Hale to a champion By Kim Ribbink Dr. Victoria Hale, who both conceptualized and founded a nonprofit pharmaceutical company, is a true pioneer. Her goal is to create affordable, safe, and efficacious treatments for infectious diseases that affect millions in developing nations. Already, her company has made huge strides in making this goal a reality. Victoria Hale In an industry focused on saving and improving lives, to single out an individual whose need to contribute puts her in a league of her own takes quite some doing. With the formation of a nonprofit pharmaceutical company, Victoria Hale, Ph.D., founder, chair, CEO, and chief scientific officer of the Institute for OneWorld Health, has carved out a truly unique niche for herself and her staff. The goal of OneWorld Health is to ensure that medical developments in the West are applied to healthcare needs in the developing world. The company’s focus is on providing affordable, effective, and safe therapies for infectious diseases. “During my career, I’ve witnessed a large number of potential drug leads that aren’t taken any further for a variety of reasons, including the Western market isn’t big enough for such a product, the company would have difficulty recouping its investments, or the drug didn’t fit a company’s portfolio,” Dr. Hale says. “These are all valid reasons for corporations, but oftentimes the science would suggest a drug candidate is good or has great potential to treat conditions that affect people elsewhere in the world.” The targets Dr. Hale has set for the company are carefully focused and well-considered. “We’ve taken on quite a challenge, to deal with the diseases that we’ve chosen and to work in the parts of the world that we have,” she says. “But there are many individuals associated with our organization, and many others who want to be associated with our organization, who are committed to developing treatments for infectious diseases. We can have an impact on disease burdens in the developing world.” OneWorld Health already has a major advantage: Dr. Hale is a leader who achieves what she sets out to do and who fosters innovation and change wherever she has been, whether at graduate school, in industry, or in government agencies. Taking and Giving Her Medicine From an early age, Victoria Hale was fascinated with the power of medicine, which led her first to pharmacy and then into clinical pharmacology. She was drawn to pharmacology because of the mathematical precision required. “Pharmacology involves monitoring the amount of drugs in an animal or person and how long they take to be eliminated,” Dr. Hale says. “This discipline also involves quite a bit of chemistry to determine how the drug is metabolized and what its half life is. Pharmacology requires calculating and predicting the optimal dose a particular patient will need to have efficacy with minimal adverse events.” But achieving optimal results in patients means ensuring a diverse population within clinical trials to begin with. When Dr. Hale began her career at the Food and Drug Administration, the subject mix for clinical trials was far from ideal, since most patients recruited for trials were men. In 1990, together with six women colleagues at the FDA, Dr. Hale set out to change that situation. “We asked then commissioner, David Kessler, and the directors within the FDA if we could ensure that women were included in clinical trials in larger numbers,” she says. “This campaign was well timed since the FDA was keen to bring about change and the National Institutes of Health also was looking into this issue.” The seven women – all M.D.s and Ph.D.s – were asked to document the number of women included in clinical trials. To achieve this goal, the group reviewed the patient-study populations for the drugs that had received approval during the 1980s to document that women were not adequately represented in clinical trials. At the end of the evaluation process, Dr. Hale’s group presented documentation showing there was a pattern of recruiting and studying young men in Phase I trials and that for Phase II and Phase III trials, the pattern showed a predominance toward studying men recruited from veterans’ hospitals, which resulted in the exclusion of women. “We concluded that there had to be different clinical-trial centers that would enroll women and there had to be a new sensibility and a new strategy and approach that this was important,” she says. Dr. Hale also contributed data that were used to write the NIH document on diversity in clinical-trial recruitment. The first target group was women, who represent about 51% of the population. Her research was then expanded to include minorities, children, and the elderly. “This was a very inspiring experience, one that showed me that a few committed people, if there is support at a high level, can bring about change,” she comments. After a five-year tenure at the FDA, Dr. Hale was ready to pursue other opportunities. While attending the University of California, San Francisco, for her Ph.D., she developed a love for the Bay