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Solid as a Rock: Creating a Strong Foundation for Developing First-in-Class Treatments to Fight Aggressive Cancers – A Chat with Elaine Sullivan, Co-Founder & CEO, Carrick Therapeutics

By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)

In the life sciences, disruptive innovation is no longer the exception; it’s the rule. One global R&D executive known for successfully driving innovation is Elaine Sullivan.

Sullivan – who has 25 years of experience in the pharma industry – has led R&D teams at Eli Lilly and AstraZeneca, and worked internationally in the US and the UK, developing new molecules in therapy areas such as virology, cancer, ophthalmology, respiratory and inflammation.

Today, she is leading the charge behind Carrick Therapeutics, a start-up whose ambitious plans include becoming Europe’s premier oncology player. Carrick is developing an innovative portfolio of first-in-class treatments that are advanced through understanding the mechanisms that cause cancer and resistance, tailored to an individual patient’s tumor. By linking a network of clinicians and scientists in internationally leading research institutes and hospitals, Carrick plans to use its multi-asset portfolio to drive the development of these ground-breaking cancer therapies from laboratory to clinic.

Carrick has managed to assemble world-class cancer researchers and drug development experts, and has attracted some of the most renowned providers of early stage capital. In October 2016, the company received $95 million in funding, which was led by ARCH Venture Partners and Woodford Investment Management.

I recently spoke with Sullivan, who gave a sneak peek behind Carrick’s new approach to cancer therapies, the company’s strategy in building Europe’s leading oncology company, as well as what drives her passion for science.

Rich Soll: You’ve had such a tremendous rise in the industry. Can you share with us your personal journey?

Elaine Sullivan: I’ve always had a huge passion for science. I was incredibly fortunate to do my Ph.D. with the late Professor Ken Murray, who was one of the founders of Biogen. During that time, he really instilled in me and the group a great belief that everything is possible, and he was one of the most inspirational people I’ve met. To him, life was always about inspiration, biotech, great science, and believing anything’s possible. He was a great mentor and stimulus from the beginning of my career.

Rich Soll: How did your career develop from AstraZeneca and then ultimately lead to Lilly?

Elaine Sullivan: Throughout my career at AstraZeneca, I was really fortunate to be supported in creating and developing functions which were about transformational change in R&D. As vice president, Science & Technology at AstraZeneca, my priority was identifying and integrating novel drug-hunting approaches to successfully reduce compound attrition in the clinic and significantly decrease the time to deliver new molecules.

Then, as vice president, R&D New Opportunities, I established the first virtual therapy area in AstraZeneca to pinpoint new disease areas and future health care trends, create new therapeutic applications for multiple molecular entities, and advance them into the clinic. Getting into the clinic – that’s always the priority.

At Eli Lilly, where I was vice president of Global External Research and Development, the global workforce I led was focused on delivering access to external innovation. We did this, firstly, by identifying, evaluating, and acquiring therapeutic molecules and technologies, and secondly, by creating and managing Lilly’s external R&D portfolio via venture, equity, and strategic partnerships.

Rich Soll: So now we get to Carrick. Carrick is very different in the sense that it’s an outsourced model with key strategic partners; it almost breaks the mold compared to what you’ve been used to, where internal resources were either available or accessible to carry out execution on the projects you were working on. How is Carrick’s model unique?

Elaine Sullivan: One of the cornerstones of Carrick was to create a leading oncology company and to build a company with a strong foundation that we could scale.

We have an excellent, experienced R&D team with an outstanding track record in developing innovative medicines via an outsourced model, collaborating with a network of world class scientists and clinicians in top institutions such as Cambridge University, Imperial College London, Oxford University, and the Christie Hospital in Manchester. Carrick Therapeutics also has a strong association with Cancer Research UK, the world’s leading cancer charity.

In addition, Carrick Therapeutics has assembled a team of internationally recognized clinicians and scientists for the company’s scientific advisory board, which is chaired by Sir John Bell (Regius Professor of Medicine, University of Oxford).

To enable a rapid execution and enhanced selection of compounds across the R&D value chain, we have a unique combination of platform technologies and strategic alliances. That means we can select the best compounds to achieve clinical proof of concept faster and at lower cost.

