IAmA Stephen L. Hoffman the CEO of Sanaria Inc. Yesterday we reported in Science magazine that our malaria vaccine completely protected volunteers against malaria! AMA!

Thank you. Also, please extended this thanks to everyone who worked on the project.

Thanks. I will.

Are you gonna sell it cheaply to the poor or keep the prices up for profit?

We intend to use the vaccine initially in two markets. The first, and most important, is in mass administration campaigns to eliminate Plasmodium falciparum malaria in geographically defined areas in Africa and other parts of the world with endemic malaria. This will involve immunizing almost the entire population. For these campaigns the vaccine will be provided at low cost. The second market for the vaccine will be in non-immune individuals (e.g. traveler and military market) who travel from areas without malaria to areas with malaria in order to prevent malaria. The price of the vaccine will be higher for these individuals.

I don't understand why this isn't getting more attention, you are doing something fantastic here man! People will remember your efforts as heroic in the future and i do so today, kudos to you sir!

Thank you very much. We are very encouraged by our results so far and are certainly very happy with the attention that our publication has received; we have had feedback on this paper from all over the world. However, there is still much work to do and our efforts must continue for some time to come before we reach the target of licensing, commercializing and deploying an effective malaria vaccine.

Thank you all for your comments, questions, and support. I will return to this page in the near future to catch up on any new questions. Steve

how long has it taken you to make this vaccine?

The vaccine was an idea when we moved into our first 800 square foot facility using $550,000 of funds from an NIAID, NIH Small Business Innovation Research grant, exactly 10 years ago.

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Thus far, the project has cost more than $100M. The funds have come from many sources. The most funds have come from competitive grants and support of the clinical trial by the National Institute of Allergy and Infectious Disease (NIAID), NIH. However, the PATH-Malaria Vaccine Initiative (MVI) using funds from the Bill and Melinda Gates Foundation has also provided substantial funding. Additional support has come from the Military Infectious Disease Program, the Naval Medical Research Center, TI-Pharma (a Dutch non profit), European Vaccine Initiative, Marathon Oil, The Tanzanian Commission on Science and Technology, the Ifakara Health Institute (Tanzania), the Swiss TPH, German Centre for Infection Research and University of Tubingen, Oxford University, Barcelona Centre for International Health Research, Wellcome Trust, Institute for OneWorld Health with funds from the Gates Foundation, the State of Maryland, and others.

Our primary return on our investment will be to eliminate Plasmodium falciparum malaria. However, in selling the vaccine to travelers, we do anticipate a significant profit.

What's the next step, do you plan on bringing this to Africa / areas most affected?

The next clinical trial of the PfSPZ Vaccine will begin at the Ifakara Health Institute (IHI) in Bagamoyo, Tanzania in the next few months. This trial is being funded by the Tanzanian Commission on Science and Technology, the IHI, and the Swiss Tropical Public Health Institute (Swiss TPH). This will be followed by trials beginning this year and early next year at the University of Bamako, Mali (funded by the Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH) and in Equatorial Guinea (funded by the Equatorial Guinea Government and Marathon Oil). We anticipate trials in Kenya, Burkina Faso, Gabon, and Mozambique to follow shortly thereafter. As described above, we are committed to developing and deploying a vaccine for use in mass administration campaigns to eliminate malaria in Africa and endemic areas.

I only glanced through the paper in Science, so sorry if these questions were addressed there. What sort of side-effects are associated with getting the same antigen administered 6 times? Is the timing of administration important?

As described in great detail in the paper, especially in the Supplementary Materials that are online, the vaccine was well tolerated and safe. There were minor adverse events, and they did not increase with increasing numbers of doses of vaccine or an increase in the numbers of PfSPZ (the weakened malaria parasite) per dose of vaccine. We will of course have to establish safety in thousands of individuals before licensing the vaccine.

We think that the timing of administration will be very important, and the next set of clinical trials are being designed to address this question, and to optimize the immunization regimen with the least number of doses during the shortest period of time.

Heard about this on NPR yesterday, awesome news!

I heard a bit of this yesterday, but wanted more detail. Can you comment on why malaria in particular is a difficult disease to create a vaccine for? I mean more so than things we already have vaccines for like Polio, Measles, etc.

We have vaccines against viruses (e.g. polio, measles) and bacteria (e.g. typhoid fever). However, we do not have licensed human vaccines against parasites like those that cause malaria. Malaria parasites are much more complex than viruses and bacteria. Malaria parasites have very biologically distinct stages in the human – in the liver and bloodstream – and in the mosquito, each of which is different in terms of the cellular structures and proteins present. Consequently, a malaria vaccine is needed that addresses that complexity. Vaccine candidates that target only one out of the thousands of proteins in the parasites do not do this. The PfSPZ Vaccine is composed of whole parasites that contain many of the malaria proteins, thereby addressing directly the issue of complexity.