Area. Dr. Hale also had the desire to work at a company where scientists played a major role in decision making. Genentech filled both criteria. Dr. Hale’s experience at Genentech opened new doors for the energetic scientist, providing her with industry experience and an opportunity to get involved with innovative research. She led three different sub teams for various projects, including two for neurotrophic factors and one for nerve-growth factors. While the latter project was halted in Phase III trials, it was a product that Dr. Hale was proud of and one she believes potentially could be developed later, possibly by another company should Genentech decide to sell the intellectual property rights. A Cautious Leap After three years at Genentech, Dr. Hale was ready to go out on her own. Before embarking on her next project, however, she decided to take a few months off to decide what she wanted to do. “It was during that time in 1998 that I wrote the strategic plan for OneWorld Health,” she says. “That was two years before I founded the company, but I wanted time off to clear my head and get words down on paper. After I wrote the strategic plan for OneWorld Health, I concluded that starting up a nonprofit pharmaceutical company was such a big deal that I needed time to sit with the plan, think about it, talk with others, and shop it around.” While cementing the plan for OneWorld Health, Dr. Hale started getting calls from people eager to use her FDA and industry expertise. So she established a consulting business, Axiom BioMedical, a development and pharmaceutical liability consulting organization. The business quickly grew, and by 2000 the company had eight employees. But the OneWorld Health call was strong, and in 2000 at the age of 40, Dr. Hale formed the nonprofit company. “In my years at the FDA and Genentech I had a great time but there was a mounting feeling of frustration that culminated in OneWorld Health, which is moving forward drug-development opportunities based upon their scientific merit,” she says. “The jolt to form the company came when I was talking to an African taxi driver in New York. I told him I was a pharmaceutical scientist and he said ‘you have all the money.’ It was painful to hear, and I decided right then that when I got home from New York I would visit an attorney and I would incorporate OneWorld Health.” The next step was to explain to people in the industry, the media, and other business sectors why such a company was needed. “We kept hearing that a nonprofit pharmaceutical company was an oxymoron, so it was a bit challenging getting past that,” Dr. Hale notes. “Now there’s a critical mass of people who understand why such an organization is needed.” The need is demonstrated by the overwhelming impact of infectious disease on the developing world. There is a scarcity of safe, affordable medicines to treat conditions such as leishmaniasis, Chagas disease, diarrheal diseases, and malaria. “The image of the pharmaceutical industry in many people’s eyes is bad, and we, as an industry, need to change this perception,” Dr. Hale says. “People in the industry want to help people, whether it be saving lives, extending lives, or improving the quality of patients’ lives.” Dr. Hale’s awareness that there was a need for someone to step into the fray was propelled not only by her experience as a scientist, but also by something more personal. “I have come to learn over the years of the number of children around the world who die before the age of five,” she says. “On some continents, 20% of children don’t reach their 5th birthday and, as a mother, that was extremely compelling to me.” Dr. Hale’s solution is extremely rare. She says with a nonprofit mission to bring drugs to market, OneWorld Health is like no other organization in the world today. “There are public/private partnerships, which bring the public and private sectors together to conduct research and development, but that’s not a corporate model,” she notes. With the vision in place and the goals established, Dr. Hale was ready to begin acquiring drug candidates for the company. But getting started presented some interesting challenges, one being getting the Internal Revenue Service to grant OneWorld Health nonprofit status. Until this issue was resolved, the company would not be able to receive funding. “The IRS couldn’t understand why the world needed a nonprofit pharmaceutical company when the pharmaceutical industry was so profitable,” Dr. Hale says. To convince the IRS, Dr. Hale presented a model that was familiar to the agency. “We used National Public Radio and public television, including programs such as Sesame Street and documentaries that exist thanks to those media, as a comparable model,” she explains. “That made sense to the IRS and the company received its nonprofit status.” With that crease ironed out, OneWorld Health was founded in July 2000. It received early investment from the Bill & Melinda Gates Foundation (so far $10 million). OneWorld Health also has a collaboration with the National Institutes of