Sanaria Inc. is the world’s only biotechnology company exclusively dedicated to the development and production of a malaria vaccine. It is also a participant in the 2007-08 NIH-CAP, a program funded by the National Institutes of Health and managed by Larta Institute. Based in Rockville, MD, Sanaria unveiled a brand new state-of-the-art clinical manufacturing facility in Oct. 2007.

VOX engaged in a Q&A with David Dolberg, Sanaria’s Director of Intellectual Property, to discuss the company’s short term goals and long term vision, the unique challenges Sanaria faces, and how it plans to overcome these challenges to successfully bring the malaria vaccine to market.

Q: Developing a successful malaria vaccine obviously has a social mission component. How can it be attractive to investors as a for-profit commodity? Would its success depend on whether Sanaria can reconcile a non-profit goal with a commercial objective?

A:   Since Sanaria’s PfSPZ vaccine will at once protect poor and rich alike, with equal efficacy, there should be no fundamental conflict, but it’s important that the allocation of both resources and returns is transparent and understood in advance by our investors. Sanaria’s business model targets two principal market segments - a global health market comprising donor agencies, foundations, and governments, and a high return market comprising business travelers, tourists, and governments (including the military) from industrialized nations. We estimate the total annual market potential to be at least $3 billion.

Q:  Sanaria is developing a vaccine for P. falciparum, one of several Plasmodium species protozoan parasites that cause malaria. Would the vaccine offer protection against other species of Plasmodium as well? If so, to what degree?

A: P. falciparum causes the deadliest form of malaria – resulting in a human death toll of more than 1 million individuals per year. P. falciparum is responsible for more than 98% of all deaths from malaria. Clinical studies have demonstrated that the immunogen on which Sanaria’s vaccine is based can induce protection against multiple strains of P. falciparum. Thus, Sanaria’s vaccine is expected to protect against all strains of P. falciparum, regardless of their geographic origin, but this will have to be proven in clinical trials. The second most important malaria-causing Plasmodium parasite is P. vivax. Malaria caused by P. vivax causes minimal mortality, but significant numbers of clinical cases. Based on the results of animal studies we anticipate that Sanaria’s P. falciparum vaccine will provide some cross-protection against P. vivax, however this too must be proven in clinical trials.

Q:  P. falciparum has proven to evolve quickly and develop a high degree of drug-resistance, therefore becoming more deadly with each cycle of infection. Is this a challenge in the development of a malaria vaccine and how does Sanaria plan to overcome this challenge? Similarly, given the history of malaria vaccines in general, what difficulties have Sanaria faced in the company’s history?

A:   The rapid evolution of drug resistance of P. falciparum is an enormous problem, and is generally due to a change (mutation) in the genetic code of a small area of one of the 5300 genes in the P. falciparum genome. This may prove to be a problem for recombinant subunit malaria vaccines that rely on immunity against one or a few proteins. The protective immunity afforded by Sanaria’s attenuated PfSPZ whole parasite vaccine is likely to be directed against targets on many P. falciparum proteins. If this is the case, it will be difficult for the parasite to evolve resistance, because it would have to mutate at perhaps hundreds of sites, not just one or a few as is the case for drug resistance. Sanaria’s major challenge has been the creation of a manufacturing process capable of producing sufficient quantities of attenuated whole parasite PfSPZ vaccine meeting regulatory standards (e.g. FDA standards). This has now been accomplished.

Q: The production of Sanaria’s attenuated malaria parasite vaccine has succeeded in a small-scale controlled environment. Is the manufacturing process feasible for mass production?

A:   Sanaria recently dedicated a 23,000 sq. ft. facility that features a custom-built Clinical Manufacturing Facility meeting the FDA’s GMP standards. This facility is capable of manufacturing all of the vaccine necessary for Phase I and Phase II clinical trials. It is likely that manufacturing for pivotal Phase III studies and commercial launch of the vaccine will require an expanded facility. However, the current manufacturing process is fully scalable and feasible for mass production.

Q:  Should everything proceed according to schedule, when will this malaria vaccine become commercially available?

A:   We hope to begin Phase 1/2a trials next year. If trials proceed according to plan we anticipate licensure and commercial availability in 5 to 6 years.

