SBIR-STTR Award

The specific AIM of this Phase I SBIR proposal from Vical Incorporated is to move forward an immunotherapeutic vaccine for cytomegalovirus (CMV) from preclinical to clinical development. Vical has undertaken a program that focuses on the prevention of CMV viremia, disease, and associated complications in patients undergoing either hematopoietic or solid organ transplantation. The vaccine is a bivalent construct that encodes modified genes for the proteins gB and pp65, and is formulated in the poloxamer CRL 1005 in order to enhance B and T cell responses. This SBIR proposal will support that development through the final phases of pre-clinical safety studies, assay development, manufacturing, and planning for a Phase I clinical trial in humans. The specific milestone to be reached for moving to Phase II of the SBIR program will be to have the IND allowed in preparation to enroll the first patient by the end of 2003. The work plan takes the development process from the point of this project in March 03 forward to the IND allowance, estimated to occur on approximately 10/30/03. The specific goals to be achieved during that time, and financed in part by this Phase I SBIR application, include 1) the conduct of the pre-clinical safety and toxicology studies, 2) clinical protocol and site development, 3) the manufacture of GMP products, 4) the preclinical analytic testing plan and assay development, and 5) development of the clinical immunogenicity assays needed to support the clinical trials.

Thesaurus Terms:
cytomegalovirus, vaccine development, vector vaccine, viral vaccine experimental design, vaccine evaluation clinical research, human subject, immunologic assay /test, laboratory mouse, laboratory rat, plasmid

Vical Inc. of San Diego, Ca. is the largest GMP manufacturer of plasmid DNA for vaccine clinical trials in the world. We have manufactured GMP plasmid DNA vaccines that are being used or entering clinical trials for HIV (in the US and China), malaria (up to 9 plasmids), Ebola, WNV, and SARS. Vical has undertaken an internal Product Development Program that focuses on the control of CMV viremia and the reduction of CMV disease and associated complications in patients undergoing either hematopoietic cell (HCT) or solid organ transplantation (SOT). A Phase 1 SBIR (R43 AI058386) approved from Feb to July 2004 (originally planned for November 2003 to April 2004) supplied funds to assist us to develop a CMV DNA vaccine and prepare for IND filing. The final milestone for seeking a Phase II SBIR was IND allowance of the vaccine. That milestone was achieved in March 2004. The Phase II SBIR proposal will support that development of the Vical CMV immunotherapeutic vaccine through Phase 1 and Phase 2 trials over the next 3 years of development. Specifically, we plan to: 1) To move the Vical bivalent CMV vaccine with gB and pp65 genes (VCL-CB01) into Phase 1 clinical trials for evaluation of safety and immunogenicity. 2) To study VCL-CB01 in Phase 2 trials in the HCT population to determine potential endpoints for an efficacy trial 3) To develop a second generation trivalent CMV vaccine (VCL-CT01) encoding the gB, pp65, and IE1 genes 4) To advance either VCL-CB01 or VCL-CT01 in the SOT population in conjunction with the Collaborative Antiviral Study Group of the NIH