By pulling our R&D team together, plus the company research engine, we’ve really moved incredibly fast, and we’ve moved quickly because instead of building from scratch the infrastructure and the labs, we’ve almost immediately created a great network of people that have the expertise and facilities at hand. The other advantage we’ve had is that we’ve had enormous support from the scientific community both in Europe and in the US, which has been exceptional.

Carrick is Irish for stone, which represents our vision to create a strong foundation on which to build a successful company.

Rich Soll: What’s interesting to me is you have a terrific investor team and scientific staff. How do you differentiate yourself from other companies in the oncology space?

Elaine Sullivan: For me, the differentiation will always be the science and the compounds that we are progressing. Our initial projects are in aggressive forms of cancer, and adaptive resistance. The projects will have utility in breast, colon, and ovarian cancer, where there is a significant clinical need – for example, the five-year rates of survival are only 50%. We’re passionate about driving change, and with respect to the molecules, the novel mechanisms, our collaborators, and talent we have around us, we feel really confident that we can and will be unique.

Rich Soll: What are your near-term milestones?

Elaine Sullivan: We are getting ready to go into the clinic with a very exciting molecule, and our near-term milestone is to demonstrate a suitable pharmacokinetic and tolerability profile, and then move quickly into an efficacy study to demonstrate a positive effect on patients. We’re also looking for two other clinical assets to accelerate our portfolio build.

Rich Soll: What will Carrick look like three years from now?

Elaine Sullivan: Carrick, in three years’ time, will have compounds that will have read out in the clinic, and we will have continued to move other great projects into the clinic – that’s our clear strategy.

Rich Soll: How important is having the right strategic partners and academic collaborations in fighting these aggressive cancers?

Elaine Sullivan: It’s extremely important because this encourages synergy between us and our collaborators – academic and industry partners – to help us identify those novel signals, and give us that insight into different cancer types and their biological mechanisms. So it’s really important to make sure that the academic partners and Carrick are really linked together, so that when you see something novel you grasp it and incorporate those findings into your R&D programs. That’s what I love; it is hugely exciting.

Rich Soll: We describe cancers historically through several different characteristics, and now we have about 10 characteristics. Do you expect more fundamental additions to this through your own research?

Elaine Sullivan: Yes, I do. We’re working very much on adaptive resistance, and you see that occurring frequently in cancer. It’s about getting in before that resistance kicks in with another molecule, another mechanism. We want to help people live well and long despite their cancer condition.

Rich Soll: Do you see the cancers you’re working on as giving patients longer time or do you see some fundamental breakthroughs in these aggressive cancers that may ultimately lead to cures?

Elaine Sullivan: Of course the ultimate aim is to cure the most advanced forms of aggressive cancer, which is taken as being disease-free after five years. This is sometimes seen for some patients treated with agents designed to target specific molecular changes as we begin to understand the drivers of cancer – for example, Glivec in CML. However, what we’re also trying to do is effect transformational change in cancer care for patients, helping people live well and longer with cancer.

Rich Soll: Are there any personal motivations behind your passionate work with aggressive cancer therapies?

Elaine Sullivan: My father had very aggressive stomach cancer and was given a very poor life expectancy. He was offered a new therapy which included a constant infusion of Fluorouracil (5FU) using a portable pump. He was very brave and was determined to try any treatment that would help him.

His courage and determination to beat the disease was striking, as well as his great humor, which was inspirational. He was intrigued by the therapy, and as an electrical engineer he also worked with the clinical unit to offer suggestions on how to improve the design of the pump. He lived another three years after his diagnosis.  My three children were born during this time and he got know them, which simply wouldn’t have happened if he hadn’t had that treatment. It has hugely affected me, my children, and my whole family.

Rich Soll: What keeps you up at night when you think about Carrick and what you need to accomplish?

Elaine Sullivan: It’s an incredibly exciting opportunity. Carrick is the right company at the right time. What keeps me up at night is thinking about how I can help make sure that the great team and collaborators we have all work together successfully to obtain maximum benefit from our portfolio for cancer patients.

Rich Soll: Do you having any closing thoughts you’d like to share?

Elaine Sullivan: I would just stress that Carrick’s mission is creating Europe’s leading oncology company, and we believe that we have the strong foundation and portfolio that will enable us to achieve our goal. The value of our company is built on our vision and drive to successfully use our portfolio to develop new market-leading treatments, creating transformational change for cancer patients.