Health and has support from biotechnology companies such as Celera Genomics. OneWorld Health has launched its first two drug-development programs: final-stage testing in India of a promising new therapy to cure visceral leishmaniasis and early-stage testing of a new compound for Chagas disease in Latin America. OneWorld Health is vigorously pursuing new resources to fund development of its pipeline of promising drug leads. New therapies in malaria, Chagas disease, and diarrhea stand ready to be developed. “An extraordinary journey has just begun -to fundamentally change the health of the developing world – one disease at a time,” Dr. Hale says. Identifying Targets OneWorld Health’s first drug is paromomycin, an injectable antibiotic, to treat visceral leishmaniasis (VL), a deadly parasitic infection that afflicts 1.5 million people worldwide, primarily in India, and kills as many as 200,000 people each year, more than any other parasitic disease except malaria. Transmitted by the bite of a sand fly, VL attacks the internal organs. “If this disease killed the equivalent number of people in the United States, it would be the third-largest killer after heart disease and cancer and would cause more deaths than stroke,” Dr. Hale says. Dr. Hale reached an agreement with the World Health Organization/Tropical Disease Research Programme (WHO/TDR) to take paromomycin through late-stage trials. Paromomycin is an off-patent product previously approved as a broad-spectrum antibiotic. WHO had been given rights to the injectable form of paromomycin from Pharmacia, now Pfizer, for the visceral leishmaniasis indication. In August 2002, OneWorld Health received an initial $4.2 million grant from the Bill & Melinda Gates Foundation for the paromomycin project. An $80,000 grant from the Stanley Thomas Johnson Foundation in Berne, Switzerland, will fund a pediatric study to determine accurate dosing for paromomycin in children. OneWorld Health designed the trials, is analyzing the data, and will submit the drug to the Indian government for approval in 2005. WHO and OneWorld Health now jointly own the license to the injectable form of paromomycin. OneWorld Health is collaborating with WHO/TDR to develop paromomycin for regulatory approval in India, the country with the greatest disease burden in the world. The company is conducting a 670-patient, Phase III clinical trial for paromomycin as a one-time, 21-day treatment. Dr. Hale says the trial is showing promising results, and she expects trials to be completed by year end. If successful, paromomycin could be on the market by 2005. She is talking to a Dutch nonprofit drug distributor and to Indian drug companies about manufacturing the drug, ensuring affordability and high quality. Aside from the critical need for an affordable treatment, Dr. Hale says the company chose to focus first on paromomycin in India for several reasons. “There are several benefits of working in India,” Dr. Hale says. “There is a regulatory system; the drug controller of India – the DCI – has regulations similar to the FDA; because English is spoken, we can understand and work fairly easily with the agency; there are many talented physicians; and there is a very good medical system to treat this disease.” After gaining approval in India, the company will take the product to Nepal and Bangladesh, expanding its involvement in making drugs available. “It is not enough to produce, get approval, and manufacture a drug,” she says. Dr. Hale anticipates leading an effort to include goverments, WHO/TDR, and other organizations such as Médecins Sans Frontières with the goal of bringing the treatment to Sudan and the Horn of Africa. OneWorld Health’s second pipeline product is a protease inhibitor for the treatment of Chagas disease. Chagas disease, found only in the Western Hemisphere, is a parasitic disease transmitted by insects. It is named after Carlos Chagas, a Brazilian doctor who first described the disease in 1909. The protozoan parasite (Trypanosoma cruzi) enters the human body though broken skin. The parasites live in cracks and crevices of poor-quality houses, usually in rural areas. They emerge at night to bite and suck blood. The feces of the insects contain parasites that can enter the wound left after feeding, usually when it is scratched or rubbed, through transfusion with infected blood, or congenitally, from infected mother to fetus. Usually a small sore develops at the bite where the parasite enters the body. Within a few days, fever and swollen lymph nodes may develop. This initial acute phase may cause illness and death, especially in young children. More commonly, patients enter a symptomless phase lasting several months or years, during which time parasites are invading most organs of the body, often causing heart, intestinal, and esophageal damage and progressive weakness. In 32% of those infected, fatal damage to the heart and digestive tract occurs during this chronic phase. OneWorld Health’s product under development for treating Chagas disease is based on the donation of intellectual