Today, there are 7000 rare diseases affecting 250 millions people in Europe and only 5% have an approved treatment. Caroline is accelerating the cost-effective development of unexplored therapeutic opportunities in rare diseases by addressing key translational gaps and clinical development challenges. She is acting as an investor, a patient voice integrator and a trusted broker between patients, pharmaceutical companies, biomedical centers of expertise and regulatory authorities.
Caroline has created a new way forward for existing drugs to be developed in rare diseases. She is accelerating the cost-effective development of unexplored therapeutic opportunities in rare diseases by addressing key translational gaps and clinical development challenges, acting as an investor, a patient voice integrator and a trusted broker between patients, pharmaceutical companies biomedical centers of expertise and regulatory authorities.
The New Idea
In a health system that lacks incentives to drive the recycling of previously developed drugs for rare diseases, EspeRare serves as a none-commercially driven trusted broker to coordinate and drive the complicated process of drug development among the major actors: patient groups, regulatory bodies, clinical research partners and pharmaceutical companies. Through its unprecedented positioning, Esperare applies all the pieces of a comprehensive solution –R&D and project management expertise, patient-centricity, and hybrid financing mechanisms – to advance the discovery of new treatments for these underserved patients.
An important piece of this solution is the engagement of patients and the pharmaceutical industry. Under a system in which pharmaceutical companies rarely engage in drug repositioning for rare diseases – as it is considered resource intensive with low financial returns – Caroline provides commercial partners with an attractive and viable alternative. EspeRare incentivizes investments in drug repositioning by pooling additional financial resources from public funds, patient groups, as well as by reducing R&D costs, therefore de-risking the validation of these unexplored opportunities in rare diseases. It also offers pharmaceutical companies flexible business models that are adapted to a given asset and a given repositioning program.
Caroline’s approach to drug repositioning extends beyond its benefits to rare disease populations. Her repositioning approach can be replicated to other mainstream diseases as health systems are moving toward more personalized care approaches in smaller patient populations. She is also considering replicating her approach to other health domains, such as prevention and diagnostics which faces similar challenges to forge sustainable economic models and avoiding two-tiered medicine.
EspeRare is currently undergoing two repositioning programs and has 5-7 more under evaluation in its pipeline, that are set to be launch within the coming years. Not only will these programs accelerate the birth of new treatments for underserved patients, but they will also improve patients’ quality of life by providing guidance, support and enhance their disease understanding. At a more systematic scale, EspeRare’s model - with investment pooling and multi partnerships - is pushing the health sector to improve and cheapen development and access to health more broadly.
There are more than 7,000 different rare diseases in the world, that collectivity affecting around 250 million people. Given the fragmentation of patients, in Europe for example, only five percent of these diseases have approved therapeutic solutions. Under the current system, these patients are underserved by medicine and, with their families, they undergo a great deal of stress, anxiety and pain while waiting for an accurate diagnosis and treatments to be developed to address their medical needs. Repositioning of existing drugs offers opportunities to accelerate therapeutic development, since repositioned drugs have already passed a significant number of tests and can bypass much of the initial studies and R&D cost needed to bring a drug to the market. However, many barriers exist which prevent the mainstream use of drug repositioning approach for rare diseases.
The first is a structural lack of coordination among the actors in the repositioning process. Actors involved in developing drugs work in silos and do not have clear incentives to coordinate; for example, cooperation between academic biomedical groups and pharmaceutical companies is challenging due to misalignment of objectives and work practices.
Several well-intended efforts try to work on drug repositioning for rare diseases, but they face challenges. Patient groups engage in therapeutic development, but tend to focus on one particular rare disease instead of working across rare diseases, which can result in competition for resources. Biopharmaceutical companies engage in drug repositioning, but it is uncommon for them to focus on rare diseases because of low profit margins. Furthermore, their ability to engage with patient groups, a critical element for successful drug development, is limited by commercial conflicts of interests. Finally, several non-profits have emerged on the scene to fundraise and drive research for rare diseases. However, those organizations sometimes lack R&D hands-one expertise to drive all activities required to generate robust data packages. Their also often miss pharma know-how to directly integrate biopharmaceutical companies in the process to insure drug development continuity. Currently integration of commercial partners is, in most cases, an important step in giving the best chance to investigational drugs to reach patients as it is extremely challenging to cover the full cost of the entire repositioning process – from drug development, to clinical trials, to commercialization – without engagement of the private sector.