Brave Science: Putting the ‘Hutzpah’ in Early-Stage Drug Discovery – A Chat with Ehud Gazit, Academic Director, Blavatnik Center for Drug Development, Israel

By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)

From developing new paradigms for early-stage drug discovery for rare and common diseases to fostering the convergence of peptide nanotechnology, and launching scientific experiments in space, Israeli biochemist Ehud Gazit is wearing many hats these days.

In his role as academic director at the newly-formed Blavatnik Center for Drug Discovery (BCDD) at Tel Aviv University in Israel, Gazit is leading efforts to provide the missing link that may enable many scientific discoveries to evolve into beneficial drugs. The Center is uniquely dedicated to translational science by helping researchers turn their discoveries into effective pharmaceuticals.

Gazit – also a biophysicist and nanotechnologist – stays active in his university lab, which explores biological and bio-inspired molecular self-assembly. The lab studies the organization of biological systems in diverse fields, including amyloid diseases, diabetes, virology, and metabolic disorders.

Gazit – who has been a faculty member at Tel Aviv University since 2000, after completing his postdoctoral studies at MIT – also serves as the Chair for Biotechnology of Neurodegenerative Diseases at Tel Aviv University, and heads the Laura Schwartz-Kipp Institute for Biotechnology.

Today, he is also leveraging his former role as the Chief Scientist of the Israeli Ministry of Science and Technology, as well as leadership positions at Tel Aviv University, to bridge science, government, and industry for the greater good of the community.

I recently had an engaging conversation with Gazit, who explained further the mission of the BCDD, his role as a public servant, and how a combination of out-of-the-box-thinking and ‘hutzpah’ can advance science.

Rich Soll: To set the stage, let’s talk a little bit about Israel. The country has several million people and is highly entrepreneurial, highly educated, highly motivated, with professionals in the life sciences and biomedical sciences, and is producing some of the world’s most cutting edge  science and innovative products, which was captured a number of years ago in the book, The Start-Up Nation. In your view, what are some of the top factors that contribute to this disproportionate influence by Israel in the sciences and biomedical research?

Ehud Gazit: I think there are some things that are quite unique that may signify the way that Israel is seen. First, I think it’s out-of-the-box thinking – this is something in Israel that is very clear. Some of it is due to lack of resources.  I remember during my time at MIT, I took these courses on out-of-the-box thinking, and then I realized that maybe Israel needed in-the-box thinking; out-of-the-box thinking comes very natural here.

Secondly, something that may be related to this is the informality which allows Israelis, many time young students and young faculty members, to challenge many of the paradigms. In order to achieve innovation, you need this courage, the hutzpah, to allow yourself to challenge well-known paradigms.

Thirdly, I think it’s the excellent public education system. In Israel, me and most of my graduate students, and my fellow faculty members, we are all products of an excellent public education system, especially the higher education. On a modest budget, we’re able to give first-rate education open to everybody independent of the socio-economic background. This is how you get the most out of the population. I think that every child, even if they grow up in a less favorable environment, deserves and can enjoy a high level education and get into a university – for about $2,000 a year, you get a first-rate education.

Rich Soll: Does having limited resources breed a new way of thinking because you’re faced with this unique challenge?

Ehud Gazit: Yes, you need to be very focused; you need to be very creative. When the resources are limited, indeed, you need to try harder, you need to be focused, and you need to know where you are going. It’s less of a fishing expedition, but rather very directed and precise science.

Rich Soll: Despite having all those limited resources, look at what you’ve done. And your work has such practical consumer implications, such as self-assembly as it relates to fast cell phone charging applications. Can you give us some other examples of this type of work?

Ehud Gazit: We applied a systematic reductionist approach to identify the most fundamental recognition modules in nature. This work had inspired hundreds of groups around the globe to follow our discoveries. Although our quest was for basic biological questions, it turned out to be very important also technologically as some of the minimalistic assembly units form nanostructures with unique mechanical, optical, piezoelectric, pyroelectric and semi-conductive properties. Scientists are very creative in using the nanostructures that we had identified. I have this Google alert on ‘diphenylalanine,’ the module reported in our 2003 Science paper, and every week I get all kinds of applications you couldn’t even think about. This includes the fueling of nano-boats, production of electricity by pressure or heating, and the use of the optical properties to measure very low temperatures like near absolute zero.

