Immunostimulation with the MelVac platform emulates the most optimal, systemic, natural immune response. Further, it encompasses the most current knowledge of cancer immunology. The CureVax product DC-MelVac and its platform technology was patented in 2006 and that consists of several major components, each of which has entirely novel functions. The unique components of the CureVax vaccine platform are:

A. Vaccinia Virus with cytokine production. We chose IL-2 as it is the most appropriate T cell driving cytokine. The way our clinical protocol is designed is that it is expected to drive the activation of T cells previously rendered anergic by the cancer. This is most efficiently accomplished and driven by recombinant vaccinia-IL-2. Activation of anergic T cells by this mechanism is novel both as a concept and by its use as a parameter of clinical efficacy. This is an innovative approach that has not been previously attempted. We believe without this step, optimal, multivalent cancer associated T cell response is not possible, nor sustainable.

B. The second novelty of our patent/platform technology is the generation of a multivalent antigen repertoire capable of activating multiple cytotoxic T cells simultaneously by an innovative “vaccinia based antigen retrieval” technique. This technology alleviates the deficiency of the use of single defined antigens and the use of additional adjuvants. To our knowledge, no technology or product exists that equals the multitude of tumor-associated antigens that we have in our allogeneic vaccine mix. Furthermore, the MelVac platform is accompanied with its own adjuvant (vaccinia virus) that can prime and stimulate the maturation of dendritic cells into supreme antigen-presenting cells. All failures of dendritic cell immunotherapy to date are because of the inability to allow them to mature optimally in vitro. For the first time, in a carefully dose titrated manner, we will allow the space for the dendritic cells to mature to perform their natural antigen presentation’ function. The present knowledge base allows us to select the most optimal dendritic cell subsets.

The beauty of the MelVac platform and its lead product, DC-MelVac, is that it is not complex science; we are just emulating the natural immune response and is based on our knowledge base of cutting edge cancer immunology and immunotherapy. Our patent is extremely innovative and it allows for the intuitive use of vaccinia virus, a concept which has never been attempted. We are emulating the success of vaccines in infectious disease and moving them into cancer immunotherapy.

We believe that, in part, these very concepts are responsible for the positive results for checkpoint inhibitors. Yet, approximately 50% patients on checkpoint inhibitors are not responsive, validating the concept that reactivation of anergic cancer-associated T cells is necessary. However, in the absence of positive stimulation that targets central memory and effector T cell populations against cancer, curative treatment regimens will remain to be a challenge.

This technology addresses both these concepts regarding re-activation of anergic T cells and reactivation of central memory pool of T cells.

Oncolysates work by simple and elegant antigen capture and presentation as in a natural infection. We have published and presented our data indicating that melanoma –associated antigens can be found on the surface of Oncolysate-Pulsed Dendritic Cells.

The CureVax MelVac oncolysate portion of the vaccine will be “off the shelf” – in a vial, which will be administered by trained personnel. The use of dendritic cells for the DC-MelVac vaccination will be laboratory (hospital/blood bank) based. It is worthwhile to note that our IP allows us to use only the MelVac oncolysate, which can certainly be administered in a physician’s office.

The MelVac platform patent allows CureVax to use vaccinia virus to drive the expression of any relevant cytokine or tumor antigen, individually or in combination.

Dr. Wallack has used DC-MelVac as “compassionate” treatment in three patients. The results from these treatments indicate that DC-MelVac induces an anti- melanoma immune response, as well as clinical responses.