Steve, you spoke to my intro to global health class when I was a freshman in college about six years ago. Your story was one of many from that class that got me interested in global health and inspired me to hopefully pursue it as a career. I believe you said you have probably subjected yourself to thousands if not millions of mosquito bites as a part of this research. Glad they weren't in vein! (pun very intended)

Glad to hear you have made so much progress with the vaccine!

My questions:

• What are you future plans for dealing with the IP and costing of the drug as you move forward to a hopefully very successful rollout? Obviously there are potentially competing interests for something like this in terms of access vs profit. Do you take any lessons from the HIV/AIDS epidemic, TB epidemic or the various neglected diseases in designing how you hope people will access this vaccine?

• I imagine you might be able to get some sort of expedited review for this as the FDA has recently been keen on speeding on the process on certain breakthrough medications such as this. If you can get the USG to buy into this we could see some significant coverage rather quickly. What are your plans on the regulatory front?

• Also as a small, independent company, does that offer you and leeway that the large pharmaceutical and biotech companies do not offer or is it more of a hinderance? Do you believe this research will suffice for a phase I trial of the vaccine?

• Are there any worries about resistance with your mechanism of action?

Thanks!

Edit: Expanded on my Qs! So many Qs!

Thanks. I am glad to hear that you are still intensely interested in global health, and proud that I may have played a small part in the development of your interest.

We hold all the IP on PfSPZ (the vaccine), so we have complete freedom to operate in regard to the roll out of the vaccine. As described above, our goal is provide vaccine for mass administration campaigns at low cost, and to use some of the profits from selling vaccine in the travelers's market to facilitate low cost delivery for mass administration campaigns in endemic areas. Our collaborators around the world are experts in the implementation of programs to control HIV, TB, malaria, and neglected diseases. We will continue to expand working with these and other collaborators in order to most efficiently implement immmunization programs.

We have worked closely with the FDA and regulatory authorities in Europe and Africa and will continue to do so to expedite the regulatory processes.

Because our entire focus is on development and implementation of whole sporozoite vaccines to eliminate malaria, we are able to focus our efforts in a way that other biotech companies and most pharmaceutical companies cannot, because they generally have balanced portfolios with multiple products. This is of course risky for us, but has allowed us to move expeditiously and at lower cost than is generally thought to be required to fully develop, license and commercialize a vaccine. We are now planning the path by which we move from phase 1 to phase 2 to phase 3.

Since our vaccine is a whole organism vaccine, which has more than 5,000 genes, we think the immunity is directed against 10s to 100s of target proteins, and that different individuals are protected by immune responses against multiple different proteins. If this is the case, it will be difficult for the parasite to develop resistance to our vaccine. However, in phase 4 (after licensure), this will have to be carefully investigated.

How much is Bill Gates' involvement in this?

In 2006 we received a $29.3M grant from the PATH Malaria Vaccine Initiative with funds from the Bill and Melinda Gates Foundation (BMGF) to support our efforts. These funds enabled us to build our Clinical Manufacturing Facility, manufacture the vaccine, and conduct the first clinical trial of the PfSPZ Vaccine conducted in 2009-2010. The BMGF was not involved in the trial conducted at the Vaccine Research Center, NIAID, NIH, the results of which were reported in Science yesterday. We anticipate a productive working relationship with the BMGF in the future to help bring our vaccine through to licensure and deployment for mass administration campaigns to eliminate malaria.

Hello Mr. Hoffman-

I have a few questions, based off of the short article you posted in Scientific American.

• How long does the overall injection process take? The article stated that 5 separate injections were necessary, but is that over the course of several hours, days, weeks?

• In terms of getting its availability to the field, have you had any NGOs, health organizations, etc. contact you about getting the vaccine into greater production and then transporting it to the areas that most need it? Where do you anticipate the greatest hurdles will be in making this available in Africa/S Asia/SE Asia?

• Finally, just as a more personal question, it seems like there was a lot of doubt surrounding the vaccine's viability before your latest tests. Did you ever feel like you were fighting an unwinnable battle? Any pearls of wisdom that helped you get through harder times?

In this trial we gave four injections at 4 week intervals and the fifth injection 8 weeks later. We are now working to see if we can reduce the numbers of injections and the overall time for immunization.

We are working with many groups to identify and overcome challenges to implementation of the vaccine, and anticipate the number of organizations will increase over the next few years. In one country we are working with the Ministry of Health, an oil company, an NGO, and physician scientists from all over Africa, Europe and the U.S. to study and optimize implementation.

