The ideal tool for eliminating Plasmodium falciparum (Pf), the causative agent of 99% of all malaria deaths, would be a highly effective vaccine that prevents blood stage infection and thereby prevents the disease and transmission. The only immunogens demonstrated able to induce > 90%, sustained (10-28 months) protective efficacy in humans are Pf sporozoites (SPZ). Sanaria's goal is to develop and commercialize a Pf SPZ vaccine that prevents Pf blood stage infection in > 90% of recipients. The SanariaTM PfSPZ Vaccine is composed of aseptic, attenuated, purified, cryopreserved PfSPZ. The platform technology developed to manufacture the PfSPZ Vaccine has facilitated manufacture of PfSPZ for infection of volunteers to test vaccines and drugs (PfSPZ Challenge) and for vaccination with PfSPZ Challenge under chloroquine protection (PfSPZ-CVac). In late November 2012 our collaborators at the Vaccine Research Center, NIAID, NIH, established that IV immunization with PfSPZ Vaccine protected 100% of volunteers against malaria. In 2011/2012 collaborators in the UK, US, and Germany demonstrated IM, ID, and IV administration of PfSPZ Challenge infected 100% of volunteers. In October 2012, the 1st clinical trial of PfSPZ-CVac began in the Netherlands. These 3 products are on an aggressive timeline to commercialization with 11 clinical trials in 8 countries on 3 continents planned for the next 15 months. When Sanaria was established, many considered it impossible to manufacture PfSPZ that would meet regulatory standards. When this was achieved under the first Phase II SBIR of this grant, it was argued that PfSPZ could not be manufactured to meet cost of goods standards. In the Competitive Renewal of that Phase II SBIR for which we report our Key Results herein, we made substantial progress toward reducing cost of goods by innovatively improving the efficiency of manufacturing and release assays. Based on that progress we have designed a manufacturing facility to be built within our current space that will conservatively manufacture 107 vials/year o 4.5x104 PfSPZ/vial at <$3/vial. We previously thought the new facility would have to be at a different site, cost $50M, and require 3 years to design, build and validate. Based on our innovations in manufacturing, success in the clinic, and the increased demand for our PfSPZ products, we re-designed the facility as an extension of our current Clinical Manufacturing Facility. It can be built at a cost of ~$10M and be operational in <1.5 years from initiation. In tis Competitive Renewal Proposal we will establish the innovations to allow full integration of the scaled up process steps for manufacture of PfSPZ products in the new facility. We will translate our innovations and advances into a robust process at a higher scale, including refining the equipment, tools, and processes at each step (1-18 months). Preliminary integration (months 18-30) will be followed by a finalized process in the new facility (months 30-36). This will furthe reduce cost of goods for all of Sanaria's PfSPZ-based products, and accelerate Phase 3 trials, licensure and commercialization by putting manufacturing on track with Sanaria's clinical development efforts.
Malaria causes 500 million clinical cases and nearly 1 million deaths annually, is responsible for >1% loss of GDP in Africa annually and is a serious concern for travelers and military personnel. Sanaria's goal is to develop and commercialize a >90% protective malaria vaccine for three primary markets with a potential for >$1 billion annual revenues. Travelers from the developed world to malaria endemic areas, military personnel, and geographically focused elimination campaigns are the initial markets. The eventual goal though continues to be infants and young children in the developing world and eventual eradication of the disease. Success in this Phase II SBIR renewal will leave Sanaria ideally placed to design and implement an enhanced manufacturing facility in which the company's malaria vaccine can be optimally manufactured for pivotal Phase 3 studies, licensure and commercial launch.
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