ANNUAL REPORT 2015 Mission & vision
MISSION VISION At EspeRare, we address the translational A world in which patient engagement, gap in paediatric rare diseases by uncovering good science, pharmaceutical excellence the potential of existing therapeutic inter- and health authorities come together to ad- ventions to tackle unmet life-threatening dress the medical needs of children affected medical needs. by rare diseases, ultimately alleviating the healthcare burden of their conditions. $VDQRQSURĆWZHDFKLHYHWKLVWKURXJKD collaborative approach centred on patient engagement with the aim of giving people universal access to these therapies.
Picture of EspeRare founders : Florence Porte-Thomé, Caroline Kant-Mareda & Béatrice Greco
2 EspeRare | Annual Report 2015 Message from the President 4 2015 highlights 6 Addressing rare diseases 8 Advancing rare disease treatments 10 The translational gap, a major roadblock for new treatments 12 Building our portfolio 14 First programme: Rimeporide in Duchenne Muscular Dystrophy 16 Second programme: Cilengitide in Focal Segmental Glomerulosclerosis 18 Organisation 20
Financial View 26
How you can support EspeRare 34
Established in Switzerland in 2013, EspeRareLVDQHZQRQSURĆWIRXQGDWLRQZLWKJOREDO reach, focused on accelerating the development of treatments for underserved patients affected with rare diseases.
EspeRare | Annual Report 2015 3 Message from the President
The EspeRare foundation was launched at the International Rare 'LVHDVHV 5HVHDUFK &RQVRUWLXP ĆUVW Congress in Dublin in April 2013. Our goal is to pioneer a collaborative model that accelerates and de-risks the devel- opment of treatments for underserved patients affected by rare diseases. Our Product Development Partnership model for rare diseases is a unique QRQSURĆW EXVLQHVV PRGHO WKDW EULQJV together public, private, academic and philanthropic sectors to develop unex- plored or sleeved treatments for debili- tating rare diseases.
4 EspeRare | Annual Report 2015 “ If opportunity doesn’t knock, build a door.” Milton Berle
Dear Friends,
It is hard to believe, but EspeRare is three We are very excited to have reached a point As we have validated the relevance of our years old! In this short time, we have only where we have validated the relevance novel model, we are now shifting into an felt a strong increase in interest and need RI RXU XQLTXH PRGHO ZLWK RXU ĆUVW 5 ' expansion phase. We are scaling up with the for the niche in which we have placed programme: the rescue of Rimeporide, development of a portfolio of therapeutic our efforts. While there is a tsunami of a drug that was left abandoned by a programmes in multiple rare diseases. interest in rare diseases, and even in drug pharmaceutical company and for which we As part of a longstanding partnership repurposing, all of the other activities KDYH REWDLQHG 2USKDQ 'UXJ 'HVLJQDWLRQ with Ashoka, McKinsey has worked with DUH LQ WKH IRUSURĆW VSDFH 2XU PLVVLRQ LV this year in Duchenne muscular dystrophy. Caroline and her team to enhance the comprehensive: not only do we want to Thanks to our highly collaborative and delivery of our unique approach and repurpose existing drugs for rare conditions, philanthropic model, not only have we given maximise our impact for the patients we but we are also concerned that access a chance to this drug to reach those children serve. To this end, McKinsey supported us to these drugs is fair and equitable. We in need by combine public, philanthropic in thinking through our business model and are concerned that current trends in rare and private funding but we are proud to GHĆQLQJRXUJURZWKSULRULWLHV diseases show astronomical prices being set report that we are now investigating this and accepted by some markets around the drug in boys affected by Duchenne in four Personally, as I work in the rare disease world. The EspeRare model was developed European clinical reference centres. world, particularly in a leadership role in as an alternative to this costly approach that organisations such as the International is starting to burden health economics and EspeRare has received important Rare Disease Research Consortium and the creating access to medicine challenges. recognition in this past year. Caroline Accelerating Medicines Partnership, I know .DQW RXU &(2 ZDV QDPHG 6ZLVV :RPDQ there is a need for EspeRare because it can We are convinced that accelerating the Entrepreneur of the Year. This recognition, implement the model that great strategists process of moving molecules that have from the Club of Female Entrepreneur, are formulating. We look forward to undergone initial development into another recognizes her tremendous vision in stronger and more energetic collaborations indication is a critical and less risky path to JLYLQJ ELUWK WR D QRQSURĆW RUJDQLVDWLRQ WR with donors, partners, and patients in the alleviating the burden of these diseases. repurpose interventions, decreasing the coming year. They are rare, and affect only small enormous amount of time and money it populations, but taken collectively they generally takes to alleviate the suffering Sincerely, represent a major healthcare burden as they of individuals affected by rare diseases. affect more than 1 in 10 people worldwide. The Swiss economic journal Bilan also Sharon Terry recognised EspeRare as a top 8 Swiss start President up for 2015.