Rich Soll: Can you elaborate on some of the themes that you’re examining and the implications of your findings?

Ehud Gazit: We are working on diverse disciplines. One may think that it doesn’t make sense working simultaneously on energy storage devices, superhydrophobic surfaces, biosensors, biomaterials, disease mechanism and drug discovery, but actually they all have a common denominator, which is our quest to understand the most fundamental modules that mediate and facilitate molecular self-assembly at the nano- and micro-scales. I call our research minimalistic and systematic, not biased, so we take complex questions, let’s say recognition by proteins or nucleic acids or other organic molecules, and we try to cut it into the smallest pieces that allow the molecular recognition and self-assembly. It provides us with insights to mechanisms of disease. It helps us to understand how you obtain interesting physical phenomena by identifying these elements. We understand fundamentals of supramolecular polymers chemistry.

One of the things we study is the assembly of structures using the guanine, those parts of DNA and RNA that allow the recognition between the bases. By a systematic, minimalistic, non-biased approach, we go into guanine, which is one of the four nucleobases of DNA, but it is also being extensively used in nature. Evolution has realized over and over again the unique physical properties of guanine assembly. Guanine is the structure that allows the physical coloring of fish, allows chameleons to change their color rapidly, and it serves as reflectors in nocturnal reptiles like crocodiles. We use guanine-based building blocks to obtain various architectures at the nano-scale with remarkable and tunable optical properties.

Rich Soll: I read recently that you were involved in some space rocket experiments. Can you tell us more about that? 

Ehud Gazit: Yes, it’s part of our collaboration with Space Pharma, an Israeli start-up company looking to explore biological activities in space, on the conditions of no gravity. We sent a system based on our small dipeptide system I mentioned and we are trying to see what will be the effect of no gravity on the substance that we put on the physical properties. I do hope that we will see alternative architectures and new physical properties at zero-gravitation conditions.    

Rich Soll: This is outstanding science.  Have new tools and knowledge increased the possibilities and functions of self-assembly?

Ehud Gazit: Yes, one emerging area is the ability of metabolites to self-assemble. It’s been realized for many years that metabolites can crystalize. This is a case of gout, kidney stones, but now we have new tools to understand the formation of the structures, to understand how alternative amyloid-like structures could be formed within the metabolite, and maybe provide new direction to disassemble these structures. We provide new insights into the mechanism of inborn error of metabolism disorders in which there is accumulation of metabolites. So I think, over the last two decades, there has been an important realization from the scientific and medical community of the role of protein self-assembly in neurodegenerative disorders. But I think it’s much wider, looking at molecular self-assembly in general, metabolites, proteins, and lipids.

Rich Soll: So let’s talk more about BCDD. How did it get started and what is its mission?

Ehud Gazit: We’ve been provided with a very generous donation from Len Blavatnik, who is a great supporter of science. Through my experience as a researcher, and as an administrator at a university involved in tech transfer, it became apparent that what is missing in Israel is the very early stage of drug discovery. By engaging in an inclusive, multi-disciplinary environment, we target not only the researchers who are familiar with drug discovery and development, but many others who are excellent scientists but discovered a new biochemical agent, a new receptor, or a new enzyme, but are not familiar with the first steps that could allow these wonderful discoveries to be translated to the development of drugs. In a recent call, we had nearly 30 applications from different fields.

The center is also open to other communities. We often host high school students, very gifted ones, who are being exposed to activities in drug discovery. We also provide information and testing for individuals with rare disease. We are looking for targeted therapy; we try to understand the basic mechanisms of rare disease, and we are in constant dialogue with patient organizations and others. Another activity of the center is organizing conferences. We have had conferences on rare disease, on computer-aided drug design, and drug discovery. We are having another annual meeting on drug discovery and development.

Rich Soll: By being a center, you can draw in research from the university. Is that working so far?

Ehud Gazit:  Yes, we are able to include in the drug discovery community excellent researchers in the university who were not part of drug discovery and development activity. While Tel Aviv University is now doing remarkably well in terms of publications, we are ranked constantly somewhere between 15-to-20 in the world in terms of citations, and have many European Research Council (ERC) grants, even though the number of drug discovery programs is not high.

Through a collaborative approach, we can provide unique service and we can provide our own directions in terms of fragment-based drug development, natural products, and screening for individuals with rare disease. I really want the center to be involved particularly where we have some core expertise that is already appreciated by the industry.