I never thought it was unwinnable. We can discuss the pearls of wisdom over a drink sometime. Much of what I have gone through is summarized in the book by Bill Shore, "The Imaginations of Unreasonable Men," published in 2010.

How long do you think it will be before this will be viable to use on a large scale? Any idea how many booster shots would be required for someone living in a malarial area, or is it too early to tell?

Finally, what is the business case for a vaccine like this, given that the people that most need it tend to be among the poorest in the world? Selling it to NGOs? US foreign aid?

As stated in other answers, if all goes as planned, we hope to have the vaccine licensed in 3.5 to 5 years. Initially we would be using it for mass administration campaigns in populations of several hundred thousand individuals. Further scale up will be dependent on the results and expanding manufacturing capacity. This is part of our strategic plan.

We are working to minimize the numbers of injections, but there is no way to predict how many until we have completed the planned clinical trials.

We anticipate that the vaccine will be bought and distributed by international agencies such as UNICEF and the Global Fund, USAID and other national aid agencies, NGOs and foundation, and by the governments of some of the countries.

Will this vaccine protect against P vivax and P ovale?

We do not know the answer to this question yet. However, data from rodent model malarias, suggest that there will be cross protection. Thus, our hope is that Sanaria PfSPZ Vaccine will protect not only against P. falciparum, but also against other species of human malaria parasites, including P. vivax, P. malariae, P. ovale, and P. knowlesi. This cross protection may be dependent on dose of vaccine administered, but we think that the complexity of our vaccine will work to our advantage for cross protection. We will be able to address this question better when we conduct clinical trials in locations where these other species of malaria parasite are found. However, since P. falciparum is responsible for more than 98% of all deaths from malaria, we would be quite happy if we just achieve elimination of these deaths. By the way, we are working in parallel to develop P. vivax and P. knowlesi SPZ vaccines that can be used in the event we need them.

How many hours sleep do you get at night?

Not enough!!!

What prompted your work in this field? What made you want to work on the vaccine for this condition?

Thank you for this huge accomplishment.

Thank you for your kind comment. I am a tropical infectious disease specialist and malaria is the most important tropical infectious disease. Thus, it was natural for me to work on malaria. Prior to working on vaccine development, I worked in the field on diagnosis, treatment, chemoprophylaxis, epidemiology, and immunology of malaria and other tropical infectious diseases. I was quite successful in developing therapies to reduce mortality of diseases like typhoid fever, but was unsuccessful in improving treatment of cerebral malaria. I decided that the best way to make an impact was to develop a vaccine. It has taken longer than I expected!!

I noticed your study used Anopheles stephensi mosquitoes. Is this because they're easier to care for than Anopheles gambiae?

Yes

Malaria largely affects impoverished areas. Since Sanaria is a for-profit company how do you approach the market ethically so that your drug may help as many people as possible while growing as a company?

As a product engineer working with medical devices, I am always interested in this area. African markets are largely under-serviced both with pharmaceuticals and medical devices. I like to see how people plan to address health concerns there in a way that makes business sense.

Thanks for the question. It is answered in a number of my other responses. If that is not adequate, please let me know.

How do you make the sporozoite vaccine?

We grow malaria parasites and mosquitoes in culture, feed the parasites to the mosquitoes, allow the parasites to develop in the mosquitoes, irradiate the parasite-infected mosquitoes, extract the sporozoites from the mosquitoes, purify the sporozoites, vial the sporozoites, and freeze. All of this is done under aseptic conditions and in compliance with FDA standards.

You guys did a brilliant job, you are going to save hundreds of thousands of peoples lives. How long have you been working with this vaccine ? Edit: Forgot a word

Thanks. 10 years, see above.

Dr Hoffman, in your photograph you look so youthful yet a quick internet search reveals you are over 60 years of age. How can this be??? What is your work out regime/diet program?

Since we need to provide the vaccine at low cost for mass administration campaigns, I am writing a book on my work out regimen and diet to raise funds. You will have to wait for the book.

P.S. Many Sanarians, including me, work out together after work on Tuesday, Wednesday, and Thursday evenings following "Insanity" and "P-90X."

"Far better is it to dare mighty things, to win glorious triumphs, even though checkered by failure... than to rank with those poor spirits who neither enjoy nor suffer much, because they live in a gray twilight that knows not victory nor defeat."

~Theodore Roosevelt

Congrats to you and your amazing team at Sanaria Inc. for a job well done!!

Thanks.

I read an article on this but I'm afraid that I skimmed a [more than a little] bit. Can you briefly synopsize what break-through allowed this vaccine to succeed?

