[This article was published in 2009 and updated in May 2012. Read the update here.]
An oral amphotericin B (AmpB) formulation is showing promising results in preclinical studies that could one day provide the developing world with a treatment for leishmaniasis, a devastating disease that has a significant impact on indigent populations where the disease is endemic. An oral AmpB formulation would allow the therapy to be brought to the patient instead of requiring travel to the clinic, and it does not appear to have the associated renal toxicity of available intravenous (IV) formulations, putting an affordable, less toxic therapy within reach of the developing world for the treatment of leishmaniasis.
The success to date is due in no small part to global access principles that bind researchers, university staff and students, and the licensee of the technology in a common bond—to ensure this novel, lipid-based oral formulation of AmpB reaches the developing world where, according to World Health Organization (WHO) statistics, leishmaniasis currently threatens 350 million people in 88 countries.
The licensing deal, the first among Canadian universities in accordance with these global access principles, was signed in 2008 between iCo Therapeutics Inc. and the University of British Columbia (UBC), both of Vancouver, British Columbia, Canada. In return for the worldwide exclusive rights to develop and sell the oral reformulation of AmpB (termed iCo-009 by iCo Therapeutics) in the developed world as a treatment for bloodborne fungal infections, iCo Therapeutics ensures the availability and accessibility of a suitable formulation for the developing world to treat leishmaniasis.
Leishmaniasis: A Global Threat
Leishmaniasis, a parasitic disease transmitted by the bite of the sand fly, infects an estimated 12 million people today, and about two million infections occur annually. It has a wide range of clinical symptoms:
- Cutaneous leishmaniasis, the most common form of the disease, causes ulcers on the face, arms and legs. While the ulcers heal on their own, they cause serious disability and leave severe and permanent disfiguring scars that lead to discrimination, stigma and substandard living conditions. Epidemics are especially devastating in refugee camps.
- Visceral leishmaniasis, the most severe form of the disease, attacks the internal organs, and, if left untreated, is fatal within two years.
An ominous global trend is developing, where persons with HIV become coinfected with visceral leishmaniasis, which accelerates the onset of AIDS by cumulative immunosuppression and by stimulating replication of the virus. According to the WHO, visceral leishmaniasis is no longer restricted to endemic areas and the number of cases of visceral leishmaniasis and HIV coinfection will continue to rise. For example, up to 70 percent of adult cases of visceral leishmaniasis in southern Europe are linked to HIV infections, and 35 percent of all leishmaniasis patients in some areas of Ethiopia are coinfected with HIV, with an indication that it is spreading to neighboring countries such as Sudan.
Where There’s a Will, There’s a Global Access License
The promising oral AmpB formulation was discovered in the Wasan Lab at UBC by Kishor M. Wasan, Ph.D., professor, Canadian Institutes for Health Research/iCo Therapeutics research chair in drug delivery for neglected global diseases, and chair in the Division of Pharmaceutics and Biopharmaceutics, and Ellen Wasan, Ph.D., adjunct professor in the faculty of pharmaceutical sciences also at UBC. The Wasans devised an oral formulation that showed promising lab results with minimal side effects, a significant improvement on the 50-year-old treatment that is expensive, must be administered by IV infusion and is highly toxic. The significance of this innovation grew when they realized it was ideal for application in both the developed and developing world.
The next step for moving the Wasans’ discovery from the lab bench through to commercialization might have followed the traditional route charted by most technology transfer offices that patent and license university-based innovations. However, in 2007 UBC’s University-Industry Liaison Office (UILO) had just become the first university in Canada to develop a flexible framework to ensure it provides global access to relevant technologies. The new Global Access Principles, developed in collaboration with key senior administrators and the student-led UBC Chapter of the Universities Allied for Essential Medicines, establishes practical mechanisms and partnering strategies for UBC technologies to maximize their societal impact.
So when iCo Therapeutics, a publicly traded biotech company, approached the UILO about the Wasans’ discovery, they needed to find a win-win solution that would achieve both organizations’ objectives.
“Our goal was to have the new oral AmpB formulation licensed to a company that would agree and be able to not only develop the formulation in the developed world for fungal infections, but also develop the technology in the developing world for the treatment of leishmaniasis in accordance with the Global Access Principles adopted by UBC,” says Ian Bell, a technology transfer manager of the UBC UILO, which assists UBC researchers through core activities of sponsored research and technology transfer to increase the academic, societal, environmental, economic and financial impacts of their research.
John G. Clement, Ph.D., chief business officer and director of iCo Therapeutics, adds, “Our business model is focused on redosing or reformulating drugs with clinical history for new or expanded indications. The oral amphotericin B program is an early proof of concept of the underlying drug delivery technology and provides iCo with an opportunity to expand our product pipeline and provides a new way for the company to explore other drugs that can be converted from the parenteral route of administration to the oral route.”
The licensing negotiations — described as very productive and positive by those involved—occurred over roughly a four-month timeframe and involved various parties, including UILO, the UILO external legal counsel, iCo Therapeutics and its external legal counsel.