property from Celera Genomics. The product, K-777 (also called CRA-3316), has shown promising activity in both short-term and long-term animal models of Chagas disease. The National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIAID/NIH) has funded the research of this drug to date. In November 2001, OneWorld Health was granted all development rights to K-777 for use as an anti-parasitic agent by Celera Genomics, which acquired the company, Axys Pharmaceuticals, that patented the compound. OneWorld Health has received $1.5 million from the Bill & Melinda Gates Foundation to enable early-stage development of the K-777 compound. OneWorld Health is managing the synthesis of the new compound and will work with NIAID to complete the necessary preclinical animal testing of the drug. With successful results, OneWorld Health will file an investigational new drug (IND) application with the FDA. Once the IND is approved, OneWorld Health will perform a Phase I clinical trial to assess tolerability in human volunteers. OneWorld Health will seek international partners to develop K-777 for Phase II and Phase III clinical trials in Latin America if the drug is well tolerated. In another development, OneWorld Health is in late-stage negotiations with a small biotech company in San Francisco to develop a pediatric diarrhea drug. “One of our upcoming programs is a diarrhea drug program, and that is one where we share intellectual property with our partner,” Dr. Hale explains. “The drug will be developed by our partner for a western market indication, while OneWorld Health will develop it as a pediatric formulation for diarrhea in children under the age of 5 in the developing world.” The company’s diarrhea programs will begin in Bangladesh, at the world’s premier international research center for diarrheal diseases. OneWorld Health will also conduct a trial in India and will then move the program to Africa. The last of OneWorld Health’s major programs is in the area of malaria in pregnant women. Pregnant women are most at risk for infection. In Africa alone, 24 million pregnancies occur in malaria-endemic areas annually, and fewer than 5% of those women have access to effective interventions. Malarial infection during pregnancy increases the chance of maternal anemia, abortion, stillbirth, premature birth, intrauterine growth retardation, and infant low-birth weight, which is the greatest single risk factor for death in the first month of life. “The problem is that pregnant women are not an attractive population to conduct clinical trials on because of liability,” Dr. Hale says. “We’ve talked with two large pharmaceutical companies that believe their drugs are safe enough to be used during pregnancy but they’re unable to do the trials themselves. We can step in and do the trials for them.” As with any company, there is always a need to build the pipeline. Recently, OneWorld Health announced the transfer of intellectual property regarding another Chagas drug from Yale and the University of Washington. According to Dr. Hale, the company has received numerous offers – at least 150 unsolicited inquiries – mostly from academic centers to share their intellectual property. But, Dr. Hale points out that while the company is open to discussions with all groups, its interest is to focus on developing new medicines for infectious diseases that disproportionately affect the developing world. “It would be very easy to become distracted,” she says. “We’ve gone back and forth and have decided that the company will focus on drugs for infectious diseases right now.” Maintaining the Vision OneWorld Health has been warmly received by pharmaceutical scientists, many of whom have volunteered to contribute in various ways to the company’s projects. The next step is to gain greater corporate visibility. “Most companies in California know who we are, but at the national or international level we’ve only talked with three or four large pharmaceutical companies,” Dr. Hale says. “Some of those discussions have proved very fruitful, and we’ve had extensive conversations with one company in particular regarding partnership opportunities for treatments for malaria, leishmaniasis, and intestinal parasitic diseases.” As projects and opportunities expand, so too will the company. But Dr. Hale says she doesn’t want the company to get too big. “We have a nice nonbureaucratic, nimble organization, and I want to maintain this structure.” Currently, OneWorld Health employs 15 scientists, including chemists, microbiologists, and biostatisticians, and 10 support and development staff. Dr. Hale’s husband, Ahvie Herskowitz, a cardiologist, serves as chief operating officer, and he oversees clinical trials as the chief medical officer. Growth will allow Dr. Hale to set aside some of her many duties. Currently she is CEO, chair, and chief scientific officer. Dr. Hale’s intention is to bring someone in to take over the chief scientific officer position so she can focus on her role as CEO. “I think my role as a leader and visionary is more important at this