EspeRare | Annual Report 2015 5 2015 highlights
JAN-FEB MAY 2015 2015
EspeRare selected as a Top Swiss start-up The Rimeporide drug receives the Orphan with an innovative business model Drug Designation in Duchenne Muscular Dystrophy (DMD) Featured by the economic journal Bilan in January for its innovative business model, EspeRare is also The European Medicines Agency has granted the presented in the magazine edition of February in the 2USKDQ 'UXJ 'HVLJQDWLRQ WR 5LPHSRULGH IRU '0' top 8 Swiss start-ups, among 50 promising start-ups a life-threatening muscle disease affecting boys early in from all industries in which one should invest. Q childhood. This designation is a key recognition of the therapeutic potential of EspeRare’s leading drug under development, which is currently being tested in boy’s affected by this devastating disease. Q
JULY AUGUST 2015 2015
EspeRare part of a strategic task force to AFM-Téléthon renews its support to address rare diseases EspeRare’s therapeutic development efforts for Duchenne To reach its objective to diagnose most rare diseases DQG WR ĆQG QHZ WUHDWPHQWV IRU UDUH GLVHDVHV The French leading patient organisation has renewed by 2020, the International Rare Diseases Research LWV ĆQDQFLDO VXSSRUW WR (VSH5DUHèV SURJUDPPH LQ Consortium (IRDiRC) created a data mining and 'XFKHQQH 7KLV JUDQW LV FRĆQDQFLQJ FOLQLFDO WULDO repurposing task force to enhance collaborations activities currently being initiated in several hospitals and exploit tools to accelerate the development of in Europe. The AFM has also invited the Rimeporide QHZ WUHDWPHQWV 7KH IRXQGDWLRQèV &(2 ZDV LQYLWHG programme into its strategic portfolio, which gives to become a member of this group and provide her access to AFM’s network of biomedical experts to H[SHUWLVHDQGH[SHULHQFHLQWKLVĆHOGQ best advance Rimeporide for boys burdened by such debilitating disease. Q
6 EspeRare | Annual Report 2015 “ The voyage of discovery is not in seeking new landscapes but in having new eyes.” Marcel Proust
SEPTEMBER OCTOBER 2015 2015
CFE Swiss Woman Entrepreneur Award Rimeporide in Duchenne presented at granted to EspeRare’s CEO the 20th WMS Congress
This award highlights the exceptional entrepreneurial EspeRare actively participated in the 20th work of a business woman in Switzerland. By winning International World Muscle Society Congress this price, Caroline Kant gains a strong recognition for in Brighton (UK) with a poster presenting the her efforts in driving forwards the novel business model rimeporide compound and its possible applications in of EspeRare. “I am very proud that a mission-driven Duchenne Muscular Dystrophy. Q business was chosen for this year’s award, this shows that in today’s economy, social entrepreneurship is starting to JDLQLPSDFWUHFRJQLWLRQëFRPPHQWHG(VSH5DUHèV&(2Q
DECEMBER DECEMBER 2015 2015
McKinsey supports the foundation (VSH5DUHEHFRPHVD6,%DIĆOLDWH enhancing its impact for patients 7KH 6ZLVV ,QVWLWXWH RI %LRLQIRUPDWLFV LV D QRQSURĆW McKinsey supported EspeRare to think through coalition of over 60 bioinformatics research and service LWV EXVLQHVV PRGHO E\ GHĆQLQJ LWV LQQRYDWLYH YDOXH groups in Switzerland. EspeRare has been invited to proposition and growth priorities. As part of a MRLQ WKLV QHWZRUN DV DQ DIĆOLDWHG LQVWLWXWLRQ :LWK WKLV longstanding partnership with Ashoka, McKinsey partnership, the foundation will be able to collaborate has worked with Esperare to enhance the delivery and leverage world-class bioinformatics collaborations of its highly distinctive approach and to maximize its and infrastructure that will support the development of impact for patients. Q its drug repositioning platform for rare diseases. Q
EspeRare | Annual Report 2015 7 Addressing rare diseases
WHAT IS A RARE DISEASE? EMPOWERED ADVOCACY ORGANISATIONS IN RARE DISEASES In Europe, any disease affecting less than Particularly in rare conditions, disease 1 person in 2000 is considered rare. In the advocacy organisations are key part- 86DGLVHDVHRUGLVRUGHULVGHĆQHGDVUDUH ners at each stage of drug development: when it affects less than 200,000 people in the US.1 ÆGiven the scarcity and fragmentation of medical expertise, patients are highly Rare diseases are chronic, progressive, knowledgeable and have a strong degenerative and often life-threatening. LQćXHQFHRQGUXJGHYHORSPHQW Because of their low prevalence and their high level of complexity, they need special ÆThrough support, research, fundraising combined efforts for their management. and lobbying, they actively develop expert networks, manage disease related knowledge and engage in and support biomedical research.
1 Source: Orphanet and the US Orphan Drug Act
8 EspeRare | Annual Report 2015 PATIENTS ARE AT THE CORE OF CURRENT PROGRESS IN RARE DISEASES: Individuals affected by rare diseases, drug development process. EspeRare foundation’s strategic alliance with their families, communities and advocacy is exceptionally well positioned to gain Genetic Alliance, a network of more than organisations have increasingly been from the great leverage of ‘patient 1200 disease advocacy organisations. recognised as critical partners in the centricity’, in particular because of the
RARE DISEASES: A MAJOR GAP IN THE MEDICAL LANDSCAPE AFFECTING CHILDREN
people affected 1 out of 10 in Europe affecting 50% children
9 years on average the is required diagnosis for a correct Odyssey diagnosis:
7000+ chronic rare diseases Only 5% of diseases with approved therapeutic solutions
For each programme, we strive to develop trusted collaborations with patient organisations, to truly deliver patients-centred drug development.
EspeRare | Annual Report 2015 9 Addressing rare diseases Addressing rare Advancing rare disease treaments
RARES DISEASES: A MAJOR GAP IN THE MEDICAL LANDSCAPE AFFECTING CHILDREN
DRUG DEVELOPMENT, A LONG, INSUFFICIENT COORDINATED COMPLEX AND COSTLY PROCESS EFFORTS IN DRUG DEVELOPMENT Why do only 5% FOR RARE DISEASES of rare diseases Developing new treatments is expensive, have approved time-consuming and requires strong coor- 'HVSLWH VLJQLĆFDQW SURJUHVV LQ VFLHQWLĆF treatments? dination between a large spectrum of re- research and technologies, drug develop- search and development (R&D) activities ment remains inadequate to address criti- and expertise. Recent reports estimated an FDOPHGLFDOQHHGVLQUDUHGLVHDVHV2QRQH DYHUDJHH[SHQGLWXUHRIDWOHDVWRQHELOOLRQb hand, therapeutic development is suffering DQGDWLPHIUDPHRIWHQWRĆIWHHQ\HDUVWR from the heterogeneity and complexity bring a drug to the market. Unfortunately, of these diseases, the limited number of increased spending on drug R&D did not patients, the fragmentation of medical ex- lead to an increase in the number of drugs pertise and the lack of pathophysiological approvals. XQGHUVWDQGLQJ 2Q WKH RWKHU KDQG SKDU- maceutical companies are often reluctant to invest in these diseases for which com- PHUFLDO SURĆW ZLOO EH OLPLWHG GXH WR WKH small market size.
ESPERARE DISEASE FOCUS
EspeRare opted to concentrate most of its activities in rare paediatric diseases that represent nearly 50% of rare diseases. Furthermore given that EspeRare cannot develop the knowledge and the network of experts required in thousands of dis- eases, the foundation has selected around WKLUW\GLVHDVHVRQZKLFKLWĆUVWIRFXVHVLWV efforts. These diseases have been selected based on multiple criteria’s, ranging from the severity of the unmet medical need, the foundation’s access to a strong disease community and the presence of a ripe “drug GHYHORSPHQWLQIUDVWUXFWXUHë HJVFLHQWLĆF knowledge, patient registries, diagnostic tests, etc.). Q
10 EspeRare | Annual Report 2015 ESPERARE RESCUES AND REPOSITIONS EXISTING DRUGS TO ACCELERATE THE DEVELOPMENT OF TREATMENTS FOR RARE DISEASES
Developing existing or abandoned drugs for However, repositioned drugs cannot be By repositioning or rescuing drugs, novel diseases offers an accelerated and de- commercialised at high prices as compared EspeRare accelerates the development, risked way of developing new treatments. to de novo therapeutics. Thus, so far, de- reduces costs, and increases chances of spite these clear therapeutic appeals for success for patients to access new medi- There are some inherent incentives to this patients, the approach has never become a cines. The foundation model allows the approach: strategic focus for biopharmaceutical com- development of drug repositioning op- panies, leaving many of these opportunities portunities that remains economically ÆExisting drugs are already known to to treat rare diseases unexplored. attractive for commercial partners and exert a biological response in humans EHQHĆFLDO IRU SDWLHQWV DQG WKH KHDOWK- and this response may become Focused on these untapped and care system at large. Q EHQHĆFLDOIRURWKHUKHDOWKFRQGLWLRQV de-risked opportunities, EspeRare LGHQWLĆHV DQG GHYHORSV H[LVWLQJ WKHUD- ÆMany steps in the drug development peutic interventions that offers impor- process such as drug bioactivity and tant prospects to improve the lives of JRRGVDIHW\SURĆOHLQKXPDQVKDYH patients with rare diseases. already been demonstrated during the initial development of the drug.
