient benefit through investigation by a team of two expert investigators. To be considered for the grant, research project designs were required to include clear plans indicating how the work will be translated into the clinic and deliver near-term benefits to patients with HPV-related cancers. HPV infection causes virtually all cervical cancers, and many anal, vaginal, vulvar, penile, and oropharyngeal cancers.
DepoVax is a patented formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system, resulting in a strong, specific and sustained immune response with the capability for single-dose effectiveness. The DepoVax platform possesses impressive flexibility, allowing it to work with a broad range of target antigens in various therapeutic applications. The technology is also commercially scalable, with potential for years of stability and ease of use in the clinic.
DPX-Survivac consists of survivin-based peptide antigens formulated in the DepoVax™ adjuvanting platform. Survivin has been recognized by the National Cancer Institute as a promising tumor-associated antigen (TAA) because of its therapeutic potential and its cancer specificity. Survivin is broadly over-expressed in solid tumors and blood cancers including ovarian, breast, colon and lung cancers, among others. Survivin plays an essential role in antagonizing apoptosis, supporting tumor-associated angiogenesis and promoting resistance to various anti-cancer therapies. Survivin is also a prognostic factor for many cancers and it is found in a high percentage of cancer patients.
The DPX-Survivac vaccine is thought to work by eliciting a cytotoxic T-cell immune response against cells presenting survivin peptides on HLA class I molecules. This targeted therapy attempts to use the immune system to actively search for tumor cells expressing survivin and destroy them.
Immunovaccine Inc. develops cancer immunotherapies and infectious disease vaccines based on the Company’s DepoVax platform, a patented formulation that provides controlled and prolonged exposure of antigens and adjuvants to the immune system. Immunovaccine has advanced two T-cell activation therapies for cancer through Phase 1 human clinical trials. Lead cancer vaccine therapy, DPX-Survivac, is expected to enter Phase 2 clinical studies in 2014 in ovarian cancer and glioblastoma. The Company is also advancing an infectious disease pipeline including innovative vaccines for respiratory syncytial virus (RSV) and anthrax.

Lloyd Dunlap

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