Malaria is a nasty disease resulting from an infection by the Plasmodium parasite that occurs via injection by an infected mosquito, and that, according the WHO, happened to about 200 million people in 2012 (WHO Malaria Facts). Fever and chills ensue and, if untreated, death, and this happened to about 600,000 people, mostly children in Africa, in 2012. While drug treatment exists and is being improved by newer drugs, combinations, and better distribution and measures like preventing bites with netting and killing mosquitoes and destroying their habitat are helping reduce mortality, a malaria vaccine has been a long-sought goal of the global health community. A vaccine is a major challenge though. The parasite goes through a number of stages in the human host and the insect vector (see a nice graphic at Malaria Vaccine Initiative) and how, when, and where the human immune system mounts a successful response are not known.
Vaccine developers have taken three vaccine approaches (also at Malaria Vaccine Initiative). The first is to aim at the early stage of an infection when the parasite is infecting the host liver; the most advanced vaccine, GlaxoSmithKline’s (GSK) RTS,S AS01 in Phase 3 clinical trials, is of this type. The second is to generate an immune response to the parasite while it is rapidly reproducing in the host red blood cells, reducing the severity of the disease and allowing time for the innate immune response to occur. The third, using a transmission-blocking vaccine (TBV), is my favorite because it targets the parasite while it is reproducing in the mosquito using antibodies obtained from the host. Essentially the vaccine turns a human into a system to deliver antibodies to treat the vector’s malaria. The idea for a TBV has been around at least since 1987 when studies confirmed that the blood of malaria sufferers contained antibodies that reduced the number of parasites in mosquitoes (e.g., Mendis et al. 1987 in which the researchers dissected out the mosquito gut to look for parasites), but it has only been in the last three years that candidates have advanced into clinical trials. The primary sponsors of the trials have been the Malaria Vaccine Initiate (MVI is run by the Seattle-based global health product developer, PATH, and funded by the Gates Foundation) and the NIH’s National Institute for Allergy and Infectious Diseases.
MVI’s lead TBV candidate was Psf25-EPA, so named because it consists of antigens to a Plasmodium surface protein and a detoxified version of an immune-stimulating bacterial protein. Unfortunately, it failed to generate a strong enough response in a Phase I trial in 2012 (MVI Call for Letters of Intent). While a number of companies and academic groups have expressed a variety of the parasite’s surface proteins in a range of expression systems (I noted one in yeast and another in algae), the Fraunhofer Center for Molecular Biotechnology (FCMB) evidently had the best proposal and was selected by MVI to fill the gap left by the failure of Psf25-EPA. Also apparently FCMB was able to move its candidate, Psf25-CP, into trials quickly. Recruiting for Phase I started last November (Clinicaltrials.gov entry), and the trial got under way this past month (FierceVaccines iBio press release, FierceVaccines iBio press release). Since I’m interested in how multiple parties collaborate to develop global health products, I looked into the background of this project and found not all the players on the same page.
The FCMB is part of the globe-spanning Fraunhofer Gesellschaft, a German-based research and development non-profit that has 67 institutes in Germany and offices and centers around the world including 11 in the US (Fraunhofer). The Fraunhofer has 23,000 employees and $2 billion plus budget, 30% from the government and 70% from government and industry contracts (Fraunhofer Wikipedia article). The FCMB is in Newark, DE, and has 90 employees focused on recombinant protein expression in a proprietary plant-based expression system (FCMB). It has a GMP-compliant pilot plant and projects for vaccines and antibodies for influenza, Trypanosomiasis (sleeping sickness), yellow fever, hookworm, HPV, and malaria, the last supported by a Gates grant of $9.85 million received in 2009 (FCMB press release).
As noted in the above-cited press release, apparently FCMB has a commercial partner in the development of the expression system and in the malaria TBV project, a company called iBio, Inc. iBio has a 2011-dated website (iBio Inc.), that seemed to be light on details, but since it is a public company listed on the NYSE, I looked at its SEC filings and analysts’ reports. iBio appears to be struggling financially, facing delisting (see Middle Market article) and floating stock with the aim of raising $10 million but securing only $500K in 2013 (but had $5 million cash on hand at year’s end; see the latest iBio 10Q). I looked at the US patents assigned to iBio and the three key ones are either co-assigned to Fraunhofer or have Fraunhofer employees as inventors. I am guessing this co-ownership resulted from iBio’s sponsoring of the expression system’s development at FCMB (with FCMB scientists being the actual inventors). Such an agreement and its recent modification to less expensive terms for iBio are mentioned in the company 10Q filing (iBio is committed to $1.5 million in payments to FCMB through 2015). I also noted the company is co-located with the FCMB.
All this suggests to me that iBio is a shell company whose main assets are patents on the expression system and future revenues are dependent on FCMB’s success in using the system to develop products with partners like MVI and FioCruz (a Brazilian governmental institute with whom FCMB has a contract to build a plant for a yellow fever vaccine; see my post, “Procurement Power”) and those products being licensed to a commercial entity to conduct full-scale trials, registration, distribution, and sales. If the FCMB wrote its contract with iBio correctly, or used the recent renegotiation opportunity correctly, it may have the right to pursue commercial partners independent of iBio, just owing a royalty. I hope this is the case so that FCMB can find partners for the malaria TBV and other products that are committed to global access. I assume that the FCMB management and board has thought through its product development strategy perhaps with help from the Gates and/or PATH (the latter have successfully launched one global vaccine, MenAfriVac®). There is no statement of a strategy on the FCMB website, and I noted its management team is all scientists (FCMB Leadership ) and its advisory committee is all solid citizens of Delaware with no pharma/biotech/medical experience (FCMB Committee).