THE REPOSITIONING OF EXISTING DRUGS: A DE-RISKED & COST-CONTAINED APPROACH TO DRUG DEVELOPMENT
Novel drug Drug repositioning development for rare diseases
Average cost: $1 billion Average cost: 60% of usual drug development cost** Time to reach15 years the market: Time to reach the market:
Chances to reach patients 3-7 years (from phase I): 10%** +30% chances to reach patients High failure rate due to safety * Ref: Anne Pariser, LVVXHV DQGRUORZEHQHĆW for patients (48%)** 50% of FDA approved drugs Director at CDER in rare diseases are ** Ref: M. Hay et al., repositioned* Nature Biotechnology 32, 40–51 (2014) c
EspeRare’s strategy for rare disease drug development:
ÆFaster, de-risked and cost ÆBrings more affordable contained approach to drug treatments & access to medicine development* to rare disease patients
EspeRare | Annual Report 2015 11 Addressing rare diseases Addressing rare The translational gap, a major roadblock for new treatments
ESPERARE FOCUSES ON ADDRESSING THE “VALLEY OF DEATH” IN TRANSLATIONAL RESEARCH
The translational gap is the major roadblock ÆIntegrate «Patient voice» through 2QFHSURRIRIFRQFHSWLQKXPDQVLVGHPRQ- for new treatments to reach rare diseases alliance with patient advocacy groups strated and a conclusive data package gen- patients. This transition requires the erated, programmes can either go back to ability to translate research efforts often ÆMobilise research and clinical experts the originator or be transferred to indus- conducted in academia into robust drug and biomedical centres of excellence try partners who will have the necessary development activities traditionally to conduct preclinical and clinical capacity to drive later stage clinical trials, managed by the biopharmaceutical development activities registration and commercialisation. companies. ÆEthically engage industry partners At this point, to secure the integrity of pro- Using its collaborative approach and solid to manage transition into late clinical grammes, EspeRare agrees with commercial LQGXVWULDO GUXJ GHYHORSPHQW H[SHUWLVH development and commercialisation partners on ‘guiding principles’ for drug de- the foundation coordinates all necessary velopment, marketing and access to health, R&D activities to address this gap. ÆInteract directly with regulatory thus safeguarding the ethical principles of agencies and health authorities to best a drug initially developed within a philan- 0RUH VSHFLĆFDOO\ (VSH5DUH IRFXVHV RQ prepare path to approval and patient thropic structure. driving preclinical and early clinical deve- access to treatment lopment activities that are required to demonstrate human proof of concept of investigational drugs. For each of its drug development programmes the foundation Available develops Product Development Partner- Resources in Drug ships that: Development AvailableAvailable ResourceResourcess iinn RResearchesearch
Esperare FoundationFoundation
T
r a h n t s a la e D ti f on o al Valley
Understand Ideas Hypothesis Plausible Evidence Launch a new a Rare assumption for significant treatment Disease therapeutic value Efforts driven Preclinical / Early Clinical Efforts driven by academia by biopharma
12 EspeRare | Annual Report 2015 ESPERARE’S IMPACT: BRINGING TOGETHER PATIENTS AND COMMERCIAL INTEREST TO ADDRESS RARE DISEASES
Patient
Organisations Biomedical centers of expertise
De-risked EspeRare & Patient organizations Treatment & validated with better program patient Industrial full development & access commercialization EspeRare QRQSURĆWGUXJ development engine
m Program Deal 1 o l A pool of r a f with Pharma c unexplored s i n i therapeutic m l a opportunities ProgramP Deal 2 r C g o with Academia o t r l p a g ic in n v li ri c D re P Hybrid funding
Several therapeutic opportunities to treat (VSH5DUHèV QRQSURĆW GUXJ GHYHORSPHQW The advantage of the foundation lies in rare disease patients exist. However they PRGHOKDVEHHQGHYHORSHGWRVFLHQWLĆFDOO\ its unique ability to build a viable mod- remain forgotten on the shelves of phar- DQGĆQDQFLDOO\HQDEOHWKHHDUO\H[SORUDWLRQ HO DOORZLQJ XQH[SORUHG WUHDWPHQW WR EH maceutical companies or universities. of these opportunities. developed. It applies all the pieces of a These opportunities are never tested nor comprehensive solution: pharmaceutical developed because on one hand, biophar- ,QFUHDVLQJ ĆQDQFLDO SUHVVXUH RQ WKH 5 'DQGSURMHFWPDQDJHPHQWH[SHUWLVH maceutical companies are rarely willing to healthcare system and on treatment pric- SDWLHQW FHQWULFLW\ DQG K\EULG ĆQDQFLQJ risk investing R&D budget in small markets ing is calling for a new R&D model that mechanisms to reduce R&D costs and ZLWK ORZ SRWHQWLDO RI ĆQDQFLDO UHWXUQ 2Q can develop affordable drugs. timelines. EspeRare bridges patient and the other hand, academia often lacks the At the heart of EspeRare’s novel mod- commercial interests into a system that know-how to conduct robust drug devel- el lays the development of highly net- accelerate and de-risk drug development opment especially in late phases of clinical worked, patient-centred, public-private with the goal of bringing affordable new development. partnerships that drive the development treatments to rare disease underserved of affordable drugs for rare diseases. patients. Q
EspeRare | Annual Report 2015 13 Building our portfolio
Building our portfolio
:LWKLWVĆUVWSURJUDPPHLQ'XFKHQQHPXV- re-launch an existing therapeutic device for cular dystrophy, EspeRare has proven its infants affected by severe cardiac defects. ability to give a chance to dormant the- rapeutic opportunities. After two and EspeRare is looking to diversify its partners a half years, the foundation has now and develop its portfolio in rare diseases by: demonstrated the therapeutic poten- tial of Rimeporide, a shelved drug that ÆWorking with pharmaceutical companies, EspeRare is now developing in children patient organisations and academic affected by this debilitating disease. This SDUWQHUVWRLGHQWLI\RSSRUWXQLWLHVWKDWĆW ĆUVW SURJUDPPH LV DOVR D YDOLGDWLRQ RI WKH EspeRare’s development model and high strength of EspeRare’s philanthropic model unmet medical need disease scope to drive and fund drug development in rare diseases (see pages 12-13, 16-17). ÆEvaluating proposals from academic and biopharmaceutical companies to develop %H\RQG WKLV ĆUVW SURJUDPPH WKH IRXQ- their existing therapeutic assets GDWLRQLVEXLOGLQJDUREXVWDQGGLYHUVLĆHG portfolio of programmes that has the po- ÆDeveloping the Drug Repositioning tential to address critical unmet medical Platform, a biomedical informatics needs of children affected by rare diseases. HQJLQHWKDWV\VWHPDWLFDOO\LGHQWLĆHV Towards this goal EspeRare is developing and evaluates drug rescue and another existing treatment in a rare renal repositioning opportunities disease (see page 18-19) and is looking to
A PROGRAMME PORTFOLIO DUCHENNE MYOPATHY UNDER PROGRAMME DEVELOPMENT WITH MULTIPLE FOCAL SEGMENTAL PARTNERS GLOMERULOSCLEROSIS
Preclinical phase PEDIATRIC FORMULATION Clinical phase PROGRAMME
2QWKHPDUNHW DEVICE FOR CONGENITAL HEART DEFECT (AREADY MARKET APPROVED)*
SCOUTING FOR NEW OPPORTUNITIES
* EspeRare is looking to support the production and distribution of an already market approved device.