stage for the company,” she says. Developing cures for diseases that claim so many lives in poorer nations is a noble goal and one that takes dedication and a willingness to persevere despite the challenges that arise. F PharmaVoice welcomes comments about this article. E-mail us at [email protected]. We’ve taken on quite a challenge, to deal with the diseases that we’ve chosen and to work in the parts of the world that we have. Worldwide Journey Throughout her career, Dr. Victoria Hale has striven to make a difference: whether that be by working to bring better health to the poorest members of society; ensuring that clinical trials are inclusive of all people, regardless of race or sex; or encouraging other women to excel in a predominantly male scientific culture. In an exclusive interview with PharmaVOICE, Dr. Victoria Hale, chair, CEO, and chief scientific officer of the institute for OneWorld Health talks about making significant social contributions, the people who inspire her, and how she seeks to inspire others. Aside from your work at OneWorld Health, you are involved in many forums and organizations and recently were named a Leadership Foundation Fellow of the International Women’s Forum for 2003-2004. What do you hope to bring to the forum and learn from this experience? I am thrilled to have the opportunity to participate in this fellowship and to meet extraordinary women who have done great things in the world of business. I am one of the few scientists involved in this forum, and I look forward to learning from other women what their paths have been like and how they make their decisions. I believe there also is an interest in hearing my reflections on how I made the decision to leave the classic pharmaceutical/biotech industry and consulting and begin an alternative pharmaceutical company. Where do you find inspiration? I’ve been fortunate to meet many like-minded people who are combining business with a social mission, especially through the Schwab Foundation for Social Entrepreneurship in Switzerland. The organization nominates and elects about 50 social entrepreneurs from around the world who work in environment, education, law, social justice, human rights, and health. These are visionary leaders who are bringing about change either at a grassroots level or national level. These people are truly inspirational for me. We’re all working in different areas, but the reasons for doing what we do are the same. I also have read many stories of women who began significant movements, for instance the suffragist movement. Reading their autobiographies and histories and stories has been particularly motivational for me. How have you remained active with the University of California, San Francisco, your alma mater? When I first founded OneWorld Health, I was inundated with e-mails from young women scientists who were completing their Ph.D.s, doing postdoctoral fellowships, or doing internships and residencies. They took encouragement that a woman would start such an organization. One of the early roles I took on, which was a bit of mentoring, was to encourage them to follow the path that was right for them, rather than follow my path. I give lectures intended to help women develop their own vision by first figuring out what it is they want to do and then making it happen. Also, as adjunct faculty member at the University of California, I devote about 12 hours a year to lectures on drug development and international health policy. (Dr. Hale also is an advisor to the World Health Organization on ethical review of human subject research and has been an advisor to the NIH on international health projects.) What is the next phase for OneWorld Health? Our next step is to expand the board of directors and grow the company to the next level. OneWorld Health is no longer a startup; the company is in a rapid growth phase. We’re looking to corporate executives to help us manage this growth, develop strategies, and make introductions and connections for us. But, I have no problem knocking on foundation doors and asking for millions of dollars. I don’t like to think about dollars on a day-to-day basis. I like to think about money at the program level and bringing in the grants to secure the stability of the organization’s programs. How do you start your day and how do you unwind? I try, when possible, to come into the office a little later. I begin work at home in a more relaxed manner. I’m with my two sons and two dogs, and they help me begin the day on balanced footing. The air in San Francisco is very fresh. It blows right over the Pacific Ocean, which we can see from our house. The one thing I do at the beginning and end of every day is to close my eyes and take a few deep breaths, just to remember how fortunate we are to live where we live and to have the opportunities that we do and keep that as an underlying foundation. Target Identification Chagas Disease: The world’s third-largest parasitic disease, Chagas is caused by the parasite Trypanosoma cruzi and is widespread throughout South and Central America; 