Rich Soll: What do you see as the strengths of the center?

Ehud Gazit: Firstly, it is providing, under one roof in a very efficient way, the full direction needed for drug development beyond the screening, medicinal chemistry and computer-assisted drug design. For many of the projects we have an integrated approach. The center is turning excellent multi-disciplinary science into therapeutic leads. On a daily basis, we sit together – the computation scientists, the high through-put screening specialists, the biologists and the medicinal chemists – in the same room speaking about the challenges, discussing with the faculty members, and people coming from the industry what their needs are. It’s a truly integrative approach.

Secondly, we are located in the middle of the campus, the place for people to stop on their way to their lab, and for students to come by. We are just above the central lecture hall of the university so we have many times students, even freshman, coming to the center to learn about the importance of drug discovery and wanting to be part of this activity.

Thirdly, it is our understanding that you need to provide the full spectrum from basic science to applied science.

Rich Soll: Are there similar centers in Israel? How would you differentiate BCDD versus others?

Ehud Gazit: In Israel there is the National Center for Personalized Medicine at the Weizmann Institute of Science, which provides excellent services, and which we have very good connections with. We see ourselves being more of a research institute and less of a service provider. We try to have our own uniqueness and direction. In our case, there is a stress on an interdisciplinary approach and a close connection to patients. Other centers are excellent and we are coordinating our efforts with them, all for the benefit of science and the benefit of patients.

Rich Soll: You’ve had a very illustrious career –  a great educational background, terrific research, a strong publication record, and then on your career side, rising all the way up to the Chief Scientist  of the Israeli Ministry of Sciences. Can you share your personal journey?

Ehud Gazit: Similar to statistical thermodynamics, these were random walks. I always knew I would be a scientist, but being chief scientist for the Ministry of Science, vice president for research, these things were not planned. As part of my career, I joined Tel Aviv University after my post-doc at MIT. I grew through the ranks, had tenure in two years and became a full professor in about six years. And then I got this offer a very short time after I joined the university, about seven years, to serve as the vice president of research. You cannot refuse such an offer.  I decided, quite to the surprise of many people, to assume also administrative roles. I was vice president of research, and chairman of the technology transfer office, but always keeping my lab active. Then came the offer from the Minister of Science to serve as chief scientist. Again, I could not refuse the offer. It was a way to serve the scientific community; I saw myself as a civil servant.

Rich Soll: What were some of your accomplishments and what lessons did you learn from having these leadership roles?

Ehud Gazit: I learned that science is truly bi-partisan, and something you could get a consensus from left to right, and center. There is an appreciation of the role and importance of science. I also learned that you must motivate players, at the political level and the administration level; you need to motivate people and convince them you can make big changes. I’m not an engineer, but one of the things that I decided was missing in Israel is a type of funding program that is specifically targeted to engineering science. We found so many times that engineers were doing either applied science or very basic science, but less of what I would denoted as ‘engineering science.’  So we established this fund for engineering science.

One of the other things that I pushed forward was international and bilateral agreements between Israel and other countries. I realized that when you convince people about what you do and build up the right coalition, it’s not political, but rather based on the understanding of the importance of things that you think should make a difference. It was really quite an exciting time. Scientists are usually not exposed to government and parliament meetings and hearings. It makes you understand the importance on making science accessible to the general public. You need to let the people understand why they invest so heavily in scientific activities. It’s important to bring the message to the public.

Another thing for me that was very important was to have a public education system in Israel as open as possible to all parts of society, so we have research and development centers all across the country including several in the Arab sector that I specifically supported, as well as special programs for the advancement of women in science.  For me, it was a great opportunity to serve the public at the largest extent.

Rich Soll: How are you implementing those lessons learned to the BCDD?

Ehud Gazit: One thing that I realized is the importance of bringing together people from different disciplines. The BCDD is much about inter-disciplinary, and proving the full spectrum, from basic science to applied science. We also decided to focus on several subjects and one of them is rare disease, in which I see as a remarkable importance from a scientific point of view, but also as a service to society. I see our interaction with the general public, from parents to children with rare disease, for people who carry a mutation and looking for a solution. It is very clear for us that it’s not only about science, but we are there for the people. So in our decision to focus on rare disease and rare disorders, our research is also related to our service to the community.