14 EspeRare | Annual Report 2015 ESPERARE’S PROPRIETY PLATFORM FOR THE IDENTIFICATION OF DRUGS TO BE RESCUED OR REPOSITIONNED IN RARE DISEASES
0101010101010010010101010100101010101001101001010010111010 1010001000010101010101001001010101010010101010100110100101001001010101010 00101110101010001000010101010101001001010101010010101010100000101010101010010010101 An “in silico” approach enables EspeRare to By combining wise selection of existing 01101001010010111010101000100001010101010100100101010101001110101010001000010101010101001 1010101010011010010100101110101010001000010101010101001001101001010010111010101000100001010101 discover novel therapeutic opportunities de-risked drugs within its Treatment data- 0101010100101010101001101001010010111010101000100001010101101010101001101001010010111010101000100010011 0101 0101010010100101110101010001000010101010101001001010101010101001011101010100010000101010101010010010101010 00010000101010101 01010101010011010010100101110101010001000010101010101001001010011010010100101110101010001000010101010101101001 1110101010001000 for existing drugs. EspeRare is currently EDVHDQGLGHQWLĆFDWLRQRIQHZGLVHDVHDS- 1010101010010101010100110100101001011101010100010000101010101001010101010011010010100101110101010001000010100110 01010010111010 10101001001010101010010101010100110100101001011101010100010010010101010100101010101001101001010010111010101001010101 10011010010 000010101010101001001010101010010101010100110100101001011110101010101001001010101010010101010100110100101001010101010100 010101 developing a proprietary computational plications using the Rare disease analytics 01010100010000101010101010010010101010100101010101001101001010001000010101010101001001010101010010101010100110101001001010 101001011101010100010000101010101010010010101010100101010100101110101010001000010101010101001001010101010010101001 10101010100 Drug Repositioning platform to system- system, our Drug Repositioning platform 010011010010100101110101010001000010101010101001001010101000110100101001011101010100010000101010101010010010101011010100 000010101 100101010101001101001010010111010101000100001010101010100101010101010011010010100101110101010001000010101010101001010100101110 01010001 001010101010010101010100110100101001011101010100010000101010101010100101010101001101001010010111010101000100001010101001101001010 101110 atise the discovery of such opportunities enables EspeRare to rescue drugs or to 101010001010010100101110101010001000010101010101001001010101010001010010100101110101010001000010101010101001001010110111 01010 0101001010101010011010010100101110101010001000010101010101101001010101010011010010100101110101010001000010101010101101001010010111010 0100 001001010101010010101010100110100101001011101010100010000101001010101010010101010100110100101001011101010100010000110101 00101 that includes the: uncover repositioning opportunities with 010101010100100101010101001010101010011010010100101110101001010101001001010101010010101010100110100101001011101010101010010101010 001101 100010000101010101010010010101010100101010101001101001010000100001010101010100100101010101001010101010011010010100100100101010 1001010 strong therapeutic potential for rare dis- 10111010101000100001010101010100100101010101001010101010011110101010001000010101010101001001010101010010101010100101010101 1001010 101001010010111010101000100001010101010100100101010101001000101001011101010100010000101010101010010010101010100101000010101 10 10101010011010010100101110101010001000010101010101001001010101001101001010010111010101000100001010101010100100101010100010 1. Treatment database: compiling data eases. 01010100101010101001101001010010111010101000100001010101010100101010101001101001010010111010101000100001010101010010 010111010 01001001010101010010101010100110100101001011101010100010000010101010100101010101001101001010010111010101000110101010 11010010100 0101010101010100101001011101010100010000101010101010010010010101010010100101110101010001000010101010101001001011 010101000100001 on 2,000 existing drugs with the po- 10101010010101010100110100101001011101010100010000101010100010101010100110100101001011101010100010000101001101 0101001011101010 1010010010101010100101010101001101001010010111010101000100101010101001010101010011010010100101110101001010 01010011010010100 0010101010101001001010101010010101010100110100101001011101101001001010101010010101010100110100101010101 1001 tential to be «re-developed» in rare di- $ ĆUVW YHUVLRQ RI WKH 'UXJ 5HSRVLWLRQLQJ 0101000100001010101010100100101010101001010101010011010010101010101010010010101010100101010101010 01 10010111010101000100001010101010100100101010101001010101010001000010101010101001001010101 seases. This database structures infor- platform was launched in March 2014. 00110100101001011101010100010000101010101010010010101010101010101000100001010101010 01010101010011010010100101110101010001000010101010101001000101110101010001 1010101010010101010100110100101001011101010100010000101010 mation about these drugs such as their The capability of the platform is being en- 1010100100101010101001010101010011010010100101110101010001 000010101010100010010101 initial disease(s) of development, their hanced and other data sources are being VDIHW\ DQG WR[LFLW\ SURĆOH DQG WKHLU integrated. biological mechanism of action. A colla- boration with the National Institute of EspeRare is grateful to the Loterie Suisse Health (US) is providing access to data Romande that has awarded the founda- on drugs developed worldwide. WLRQDJUDQWWRĆQDQFHWKH,7LQIUDVWUXF- ture of the Drug Repositioning platform. 2. Rare disease analytics system: inte- EspeRare is now looking for additional grating biomedical data on the mole- HQGRZPHQWV WR ĆQDQFH WKH SODWIRUP cular pathophysiology of its 30 targe- enhancement. Q ted rare diseases. The information is H[WUDFWHGIURPVFLHQWLĆFOLWHUDWXUHDQG specialised databases. This understan- ding of the biological cascades involved in these diseases is validated and en- hanced by biomedical experts in Espe- Rare’s network.