On the other hand, traditionally the pharmaceutical industry business model focuses mainly on developing blockbuster drugs that impact millions of people. Given the scarcity of patients in rare diseases it is challenging for these commercially-driven companies to develop attractive market opportunities in those diseases without commercializing drug at very high price. Furthermore one of the limiting factor for commercial entities to engage in the development of repositioning opportunities is that despite their potential high therapeutic value, repositioned drug cannot be commercialized at that premium price. To date, there was no operational and financial model that incentivized pharmaceutical companies to invest in the clinical testing and commercialization phases of drug repositioning opportunities for rare disease patients.
These challenges come with a counter opportunity. The pharmaceutical industry needs to think about new business models to drive sustainability. It is increasingly challenging for the industry to drive high returns on drug development and high profit margins. With a shift toward personalized medicine (notably based on scientific discoveries in genomics), the blockbuster model is no longer the only viable model. However, pharmaceutical companies are struggling to make the shift to new models alone, and more than ever needs access to agile and innovative partners that are able to bridge the efforts of patient groups, public biomedical institutes and regulatory bodies to adapt to more individualized ways of conducting drug development and healthcare for smaller patient populations.
Caroline, a mother to a child with a rare disease who spent seven years working in the pharmaceutical industry, recognized that a novel financial and operational model was needed to develop repositioning opportunities that often “sits on shelves” of pharmaceutical companies, thus give a chance to much-needed unexplored treatments to reach patients underserved by medicine.
Coming from the pharmaceutical sector, Caroline was able to identify the biggest barriers to biopharmaceutical companies investing in drug repositioning for rare diseases. The first was the high R&D cost and the second was the complex stakeholder process. EspeRare overcomes both by offering an attractive and viable commercial model for these companies to engage. She reduces the overall costs of the repositioning process by pooling additional investment resources (mainly public grants, patient group funds and pro-bono partnerships with the best experts possible). In most situations, pharmaceutical companies contribute about one quarter of the cost of what they would invest if they were working alone. EspeRare also makes the process of repositioning drug more efficient by diving stakeholder engagement and coordination of collaboration-intensive activities that requires agility and are complexes to manage for large pharmaceutical companies, such as working with patient organizations, academic center, key opinion leaders and regulatory authorities.
Caroline maintains patient-centricity above all in order to work across silos and include the patient voice at each step of the process. With patient groups, EspeRare identifies critical medical unmet needs and prioritize rare diseases of focus. She then uses a data mining process that integrates data on existing drugs and rare diseases pathophysiological processes to uncover unexplored repositioning opportunities. This data driven approach allows her to more systematically identify and evaluate repositioning opportunities with high therapeutic potential across a range of rare diseases.
Once repositioning opportunities are identified, EspeRare negotiates, with asset owners, rights to develop the existing drugs in the rare disease of interest. To further incentivize the deal making, EspeRare offers flexible partnership models, depending on whether the asset owner is looking to keep the exclusivity on the commercialization or concede the intellectual property to EspeRare. However independently of the business model that is favored, social and commercial win-win “guiding principles” are established between EspeRare and its biopharmaceutical partner to secure ethical development and affordable patient access to treatments.
The outcome of Caroline’s repositioning approach is to give a chance, accelerated and de-risked drug repositioning, which is not achievable with traditional approaches. It applies its drug development know-how to conduct preclinical and early clinical assessments of the therapeutic opportunities. EspeRare sits at the interface of the major actors (patient groups, regulatory bodies, clinical research partners) and use its in-house pharmaceutical R&D expertise, to drive all rang of development activities required to conduct a robust evaluation of the therapeutic potential of its programs. The key here is strategic coordination and constant engagement of patients and other key partners throughout the process. For example, EspeRare saves significant time and gains access to a trusted interaction with patient organization by tapping into Ashoka Fellow Sharon Terry’s network of 1,500 patient groups, which is a huge lever to integrate the patient voice and access to data and patient samples at the very onset of drug development activities. A second outcome is guiding and accompanying patients as trusted allies during these often complicated and difficult phases. For example in those diseases where the lack of biomedical knowledge if often a critical barrier to therapeutic development, Caroline is supporting the development of key components of this “drug development infrastructure” such as clinical end-points, natural history data, prevalence information, ect…
EspeRare is currently working on its first two ongoing programs, the first being the development of Rimeporide, a drug (developed by Merck for heart failure and abandoned in Phase I trials), which EspeRare is currently repositioning in Duchenne Muscular dystrophy, a deadly pediatric myopathy for which no appropriate treatment currently exists. EspeRare has also initiated a second repositioning program in a rare renal disease; with a UK biomedical center expert in that disease, together they have initiate research activities to demonstrate that a drug, originally developed in a brain cancer until Phase III trials, has a potential to treat patient affected by his debilitating renal disease.