Q:  What is the difference between Sanaria’s vaccine and GlaxoSmithKline’s RTS,S, the “other” malaria vaccine that’s actually further along in terms of human trials?

A:   There are two major differences between Sanaria’s PfSPZ vaccine and all other malaria vaccines in clinical development, including RTS,S. The first difference is that Sanaria’s vaccine is a live attenuated, whole organism (infectious agent) vaccine that is capable of inducing immunity against the entire parasite. There are 25 licensed vaccines in the U.S. Sixteen of the 25 are based on a whole infectious agent, and 12 of the 16 are live attenuated infectious agent vaccines. Of the 25 licensed vaccines, only two are subunit recombinant protein vaccines. In contrast to Sanaria’s live attenuated PfSPZ vaccine, all other malaria vaccines in development are subunit recombinant or synthetic vaccines targeting only one (e.g. RTS,S) or a few P. falciparum proteins.

      The second difference is that Sanaria’s PfSPZ vaccine is intended to protect a high percentage of recipients for extended periods of time from becoming infected with P. falciparum. This is because the immunogen, or business part of the PfSPZ vaccine, which is the radiation attenuated P. falciparum sporozoite, has been shown to protect > 90% of recipients against P. falciparum when delivered by the bite of infected mosquitoes. At their current stages of development, RTS,S and other malaria vaccines appear to delay the time until infection, thereby potentially reducing the overall incidence of clinical malaria. However, it does not appear that these vaccines will significantly prevent infection with P. falciparum.

Q:  How did you learn about the NIH-CAP and what prompted you to apply for the program?

A:   As an NIH Phase II SBIR recipient, we heard about the NIH-CAP program through NIH. Although support from not-for-profits and governments will be sufficient to begin clinical trials, we anticipate that equity funding will be required to cover the expense of moving PfSPZ to licensure. Developing an effective malaria vaccine as a commercial product creates unique challenges of perception in the investment community, some of which result from the diversity of the market segments. The NIH-CAP program offers us the opportunity to develop a strategy and the presentation tools for tackling these challenges.

Q:  Sanaria has some prominent advisors on board, including Jeffery Sachs, the noted economist at Columbia University, and the backing of the Bill & Melinda Gates Foundation. With that in mind, in your opinion, what opportunities does the NIH-CAP offer that are not available from other resources? What do you hope to achieve after the conclusion of the program in 2008?

A:   Sanaria has attracted distinguished advisors and support because of devastating burden of malaria and the opportunity that Sanaria has created to address it. However, this may not be enough. Humanitarian value must be matched by investment value and this requires the development of a business strategy that takes advantage of support from both sectors, while addressing the needs of all market segments. In a sense, we are entering a business territory which is uncharted, and NIH-CAP and the Larta Institute offer a broad palette of advisors and advice. By the end of this program, we hope to have developed a strategy for financing this vaccine from trials to market.   

Q:  The recent news of Merck’s failed HIV vaccine is an example of the unpredictability and risks in vaccine development. It has also increased scrutiny of how vaccines are developed and tested in clinical trials. Has Merck’s failure and its aftermath affected Sanaria’s approach to the malaria vaccine? How do you plan to respond?

A:   Merck’s vaccine was a recombinant adenovirus expressing HIV proteins. This is another example of a subunit, recombinant approach. There are only two successful recombinant subunit vaccines, a hepatitis B vaccine and a human papilloma virus (HPV) vaccine, both pioneered by Merck. Both are recombinant protein vaccines. The experimental HIV vaccine was a recombinant virus vaccine, an experimental vaccine for which there is no example on the market. Sanaria’s vaccine is a live attenuated, whole infectious agent vaccine, a type of vaccine for which there is significantly more experience in humans. Because the vaccines are so different, the failure of the Merck vaccine does not affect the development of Sanaria’s malaria vaccine; however, any time a high profile vaccine or therapeutic fails it focuses more attention on the entire industry. The failure of the HIV vaccine has not affected Sanaria’s plans for developing the PfSPZ vaccine. However, it does re-emphasize the importance of the meticulous attention to quality, planning and execution that has allowed us to move forward so quickly, and will absolutely be required if we are to meet our future timelines.

If you would like to learn more about Sanaria, please visit http://www.sanaria.com/.