GAUGERX, A COLLABORATIVE PROJECT WITH GENETIC ALLIANCE GaugeRx is an open access, interactive, ecosystem in their disease. GaugeRx web-based tool under development, enriches the EspeRare’s Drug integrating and translating available Repositioning platform by integrating VFLHQWLĆFNQRZOHGJHRQUDUHGLVHDVHV multidisciplinary information for drug to support drug development. It also development to better assess potential aims to assist advocacy organisations in different rare diseases. in strengthening the drug development
EspeRare | Annual Report 2015 15 Building our portfolio
First programme: Rimeporide in Duchenne Muscular Dystrophy (DMD)
ABOUT DUCHENNE MUSCULAR DYSTROPHY (DMD)
Duchenne Muscular Dystrophy (DMD) is a other areas. Later in the twenties, this pro- effects upon chronic use such as increased severe genetic paediatric disease that gresses to complete paralysis and increas- risks for diabetes, fractures, oedema and affects 1 in 3,500 boys worldwide. LQJGLIĆFXOW\LQEUHDWKLQJGXHWRUHVSLUDWRU\ respiratory infections. While additional muscle dysfunction requiring ventilator therapies and treatments exist to alleviate Patients affected by DMD have progres- support as well as cardiac muscle dysfunc- symptoms, they do not alter the ultimate sive loss of muscle function and weakness tion leading to heart failure. Currently, outcome of the disease. in their early childhood. This progressive there is unfortunately no cure for this dis- There is still a critical need for new thera- PXVFOHZDVWLQJW\SLFDOO\OHDGVĆUVWWRORVV ease. The use of corticosteroid is the main pies to halt the progression of the disease of ambulation around 10 years of age. It pharmacological intervention, but it has and in particular the life-threatening cardi- eventually spreads to the arms, neck and OLPLWHG HIĆFDF\ DQG LQGXFHV VHYHUH VLGH omyopathy for all Duchenne boys. Q
“ Non-clinical data sug- gest that Rimeporide has DVLJQLĆFDQWSRWHQWLDOWR be a successful pharma- cological intervention to address cardiac and respiratory dysfunction observed in DMD.”
Prof. Francesco Muntoni, Chair of Paediatric Neurology, University College of London
Normal biceps Muscular distrophy
16 EspeRare | Annual Report 2015 Rimeporide is a safe, potent and selective NHE- 1 inhibitor. Rimeporide represents a novel investigational treatment It has been developed by Merck Serono for congestive that has the potential to delay the long term accumulation heart failure but was discontinued during phase I for of muscle degeneration and cardiomyopathy in DMD. strategic reasons.
BACKGROUND RIMEPORIDE IDENTITY CARD: 2013 “ Rimeporide has the EspeRare obtained the rights to develop potential to transform Name: Rimeporide Target: Sodium-Proton (Na+/ Rimeporide in neuromuscular diseases. Duchenne from a life H+) Exchanger (NHE-1) threatening to a chronic inhibitor 2014 disease” Originator: Merck Serono Two non-clinical studies demonstrated Original indications: 5LPHSRULGHèV DELOLW\ WR VLJQLĆFDQWO\ GH- Prof. Denis Duboc, Cardiologist, Chronic Heart Failure (inactive development) FUHDVHOHYHOVRILQćDPPDWLRQDQGĆEURVLVLQ Hôpital Cochin, Paris Drug development phase: a large panel of skeletal muscles and in the Administered to more heart in a dystrophic mice model. than 150 healthy adults and Chronic Heart 2015 Failure patients (7 phase I trials) Orphan Drug designation granted by the Our hope is that Rimeporide becomes Opportunity: Therapeutic European Medicines Agency (EMA) for a big step forward for the treatment of potential to prolong 5LPHSRULGHLQ'0'DQGĆOLQJRIWKHFOLQL- DMD, alone or in combination with other ambulation and delay cal trial application for European countries. available treatments. In particular, Rime- cardiomyopathy in all patients with DMD; poride has the potential to address the JRRGVDIHW\SURĆOHLQ 2016 and beyond cardiomyopathy in Duchenne, which is at human. Patients are being enrolled in a phase Ib present a progressive condition with very clinical trial. Leading European neuro-pae- limited therapeutic options. To our knowl- diatricians will enroll up to 20 patients with edge, Rimeporide is one of the few clinical DMD during 2016 at the Armand Trousseau stage therapies intended to reduce in- Hospital/ I-motion (Paris, France), the Great ćDPPDWLRQ DQG ĆEURVLV ERWK LQ VNHOHWDO 2UPRQG6WUHHW+RVSLWDO /RQGRQ8. WKH muscles and in the heart. Santa Creu i Sant Pau (Barcelona, Spain) and the San Raffaele Hospital (Milan, Italy).
Along the development path, EspeRare will strive to ensure that patients that are H[SHFWHG WR EHQHĆW IURP WKH PHGLFDWLRQ will have access to it. According to current development plans, Rimeporide aims to be marketed by 2020-2021.
A SOLID NETWORK OF PATIENT GROUPS AND DISEASE EXPERTS TO ADVISE AND STRENGTHEN RIMEPORIDE DEVELOPMENT STRATEGY : TREAT NMD ADVISORY COMMITTEE
R&D funding: French Telethon Key collaboration established Strategic partnership with clinical (AFM) & Swiss Technology & with neuromuscular patient centres of Excellence: Great Innovation (CTI) supports ongoing associations: AFM (France), PPMD Ormond Street Hospital (London, research in nonclinical studies and (Spain), Action Duchenne (UK), MD UK), I-Motion unit, Armand Merck Serono is supporting the Campaign (UK). Trousseau Hospital in Paris, clinical development. France, the Santa Creu i Sant Pau (Barcelona, Spain) and the San Raffaele Hospital (Milan, Italy).