In 2011 we published a paper in Science magazine on a previous trial of the PfSPZ Vaccine. The last sentence of the abstract was the following: "Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria." In this trial we administered the vaccine by intravenous injection, and as predicted we protected all the individuals who received the highest dosage of vaccine. In order to get to the point of initiating any trial, we had to develop a manufacturing process that allowed us to make the aseptic, purified, cryopreserved, attenuated PfSPZ of which the vaccine is composed.

I have always been interested in DoD involvement in science.

Do you think that Walter Reed and DoD involvement assisted with the development of the vaccine?

Disclaimer. I served in the U.S. Navy Medical Corps for 21 years. Thus, I am very positive about the military's contribution. Our work is based on studies that were first done in the early 1970s and then repeated in the 1990s in which subjects were immunized by the bite of P. falciparum sporozoite-infected mosquitoes and shown to be protected. The studies in 1970s and the 1990s were funded by the Naval Medical Research and Development Command and the Military Infectious Disease Research Program (MIDRP) with significant involvement of the Naval Medical Research Institute/Center (NMRC) and the Walter Reed Army Institute of Research (WRAIR). NMRC has been a close collaborator of Sanaria's since our inception, and WRAIR has been collaborating with us for four years. In 2005 we received a critically important $4.1M grant from MIDRP to support our efforts. The first author on our first Science publication was CAPT Epstein from NMRC. Thus, the DoD has played a fundamental, critical role in development of this vaccine approach and we are planning a close partnership to take us over the finish line to licensure of a vaccine to prevent malaria in our troops.

Hi Stephen. I am a microbiologist who develops treatments for tropical diseases.

Looking through the paper, I saw 2 major issues with this vaccine:

1. Patients were vaccinated with cryopreserved plasmodium, up to 6 times over the course of several months. How do you plan on dealing with delivery issues relating to cold storage in Africa and other developing regions? Also, vaccine compliance might be weak, as several doses are required to induce protective immunity. How do you plan on immunizing thousands of people in outlying areas with several doses per person?

2. There seemed to be an unusually large number of adverse events associated with this vaccine. Of 57 vaccinees, there were many mild AEs, and there was a severe AE. Do you really think this will gain approval in the age of the litigation attorney?

I fully support what you are trying to do, but feel that this paper is receiving an undue amount of press for a not particularly promising vaccine.

1. In the trial reported on in Science yesterday, the six volunteers who received 5 doses of vaccine were completely protected against malaria. The next studies are being designed to optimize the immunization regimen and to hopefully reduce the numbers of doses.

The vaccine is stored and transported in the vapor phase of liquid nitrogen (LNVP). Our team, which includes colleagues in Africa, Europe, and the U.S. believes that storage and transport in LNVP has major advantages over the current cold chain, because it is independent of electricity. Dr. Eric James, our head of Vaccine Stabilization and Logistics, in collaboration with colleagues in the U.S., Tanzania, and Switzerland has recently published an article on this subject (CR Garcia et al., Vaccine, 2013).

In collaboration with health care workers, social scientists, vaccinologists, logisticians, and bio-engineers we will be working during the next 4 years to optimize our approach to vaccine mass administration campaigns to optimize compliance and vaccine coverage.

1. The serious adverse event you referred to was not caused by the vaccine.

From our perspective there were not an unusually large number of adverse events. Furthermore, most of the adverse events were mild. The trial reported on in Science yesterday was not a double blind placebo controlled trial. As we move towards licensure, the clinical trials will be double blind and placebo-controlled. We expect that in such trials most of the adverse events reported on in this study will turn out to occur at the same rate in the placebo group; they will not be associated with the vaccine. We approach conduct and reporting of clinical trials with discipline and rigor and in compliance with all regulatory standards. We are confident that with this approach we will achieve licensure and deployment of the vaccine.

1. Thank you for your support. We are thankful that our colleagues all over the world think that our vaccine is very promising.

This seems like a fairly aggressive vaccine agenda. How long do you suppose approval will take? Also, what does this mean for other researchers in the malaria field, such as those working in vector control?

Thanks for the questions.

If all goes as we have planned, we think we can achieve approval in 3.5 to 5 years.

They should keep working! We have many challenges to face, and malaria is a formidable foe. We think that a highly effective vaccine that prevents infection, disease and transmission will be our most important tool for focused elimination campaigns and eventual eradication, but we need all the tools we can muster to fight this disease.

Can you describe the feeling of knowing that your (and your team's) research will save countless lives?

If were a poet instead of a physician scientist I would be better able to answer your wonderful question. Our team, myself included, at Sanaria feels blessed to be able to go to work every day knowing that if we succeed, "countless lives" will be saved. This is a treasure to us. When we received the positive results, we were all overcome with joy and gratitude. However, we are also mindful of the fact that we have many more challenges to face before we can conclude that we have saved any lives.