The most critical negotiation issues involved the licensing terms related to:
- Reasonable development time lines — With the need to move both a developed and developing world formulation forward, the partners established a development time line to ensure that the company could pursue a product for the developed world that could financially support the company, while at the same time, ensuring that the product for the undeveloped world would not be pushed aside or pursued in favor of the other.
- Formulation for developing world — The partners agreed to a process whereby iCo would either solve any issues in its obligations to create a developing world formulation, or UILO would have the ability to step back in and access the rights to develop the formulation for the developing world.
- Parallel imports — In an attempt to prevent or reduce the risk of parallel imports, a matter of great concern to iCo Therapeutics, the partners agreed that different formulations would be developed for the developed and developing worlds. The nature of the formulation actually lent itself to this strategy because of the different requirements, such as disease target, and temperature and stability.
Once these issues and the financial terms were agreed upon, much of the discussion centered on the appropriate global access language, since the desire to increase global access for health related innovations and the realities of working with industry to commercialize them takes more than a standard licensing structure. “UBC granted iCo Therapeutics the worldwide, exclusive license to the UBC technology,” says Bell. “Under the license agreement, iCo’s global access obligation is to ensure availability of a formulation of the UBC technology for treating leishmaniasis in the developing world at a subsidized price.”
Public and Private Partners
In May 2008, the UBC UILO signed its first licensing agreement in accordance with Global Access Principles when it partnered with iCo Therapeutics to advance the oral formulation of AmpB. As the Wasans’ discovery moved from the lab bench through to licensing, it also involved several public and private organizations:
- Federal government of Canada — Provided research funding to the inventors through the Canadian Institutes for Health Research and the National Research Council of Canada Industrial Research Assistance Program (NRC-IRAP), designed to provide funding and support to Canadian small and medium-sized enterprises. iCo Therapeutics also received NRC-IRAP funding to support development activities related to the oral formulation.
- Canadian Research Network and Mathematics of Information Technology and Complex Systems — Provided funding for a UBC postdoctoral intern to work with iCo Therapeutics to develop the technology further.
Since signing the license agreement in 2008, iCo Therapeutics has moved development of the formulation forward. Some of the work includes collaboration with the Consortium for Parasitic Drug Development—a Bill & Melinda Gates Foundation-funded consortia based at the University of North Carolina at Chapel Hill—to test the oral formulation in a leishmania model. The results of this testing showed that the oral formulation was almost 99 percent effective in clearing the infection. iCo Therapeutics also held a pre-IND (investigation new drug) meeting with the U.S. Food and Drug Administration to clarify the company’s clinical plan.
iCo Therapeutics also is in the planning stages of chemistry, manufacturing and controls, scale-up and current good manufacturing practice, and good laboratory practice safety and toxicology work to support a IND application.
Flexibility, Support and Willingness Key to Success
The UBC UILO has had some experience over the years with global access and individual licensing programs and projects. One program involves a UBC-based researcher who collects marine and plant biota, such as sea sponges from Papua New Guinea, and then isolates potential therapeutic compounds from them, with a portion of economic returns going back to the country of origin. The UBC UILO also manages some projects with the aim of developing essential medicines for the developing world that received a Grand Challenges in Global Health grant from the Foundation for National Institutes of Health and the Gates Foundation.
But now, with adoption of Global Access Principles and the licensing agreement to allow iCo Therapeutics to commercialize the oral formulation of the drug AmpB, UBC is part of a growing number of universities and nonprofit research institutes that have either implemented or are considering adopting socially responsible licensing practices.
“Looking back over the hard work and discussions that culminated in this licensing agreement, I think three key elements stand out—flexibility, support and a willingness to do something good for those who are less fortunate,” says Bell at the UBC UILO. “And, in a way, it was the result of a perfect storm and a little luck.”
Key learnings that came out of this licensing agreement include:
- Flexible Language: This win-win scenario was based on mutual trust and iCo Therapeutics being receptive to a creative and flexible approach used by the UBC UILO in developing the licensing terms and language that were acceptable to all parties. There is not a standardized approach to drafting or enforcing global access policy language in licensing agreements.
- Support: The UBC UILO was pleased by the support it received for the Global Access Principles by external stakeholders during the review process. iCo Therapeutics welcomed the global access language in the license and its investors agreed the global access language and relationship with UBC were a benefit to all.
- Willingness to Do Good: Having an industry partner with a global stewardship priority is the foundation for a successful agreement allowing a company to advance technology for the developed world, while making the technology available to resource-constrained countries through subsidized pricing.
Support from senior administration, both at the university administration and technology transfer office, also is critical to the adoption and implementation of global access principles that guide how licensed university-based technology may impact the developing world. This support allowed for the drafting of appropriate global access licensing terms and is helping to establish a new metric to measure the effectiveness and global influence of UBC and the UILO.
“We are very excited by the potential of iCo-009,” says iCo Therapeutics’ Clement. “We are proud to know that iCo-009 could save and improve the quality of life in both the developed and developing worlds.”
By David Perilstein