EspeRare | Annual Report 2015 17 Building our portfolio
Second programme: Cilengitide in Focal Segmental Glomerulosclerosis (FSGS)
ABOUT FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Focal Segmental Glomerulosclerosis The damaged glomeruli allow proteins, (FSGS) is a rare kidney disease with an which would not normally do so, to pass incidence of 7 per million. It affects both into the urine. This so-called proteinuria children and adults with peaks at 6-8 and and symptoms secondary to it, such as 20-30 years of age, respectively. swelling (oedema) of the tissues (often the OHJVDQGIHHW FDQEHWKHĆUVWVLJQVRI)6*6 Focal segmental glomerulosclerosis is DQGGLDJQRVLVLVFRQĆUPHGE\NLGQH\ELRS- a disease that results in impaired renal sy. Management of FSGS can require dial- function due to injury and scarring of the ysis and 50% of all cases progress rapidly JORPHUXOL WKH ĆOWUDWLRQ XQLWV ZLWKLQ WKH to end-stage renal disease (ESRD), necessi- kidney. The ability of the glomeruli to act tating a kidney transplant. DVĆOWHUVGHSHQGVRQWKHPKDYLQJDQLQWDFW SK\VLFDOĆOWUDWLRQEDUULHUZKLFKLVPDGHXS Current treatments are essentially aimed of tightly associated specialised cells called at controlling the symptoms of the disease podocytes. The underlying mechanism of and are often inadequate and toxic. FSGS disease is podocyte injury and the conse- is a lifelong chronic disease and the disease quential loss of the physical integrity of the burden to patients is tremendous. The life ĆOWUDWLRQEDUULHU expectancy of a 10 year-old child on hae- modialysis due to end stage kidney disease is dramatically reduced. For FSGS patients, the need for novel and targeted medicines is a matter of urgency. Q
Normal healthy glomeruli (left) with glomer- XORVFOHURVLV ULJKW DFRQGLWLRQZLWKĆEURVLV (scar) of the glomeruli (blue stain). The thin loops of blood vessels are replaced by the blue scar tissue.
(Source: Shutterstock)
18 EspeRare | Annual Report 2015 Cilengitide is a safe, potent and selective žYſ integrin Cilengitide represents an innovative and promising antagonist. It was developed by Merck Serono in a cancer approach that targets podocyte loss in FSGS patients application but was discontinued in Phase III when it failed and that has the potential to translate into a reduction or to meet its primary endpoints. arrest of the decline of renal function.
BACKGROUND CILENGITIDE IDENTITY CARD: 2013 “ What we learn from EspeRare obtained the rights to study cilen- rare disorders often has Name: Cilengitide gitide in FSGS in 2013 Target: žYſ integrin inhibitor profound consequences Originator: Merck Serono Indications: Focal segmental 2014 for our understanding glomerulosclerosis (FSGS, EspeRare started working on the reposi- of more common active development by tioning opportunity for cilengitide in FSGS. conditions.” EspeRare) and oncology A non-clinical study was initiated with Prof. (inactive development) Drug development phase: Moin Saleem’s team, a nephrology and Dr Francis Collins, Administered to over Director of the National FSGS-specialized team from the School of 1600 patients (adults and Clinical Sciences, Bristol University (UK). Institutes of Health children, Phases I to III) for cancer and being evaluated 2015 non-clinically for FSGS Opportunity: *RRGVDIHW\SURĆOHLQ Completion of the in vitro study to assess humans. Cilengitide has the potential of cilengitide in FSGS proven activity on žYſ3 In 2015, Prof. Saleem’s team at Bristol Uni- integrin, a molecule whose versity (UK) completed an in vitro study inappropriate activation is thought to play a major part aimed at testing the ability of Cilengitide in the progression of FSGS to modulate FSGS-induced podocytes’ change of shape and motility. Cilengitide was found to be non-toxic to podocytes and was able to reduce the FSGS-induced žYſ3 integrin activation. This effect has the potential to translate into the clinic as an improvement of renal function for FSGS patients.
2016 onwards EspeRare is looking to explore the poten- tial to use Cilengitide in FSGS and other renal diseases, rare or not, where žYſ integrins have been found to be activated.
A SOLID NETWORK OF DISEASE EXPERTS TO ADVISE AND STRENGTHEN CILENGITIDE’S DEVELOPMENT STRATEGY
R&D funding: co-funding with Strategic partnership with clinical with Prof. Saleem (University of Merck Serono (Switzerland), centres of excellence: Bristol, FSGS patient registry, UK), pending applications for public and Key Opinions Leaders Profs. European Nephrotic Syndrome patient associations funding. Gipson and Kretzler (University Consortium, CoNeCon. of Michigan and NEPTUNE study, USA), on-going collaboration
EspeRare | Annual Report 2015 19 Organisation
The Board and the Executive Committee The strategic and day-to-day activities are constitute EspeRare’s statutory structure. PDQDJHG E\ WKH +HDG RIĆFH DSSRLQWHG by the Board. Ad-hoc committees such The Board is the supreme body that DV VFLHQWLĆF DGYLVRU\ ERDUGV DUH DOVR UDWLĆHVDOOGHFLVLRQV,QOLQHZLWK(VSH5DUH constituted to support the strategic QRQSURĆW VWDWXV ERDUG PHPEHUV DFW RQ D development. In the start-up phase, the voluntary basis and are key opinion leaders Executive Director and the R&D Director in the healthcare and rare disease space. manage a number of part-time employees, The President is Sharon Terry, a pioneer of consultants and volunteers to deliver on patient empowerment and citizen health, EspeRare’s objectives. Q IXUWKHUPRUHWKH&(2RI*HQHWLF$OOLDQFH “As a nonprofit organisation, our Washington DC, USA. priorities are not determined by the size of a market, they are solely defined by the medical needs and great science. Above all, we strive to apply our patient-centric model and pharma know-how to advance new treatments for underserved patients.”