If I can summarize, you must have excellent basic science in order to have excellent applied science; you can’t take shortcuts. It’s the importance of integrating different disciplines, people from different backgrounds, and the service to the community.

Rich Soll: Looking to the future, what milestones would you like the center to achieve in the next two years?

Ehud Gazit: I hope that we will have several leads related to both common diseases and rare diseases that are less explored. This is a very challenging type of opportunity, since we can’t count on  having a drug come from the center very soon, but if the number of researchers, faculty members,  and graduate students are involved in drug discovery opportunities was doubled or tripled, that would be very important. And I’d like to extend our dialogue with Israeli start-ups in the biomed industry, which needs the help of the academic institutes. Of course, we are truly hoping to get therapeutic leads for various diseases, but we also want to increase the community related to drug discovery both at the university and at the national level.

Rich Soll: So five years from now, what do you think the center would like?

Ehud Gazit: I hope the center, even though it’s still in its infancy, will be a source of excellence for the Tel Aviv University community as well as the community in Israel, and  maybe internationally. I hope that we could provide the scientific community with new paradigms for drug discovery with new methodologies on the development of drugs. I hope that in five years, drug discovery will be a strong point of Tel Aviv University.

Rich Soll: It’s a wonderful set of ambitions. What will it take to achieve these goals?

Ehud Gazit: I think the way to be successful is to be brave, to think big, and to think out-of-the-box. Scientific activity is twofold: on one hand it’s to be the best possible at the state-of-the-arts; you must think at the current state-of-the-art in science.  At the same time, you always have to challenge the known. You have to say, ‘maybe it’s different, maybe I can do it in a different way.’  I try to do this at the center; it is challenging.

Rich Soll: What advice would you give to young scientists?

Ehud Gazit: You must ask the major questions, you must be as good as possible at the science that you do, but you still have to think, ‘maybe I could change things, maybe I could use a different type of mechanism.’ Maybe it’s something beyond what we see. To be a successful scientist you must be brave. You have to believe in what you do. You shouldn’t be disappointed with failure. You should be very happy when you’re experiment is running just as opposite as what you expected.


Harnessing Science for the Most Neglected Diseases – A Chat with Charles Mowbray, Ph.D., Head of Drug Discovery, DNDi

By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx), December 01, 2016

“Some of these diseases are rapidly fatal, cause huge loss of life, and have a huge impact on people’s lives. Often these are diseases that have attracted little research and attention and certainly haven’t been the focus of traditional research and development because there’s no profitable market; nobody’s going to get rich from making drugs for neglected diseases.”

In 98 countries around the globe – mainly in Asia, East Africa, South America, and the Mediterranean region –350 million people are at risk of developing leishmaniasis, a potentially fatal disease that is caused by protozoan parasites transmitted through a female sand fly bite. Leishmaniasis, known as a neglected disease, affects the poorest of the poor and has strong links with malnutrition, low-quality housing, and lack of resources. Existing drugs for this disease have serious drawbacks in terms of safety, resistance, stability, and cost.

Developing countries continue to face significant morbidity and mortality rates from such neglected diseases  even though these diseases account for 11% of the global disease burden, of the 850 new therapeutic products approved between 2000 and 2011, only 4% were indicated for neglected diseases.

As head of drug discovery at Drugs for Neglected Diseases initiative (DNDi), Charles Mowbray is leading efforts to develop more effective treatments for neglected diseases such as leishmaniasis that are short course, oral, safe, effective, and low cost.DNDi, a collaborative patients’ needs-driven non-profit drug R&D organization launched in 2003, was set up by key research and health institutions from the public sector in neglected-disease-endemic countries – the Oswaldo Cruz Foundation from Brazil, the Indian Council of Medical Research, the Kenya Medical Research Institute, the Ministry of Health of Malaysia and France’s Institut-Pasteur, with seed funding from Médecins Sans Frontières (MSF)/Doctors Without Borders (MSF’s 1999 Nobel Peace Prize), and WHO–TDR (Special Programme for Research and Training in Tropical Diseases) as a permanent observer.

Mowbray  a trained medicinal chemist who spent 19 years at Pfizer Worldwide Research and Development  joined DNDi in 2011 and lends the organization his vast experience across disease areas, target classes, and medicinal chemistry strategies. He also has a keen understanding of global health issues, and developing innovative scientific, collaboration and fundraising approaches to deliver much-needed novel medicines to patients around the globe.