Caroline’s strategy to engage future companies is to look for those internal champions that see the longer-term vision and the opportunity in drug repositioning for rare diseases. She is engaging those business leaders that recognize the opportunity to evolve R&D and drug development for personalized medicine. Already, Caroline has found these champions in Merck Serono and she is currently exploring other pharmaceutical partnerships as well.
Finally, Caroline is thinking beyond rare disease treatment. She sees rare diseases as the best case study to explore new models for health personalization challenges. By developing innovative strategies for rare diseases, EspeRare aims to open a new path to affordable drugs and better healthcare as a whole. Her approach involves: a) implication in the of policies that will prevent two-tiered medicine, for instance within working groups in Brussels; and b) broadening her scope of research to non-rare disease repositioning opportunities, for instance to treat a specific subpopulation of autistic children.
Caroline comes from a family of artists and scientists that knows what it is to start from scratch: her parents left everything behind in the Czech Republic prior to immigrating in Switzerland. Caroline has also experienced relocation across continents when she left Switzerland to move to California, and then returned to Switzerland with her daughter to start new studies. These cross-continental experiences led her to constantly challenge herself and break out of her comfort zone to rebuild her life. She is a very determined and relentless person with a strong ability to push forward into the unknown.
From a young age, Caroline was engaged in many types of activities across many disciplines, from science to arts, athletic competitions to fashion. She studied in Geneva and in California and holds degrees in molecular biology, design and product development. After her studies, she participated in the launch of a software company in the Silicon Valley, while leading the rebranding of several fashion labels. Her cross-disciplinary approach and experiences in many domains, especially in science, give her a unique ability to think broadly in an innovative and structured way.
Before founding EspeRare, Caroline served six years in leadership roles building the R&D Knowledge Management department at the pharmaceutical company Merck Serono. While not an expert on the topic, she was recruited by her boss because of her combined innovative and analytical skills. She headed a department of PhD scientists and became a high performer (top 1%) within this more the 14’000 employee company. This is where Caroline developed her pharmaceutical expertise and data mining approach to drug development, which she now applies within EspeRare. Thanks to her experience in the pharmaceutical world, she is equipped to interact with big companies and in that context has been successful in coming up with appealing incentives and creating win-win partnering scenarios. She brings to EspeRare broad know-how and international expertise in translational research, public-private partnerships, and product development within the pharmaceutical and information technology industries.
Her more than 10 years battle to find a diagnosis and the best care for her child affected by an uncharacterized rare disease has triggered a profound change in Caroline’s life. Caroline quickly came to understand that the lack of knowledge about rare diseases and the difficulty for patients to be understood and receive adequate support was due to the lack of coordination between health players and the lack of means for incorporating the patients’ voice in the drug development process. She also witnessed the need to channel and translate patients’ engagement towards better health outcomes for sick children. Today, the medical community is still unable to diagnose her daughter’s disease precisely, but it has given a new purpose to Caroline’s personal and professional life itinerary: bringing drugs to underserved patients at affordable costs and improving their lives. Through the EspeRare Foundation, she has created an innovative approach to identifying and developing compounds that have a therapeutic potential in rare diseases.
In 2011, Caroline encountered US Ashoka Fellow Sharon Terry. Through Sharon’s mentorship, patient-centricity became an essential building block in the EspeRare model to make patients key partners and players in the research and development process. In 2012, Caroline successfully received an initial funding of €2.8 million from Merck Serono through its Entrepreneur Partnership Program to explore drug repositioning for rare diseases. In addition, Merck Serono transferred the rights to Rimeporide to Esperare, a compound initially developed for heart failure and that is now being repositioned for Duchenne Muscular Dystrophy (DMD), a lethal genetic rare disease affecting one in every 3,600 males.
Caroline could have set up EspeRare as a for-profit organization, with great potential for cash return, or found very attractive jobs in other pharmaceutical companies, but she deliberately opted for a non-profit positioning so that she can engage directly with patients and drive treatments affordability and better patient access to medicine. This model will allow her to follow her vision, which goes far beyond EspeRare and rare diseases, to evolving the drug development model and creating access to treatment for all.