Caroline Kant-Mareda Founder & Executive Director
20 EspeRare | Annual Report 2015 THE FOUNDATION BOARD
MONIQUE A. CAILLAT EWEN SEDMAN Monique A. Caillat is an Attorney at Law (ZHQ6HGPDQLV&KLHI%XVLQHVV2IĆFHUDQG based in Geneva, Switzerland, specialised in Head of the US Research Institute at Merck the healthcare sector. As Board Member, she Serono in Boston, Massachusetts. He is the General Counsel of the foundation. brings wide-ranging leadership expertise With over 20 years of experience in the regu- across the whole pharmaceutical R&D lated industries in Europe and the US, she has value chain. represented the private sector’s interest in its Ewen has led key projects and functions relations with the Authorities, International from early Discovery research to late-stage
2UJDQLVDWLRQV $FDGHPLD DQG 1*2V :KLOH clinical development in a variety of differ- Monique A. Caillat specialised in the counsel to pharmaceutical ent therapeutic areas. Previously he was FRPSDQLHVVWDUWXSVDQGQRQSURĆWRUJDQLVD- responsible for the successful build up of tions in the healthcare sector, Monique is also the Neurodegenerative Disease Research engaged in supporting patient and healthcare unit at Merck Serono. provider interactions through medical media- Ewen holds a combined honours degree in tions and her membership on the Geneva Physiology and Pharmacology. health ethics committee. SHARON F. TERRY BÉATRICE GRECO 6KDURQ LV 3UHVLGHQW DQG &(2 RI *HQHWLF Béatrice Greco is a Founder of EspeRare. Alliance, a network of more than 10,000 She is a Board member and plays an active organisations, including 1,200 disease Béatrice Greco role in the Executive Committee. advocacy organisations. Genetic Alliance Béatrice has a strong background in neuro- enables individuals, families and communi- sciences. In the Serono pharmacology depart- ties to become full participants in the medi- ment, she led a number of drug discovery cal research process. In this context, she projects while heading the translational test- has also developed “Registry for All“ and ing of investigational drugs. Since 2009, biobanking capabilities. within the Platform of Global Health she has 6KH LV WKH IRXQGLQJ &(2 RI 3;( ,QWHUQD- led novel and integrated translational tional, a research advocacy organisation for research programs in neglected diseases. the rare genetic condition pseudoxan- Beatrice’s passion for innovation and her thoma elasticum. She is also the author of particular interest in applying science to numerous peer-reviewed articles and Peter Potter-Lesage address vulnerable patients naturally drove among others, she is a member of the exec- her to co-develop this foundation. utive committee of the International Rare Disease Research Consortium and the US PETER POTTER-LESAGE personalized medicine initiative, a member Peter is the treasurer of the Foundation, a of the board of Telethon-Italy and an member of the Board of Trustees of the Ashoka Fellow. Malaria Consortium (UK) and Senior Advi- sor for fundraising, donor relations and strategy at Medicines for Malaria Venture (MMV) in Geneva, where he previously held the position of founding Chief Finan- Ewen Sedman FLDO2IĆFHUIRU\HDUV Peter is providing to Esperare his expertise LQ ĆQDQFLDO UHSUHVHQWDWLRQ DQG VWUDWHJLF EXVLQHVVSODQQLQJĆQDQFLDODQGIXQGUDLVLQJ DQDO\VLV DQG VXSSRUW ULVN LGHQWLĆFDWLRQ and management.
Sharon F. Terry - President
EspeRare | Annual Report 2015 21 HEAD OFFICE
CAROLINE KANT-MAREDA FLORENCE PORTE-THOMÉ Founder & Executive Director Founder & R&D Director Caroline leads the operations as well as Florence is in charge of developing the develops and implements the foundation’s foundation’s R&D portfolio, driving the pro- strategic plans in concert with the Board grammes from preclinical validation to proof and the R&D Director. She is also a founder of concept in human. As a founder, she also and represents the executive committee sits on the EspeRare’s board. on EspeRare’s board. Florence brings 15 years’ experience in drug She brings broad know-how and interna- development. She joined the pharmaceutical
Caroline Kant-Mareda tional expertise in translational research, LQGXVWU\LQ LQWKHĆHOGRIFOLQLFDOSKDU- public-private partnerships, and product macology, leading translational research and development within the pharmaceutical and managing early clinical studies. Within Merck, information technology industries. Before she became a program leader and success- founding EspeRare, Caroline built and fully led several R&D programs in various managed a R&D department at Merck Ser- therapeutic areas. Recently returning to aca- ono. Prior to that, in the United States, she demia, she led paediatric studies in a Cancer helped launch 3C Interactive, a software Sil- Research Centre in Lyon. Florence holds icon Valley company. Caroline holds degrees degrees in clinical pharmacology and immu- in molecular neurobiology and product nology. GHYHORSPHQW &DUROLQH LQ DQ $6+2.$ IHO- Growing up with a cousin affected with Florence Porte-Thomé low and was appointed CFE Swiss women Duchenne muscular dystrophy and seeing entrepreneur of the year in 2015. him gradually decline, Florence has an uncon- By establishing the EspeRare foundation, ditional motivation to drive this foundation Caroline realises her dream of dedicating forward. herself to address rare diseases in honour of her daughter, and for all children suffer- ing with orphan diseases.
“Fostering access to health for patients that are the most in need is what this foundation is about, and is what I am about.”
Beatrice Greco Founder and member of the Board
22 EspeRare | Annual Report 2015 TEAM
SARAH DELACOSTE GWENAËLLE LAPORTE ACHIM SCHAEFFLER Sarah is an accounting and controlling spe- Gwenaëlle has several years of experience Achim has more than 20 years’ experience cialist. With several years working for Dell in commercial support and marketing in LQ WKH ĆHOG RI &KHPLVWU\ 0DQXIDFWXULQJ Computer, Hewlett-Packard and Swisscom, various industries and as a project manage- and Controls with the Pharmaceutical In- she has been leading accounting and soft- PHQWRIĆFHU6KHLVćXHQWLQ(QJOLVK)UHQFK dustry. His expertise includes the manu- ware setup projects for real estate entities, and German. With her board experience, facturing of small molecules, biologics and LQGXVWU\1*2VDQGWHOHFRPV6KHèVDFWXDOO\ VKHEULQJVDGLYHUVLĆHGVXSSRUWWR(VSH5- Life Cycle Management in large pharma- engaged into humanitarian causes, for an ide- are’s executive team. ceutical companies and biotechs. He brings al of a “better world”. Having a strong IT liter- this solid expertise of drug manufacturing acy, she has been developing web mastering CÉDRIC MERLOT processes to support EspeRare’s drug de- skills, and photography as a semi-pro leisure &«GULF LV WKH &(2 RI 'UXJGHVLJQWHFK velopment programmes. in the last past years. At EspeRare she links which he founded in 2007. After a few ledger accounting to reporting and auditing. \HDUV DW 6DQRĆ$YHQWLV LQ WKH PROHFXODU ANDREW SLADE modelling group, he joined Serono and had Andrew holds a Ph.D. in molecular biology ILARIA DI RESTA LQFUHDVLQJUHVSRQVLELOLWLHVLQWKH6FLHQWLĆF and postgraduate diploma in clinical re- Ilaria has over 13 years of experience in clin- Computing department, with a focus on search. He has a 15 year experience in pre- ical development. She has been responsible data management for small molecules and clinical and early clinical development,and for the design and implementation of clinical biologics and computer-assisted drug de- a strong regulatory and drug manufactur- trials in several therapeutic areas, with a sign for small molecules.He applies bioin- LQJEDFNJURXQG+HEHQHĆWVIURPDQLQWHU- particular focus on rare paediatric diseases. formatics and data management expertise national exposure in large multinational As an expert in clinical site coordination, Key to support the development of the founda- organisations, with an extensive network 2SLQLRQ /HDGHU PDQDJHPHQW DQG FOLQLFDO tion Translational Platform. of preclinical and clinical contacts across study quality management, Ilaria is provid- several therapeutic areas. ing her clinical operation and project man- SANDRA MILLET At EspeRare, Andrew is currently respon- agement expertise to the foundation. 