I recently spoke with Mowbray, who discussed DNDi’s successful combination of innovative science, unique R&D model, global partnerships, and strong advocacy, as well as what motivates him to go to work every day.

Rich Soll: Why did DNDi decide to focus on neglected diseases?

Charles Mowbray: The medical need and the burden are huge and there are very large numbers of people in large portions of the world affected by neglected diseases and neglected tropical diseases, so there’s an urgent need to do something about that. Some of these diseases are rapidly fatal, cause huge loss of life, and have a huge impact on people’s lives. When DNDi was created, we began working on malaria. It was one of the first organizations to put together artemisinin-based combination therapies. Then we added other neglected diseases to our portfolio: sleeping sickness, leishmaniasis, and Chagas disease, and later other parasitic infectious diseases, which had very poor existing treatments. Often, these are diseases that have attracted little research and attention and certainly haven’t been the focus of traditional research and development because there’s no profitable market; nobody’s going to get rich from making drugs for neglected diseases.

Rich Soll: What is DNDi’s role in helping to provide affordable medicines to those who do not have access to them?

Charles Mowbray: DNDi is not just an R&D organization. We think of ourselves as having three core missions. One is obviously the research and development piece, another is advocating for policy change, new models for sustainable research and development, and sustainable access. The third part is about building and strengthening capacity for R&D in the disease endemic countries. I think we are different than some of the other PDPs in that we have a larger mission, and we certainly advocate for new models because we recognize that the traditional pharmaceutical model is broken for these diseases, so we need more alternative approaches.

We’re currently operating some projects which are demonstration projects; we received some seed funding from the WHO and TDR to demonstrate some alternative approaches to research and development. We’re also bringing partners together, both public and private, to develop innovative ways of doing science. For example, we have a Neglected Tropical Diseases Drug Discovery Booster project where five pharmaceutical companies are working together on the same project with us to try to accelerate development of high throughput screening hits that could lead to more lead optimization projects. That’s a collaborative approach where companies are sharing a bit more information with us and even with each other, which is quite unusual.

Rich Soll: I counted about 33 projects in DNDi’s 2016 pipeline, which is very impressive. Can you give some examples from that pipeline and what your strategy has been?

Charles Mowbray: One major focus area is sleeping sickness. When DNDi got involved with first and second stage sleeping sickness, treatments were pretty horrible. We took two existing medicines that didn’t work very well and combined those and came up with a regimen that produced much better efficacy, was much better tolerated, and a step in the right direction. But it’s one of those drugs that requires an infusion, and getting large amounts of sterile water for infusion in remote parts of Africa where sleeping sickness is a problem isn’t easy. You need to build infrastructure, and you need transport to remote areas. So although the treatment is much better in terms of efficacy and safety, it’s far from convenient. We’ve been striving to come up with some simple oral therapies which could be distributed in a primary healthcare setting or even in a village setting with minimum requirement for infrastructure.

Now we are in the process of completing a Phase II/III trial for a sleeping sickness drug and we’re preparing submission for registration. It’s a short-course, 10-day therapy of an oral medicine. We have another candidate, which started its first Phase II/III studies, and we’re hoping this is going to be a single dose cure for stage 1 and stage 2 sleeping sickness, so in terms of a straightforward medicine that could be used in resource-poor settings, this would be fantastic.

Rich Soll: DNDi has made significant strides in developing new technologies as well. Can you give us an example?

Charles Mowbray: One example is that we got involved in pediatric HIV in 2011, recognizing that young children and babies weren’t well served with existing HIV medicine. Unfortunately, once every two minutes a baby is born HIV positive. It’s not an area where traditional pharma would be particularly interested in working. It’s an extremely difficult patient population to develop medicines for with lots of problems and risks for traditional pharma. These babies are growing up HIV positive, and so the treatments available to them are not adapted to kids, and a key drug in the preferred regimen tastes really awful. Previously it was only available as a syrup or a tablet. A tablet is no good for young kids. They also often live in countries where climates are extreme, so having limited shelf life stability is not convenient. So we’re working hard at coming up with properly adapted treatments. Our goal here is audacious – it’s a 4-in-1 combination therapy, a boosted protease inhibitor plus two nucleoside analogues, and a taste-masked formulation – something that mothers can sprinkle on the kids’ food and they get all four treatments and it doesn’t taste bad. We have also found that some of these kids are unfortunate to also be infected with TB and they’re on drugs for that, so they need a specific treatment to ensure there is no negative interaction between the HIV and the TB treatment, so we have developed a super boosted protease inhibitor treatment for them as well. These important things really make a difference. It’s been challenging, and I’m incredibly impressed by the progress that my colleagues have made in just a few years.