100 million people are at risk for Chagas, with 16 million to 18 million currently infected and 45,000 deaths attributed annually to the disease. It is estimated that the economic cost of Chagas disease in endemic countries exceeds $8 billion annually. Current therapies are ineffective and prohibitively toxic. Visceral Leishmaniasis: The Leishmania parasite is responsible for three human diseases. The most deadly of the three, visceral leishmaniasis, is found primarily in the Indian subcontinent, Ethiopia, Kenya, Sudan, and Brazil. An estimated 1.5 million people are infected with visceral leishmaniasis; without treatment, the disease is fatal. As many as 200,000 people die each year of visceral leishmaniasis in India alone. Malaria: Malaria infects at least 500 million people and kills about 1 million people annually, mostly children. In most malaria endemic areas of the world, pregnant women are the main adult risk group for infection. Sub-Saharan Africa bears 90% of the global malaria burden. At least 24 million pregnancies occur in malaria endemic areas of Africa each year, yet less then 5% of pregnant women have access to effective malaria interventions. Diarrheal Disease: Diarrheal disease is the second-leading cause of death worldwide in children under 5 years of age, accounting for an estimated 2 million deaths annually. Caused by bacterial, viral, and parasitic agents, more than 4 billion acute cases of diarrheal disease occur annually, primarily in children in developing countries. There are very few, if any, antidiarrheal drugs being developed to treat life-threatening diarrheal disease in children. Cutaneous Leishmaniasis: The most common of the leishmaniases, the cutaneous form threatens 350 million people worldwide, with highest incidence in Afghanistan, Brazil, Iran, Peru, Saudi Arabia, and Syria. Between 1 million and 1.5 million new cases of cutaneous leishmaniasis occur each year, primarily in children. Although this disease does not kill, it significantly disfigures those infected. Victorious Pursuits 2000-Present. Founder, CEO, Chief Scientific Officer, Institute for OneWorld Health, San Francisco 2000-1999. Chief scientific officer and cofounder, Axiom BioMedical Inc., San Francisco 1999-1994. Scientist, Pharmacological Sciences, Genentech Inc., South San Francisco, Calif. 1994-1990. Senior reviewer, CDER, FDA, Rockville, Md. 1990-1985. Graduate student, Department of Pharmaceutical Chemistry, University of California, San Francisco 1985-1983. Clinical and staff pharmacist, Oncology Center, Johns Hopkins Medical Institution, Baltimore Appointments 2003-Present. President, Alumni Association, Graduate Division, University of California, San Francisco 2002-Present. Adjunct associate professor of biopharmaceutical sciences, University of California, San Francisco 2002-1999. VP, Alumni Association, Graduate Division, University of California, San Francisco 2000-1998. Member, board of directors, Quan Yin Healing Arts Center of San Francisco 1994-1993. Member, Committee for the Advancement of Scientific Education, Center for Drug Evaluation and Research, FDA Education 1990. Doctor of Philosophy, University of California, San Francisco 1983. Bachelor of Science in Pharmacy with High Honors, University of Maryland Fellowships and Awards 2003-2004. Schwab Foundation for Social Entrepreneurship – Outstanding Social Entrepreneur 2003-2004. International Women’s Forum – Leadership Foundation Fellow 2003. World Academy of Arts & Sciences – Fellow. Tech Museum of Innovation – Laureate 1999-1994. Three Product Development Awards, Genentech Inc. 1993. Public Health Service Group Recognition Award, Food and Drug Administration 1990-1986. NIH Pharmacological Sciences Training Grant, Trainee Fellowship, University of California, San Francisco 1990-1987. Graduate Fellowship, American Foundation for Pharmaceutical Education, University of California, San Francisco 1987. Long Excellence in Teaching Award, University of California, San Francisco 1983-1981. Rho Chi Honor Society, University of Maryland School of Pharmacy Dr. Victoria Hale – Resume An extraordinary journey has just begun – to fundamentally change the health of the developing world one disease at a time. OneWorld Health focuses on developing new medicines for infectious diseases that affect the developing world.

1993. Public Health Service Group Recognition Award, Food and Drug Administration 1990-1986. NIH Pharmacological Sciences Training Grant, Trainee Fellowship, University of California, San Francisco 1990-1987. Graduate Fellowship, American Foundation for Pharmaceutical Education, University of California, San Francisco 1987. Long Excellence in Teaching Award, University of California, San Francisco 1983-1981. Rho Chi Honor Society, University of Maryland School of Pharmacy Dr. Victoria Hale – Resume An extraordinary journey has just begun – to fundamentally change the health of the developing world one disease at a time. OneWorld Health focuses on developing new medicines for infectious diseases that affect the developing world.