Rich Soll: Some of these neglected diseases have different stages. How do you deal with that?

Charles Mowbray: Leishmaniasis has different forms: visceral leishmaniasis, for example, is an acute and rapidly fatal disease if untreated. There’s also a cutaneous form of the disease where the parasites reside in the skin and produce very unpleasant, slow-to-heal lesions across people’s bodies. Sometimes those can become even more complicated, destroying the nose and face and around the joints. Unfortunately, now there are more and more patients infected with leishmaniasis who also have HIV, both diseases of the immune system, and they both make each other more difficult to treat. So understanding the needs of these patients and trying to work out how to optimize the current therapies means that we recognize that even within a particular disease there are even more extreme needs that we need to address.

Rich Soll: What is the status of some of DNDi’s treatments for leishmaniasis?

Charles Mowbray: We’ve already successfully produced some combination therapies, which are now in use; they are on the WHO’s Essential Medicines List (EML) and they are used in Africa and India. We’re also about to get a change in the recommendation in Latin America. Those are already making a difference for patients. The new compounds that are coming through are obviously in development; as you know it takes some years to complete the development and to get the compounds registered and then advocate for changes in national and regional policies for them to be recognized as first line or second line treatments.

We work with ministries of health, governments, and regional health organizations so we can anticipate and prepare the way to facilitate rapid registration and rapid adoption in multiple countries in order to get the treatments to patients as quickly as we can.

Rich Soll: Leishmaniasis and Chagas disease are part of DNDi’s Neglected Tropical Diseases (NTD) Drug Discovery Booster consortium. Can you tell us more about this collaborative effort?

Charles Mowbray: When DNDi was created, we could only screen a few compounds a month because they were really difficult assays to work on. By working with some of our partners some things have improved and now we have high content screening; we can actually screen against these intracellular parasites and test bigger libraries of compounds. Basically, we can mine our partners’ compound library for a range of neglected tropical diseases. Traditionally, early stage drug discovery is an expensive and time-consuming process. Our booster program uses a multilateral, simultaneous search process across participating companies, which allows us to access compounds generated over many decades of research. We’re about a year and a half into the program now and it’s been more effective than we ever dreamed it would be. We have five major pharmas working with us on this project, and people are really excited about it. It’s a different way of approaching drug discovery.

Rich Soll: It takes a unique breed of person to be doing this kind of work. How did DNDi assemble such a diverse group of people?

Charles Mowbray: We wanted a wide range of disciplines – pre-clinical scientists like myself, clinicians, real disease experts, especially for neglected diseases, advocates, fundraisers, communicators, operations people, and a finance team – all the different disciplines and skill sets that we need to make an organization like this work. We’re a very global organization as well – although we’re headquartered in Geneva, Switzerland we also have regional offices around the world. They can be involved in conducting clinical trials, fundraising, advocacy, research, and a whole range of activities – Latin America, Africa, India, Malaysia, Japan, and the U.S. Some come from a humanitarian background, many have worked with MSF or other organizations in the field, and they really understand the challenges of helping patients in some of the most difficult conditions and most remote areas. We also have people who have a long history of working with the pharmaceutical industry, and traditional for profit projects, and they bring in those skills and connections to help us. I would say they are all very passionate and very motivated.

Rich Soll: What is your proudest achievement at DNDi?

Charles Mowbray: The NTD booster program was my idea and I was fortunate enough to be given the opportunity and space to try to make that fly. To witness what we’ve been able to do in a relatively short amount of time is exciting. Another highlight for me was that earlier this year, we nominated a candidate for leishmaniasis; it’s a project I’ve been working on for some years. There’s a molecule that’s developing through the pre-clinical stage at the moment. In less than a couple of years that could be in human volunteers and then on to patients. We are focused on the best science for the most neglected diseases. I can’t think of a more motivating place to work.