6DQGUD ZRUNHG IRU \HDUV LQ WKH ĆHOG RI sible of the management of preclinical and communication and organisational de- translational activities of the foundation’s HANANE GHEIT velopment, within the Research & Devel- programmes. Hanane is specialised in orphan and pae- opment function at Merck Serono. As a diatric drug development in different project manager in the ETAI communica- DUC TRAN areas such as metabolic diseases and neu- tion group, she launched and developed Duc Tran brings 18 years of experience ro-oncology. She has been running the business events and trade fairs for the in drug discovery and drug development implementation and the coordination of in- manufacturing industry in Europe. Sandra working for large pharmaceutical compa- ternational phase II/III clinical trials in clin- holds a Master in business and commerce, nies and start-ups in cardiovascular, anti-in- ical referral centres for rare diseases. She and recently obtained a Master in Human fective, CNS and reproductive medicine has participated in EU Health programs in Resources and Change Management. She disease areas delivering a large number of paediatrics including a work package ded- brings to the Foundation her solid market- projects into clinical development, up to icated to the early evaluation of new an- ing and communication expertise. PhIIa Proof of Concept. Duc holds degrees ti-cancer compounds in children. Hanane in organic and bioorganic chemistry and is provides her clinical operational expertise SYLVIE RYCKEBUSCH a registered Project Manager. He provides to EspeRare. Sylvie has 12 years of business develop- EspeRare with his expertise in non-clinical, ment experience within Serono Inter- early clinical and manufacturing in support AGNÈS JAULENT national and Merck Serono where she of the foundation’s R&D activities. Agnès studied for her PhD in chemistry occupied various senior roles within Busi- at Imperial College London and then ness Development and Alliance Manage- completed her post doctoral studies at the ment. Prior to establishing her consulting LMB (Laboratory for Molecular Biology) in practice, Sylvie worked within the Index Cambridge, UK. She then joined a biotech Ventures Life Sciences team. She also FRPSDQ\,VRJHQLFDD&52WKDWVSHFLDOLVHV spent 4 years as a strategy consultant with in offering discovery services to the Mckinsey and Company. She provides busi- SKDUPDLQGXVWU\LQWKHĆHOGVRISHSWLGH ness development and licensing support to protein and antibody research. Agnès is EspeRare. DQH[SHUWLQDOOĆHOGVSHUWDLQLQJWRSHSWLGH chemistry and bring this experience to EspeRare as a project manager.
EspeRare | Annual Report 2015 23 SCIENTIFIC ADVISORS
PROF. GHASSAN BKAILY DR. PIERRE CARLIER provides drug development training through his Ghassan Bkaily, Ph.D., is a Professor at the Fac- Pierre Carlier, MD, PhD, CEA, has been heading proprietary web-based drug development acad- ulty of Medicine of Sherbrooke University. His the NMR laboratory of the Myology Institute in emy programme. Julian serves as the Medical re- research focuses on the role biochemical pro- Paris for more than 10 years. This leading specialist sponsible for the Duchenne programme and sub- cesses of the cardiovascular system. He has held in magnetic resonance imaging and spectroscopy sequent programmes in neuromuscular diseases. several important positions, including Chairman of muscle is focusing with his team on developing of the Department of Anatomy and Cell Biology truly quantitative imaging measurements, essen- PROF. ANTOINE HADENGUE and Director of the CIHR Group in Cardiovascu- tial to ensure the clinical relevance of high-tech- Antoine Hadengue is a Professor of Gastroen- ODU,QWHUDFWLRQV+HSXEOLVKHGQXPHURXVVFLHQWLĆF QRORJ\LPDJLQJSURFHGXUHV'HYHORSLQJDQGUHĆQ- terology and Hepatology, at the University Hos- papers and book chapters. His work received ing these quantitative techniques may enable the pitals of Geneva, Switzerland. Graduated from several awards and honours, such as the most detection of very early and pre-clinical signs of a Paris Descartes Faculty of Medicine and special- outstanding pharmacology research paper of the positive response to treatment, thus making MRI ised in gastroenterology and liver cellular biol- Pharmacological Society of Canada (2004). Ghas- and MRS potentially attractive outcome measures RJ\KHĆUVWIRFXVHGRQKHSDWLFSDWKRSK\VLRORJ\ san provides expertise in the mechanism of action in trials. Pierre is engaged in numerous research research. Since 1994, he managed clinical ac- of Rimeporide in the context of cardiomyopathy. projects to further develop MRI&S as a non-inva- tivities, research works and medical practice. In sive diagnostic tool and outcome measure. He pro- 2001, he was nominated Head of the Division of PROF. STÉPHANE BLOT vides EspeRare with his expertise in the imaging of Gastroenterology and Hepatology, Department Stéphane Blot is heading the neurobiology labo- muscles using NMR and MRI imaging techniques. of Internal Medicine, at the University Hospitals ratory of the Veterinary School of Alfort (ENVA), of Geneva, Switzerland. Antoine provides his France. This unit is supported by the French As- PROF. JOEL DUDLEY clinical expertise in support of EspeRare drug sociation against Myopathies. As a teacher-re- Joel Dudley, PhD, is Assistant Professor of development efforts in metabolic diseases. searcher, Prof. Blot gives theoretical and clinical Genomic Sciences and Director of Biomedical In- lessons to veterinary students, trainings in neu- formatics at Icahn School of Medicine at Mount PROF. CONRAD HAUSER rology and neurosurgery and supervises PhD Sinai, New York. His published research covers Conrad Hauser is a physician specialised in students. In parallel he participates among oth- topics in bioinformatics, systems medicine, per- Dermatology, Venereology, Allergy and Clinical ers to the instruction of students preparing the sonal and clinical genomics, drug and biomarker Immunology. From 1993 to 2008, he was chief myopathology diploma of the French Institute discovery. His computational drug repurposing of the Department of Dermatology of Western of Myologie. Stéphane provides EspeRare with work gained recognition by the NIH NHGRI for Switzerland (Bern) and chief of the Allergy Unit, his expertise in conducting animal models of this contribution to Genome Advancement. He division of Immunology and Allergology, within Duchenne muscular dystrophy and in particular is also co-author of the book Exploring Personal the Geneva state hospital and medical school. In the golden retriever muscular dystrophy model. *HQRPLFVIURP2[IRUG8QLYHUVLW\3UHVVWKHĆUVW 2008, he joined the Merck Serono pharma com- major text on personal genome analysis and inter- pany as a Senior Medical Director, and held the DR. SERGE BRAUN pretation. His current research aims to integrate position of head of early development & head of Since 10 years, Serge Braun, Ph.D, is the Scien- DQG DSSO\ LQIRUPDWLRQ IURP PROHFXODU SURĆOLQJ biomarker strategy, global clinical development WLĆF 'LUHFWRU RI RQH RI WKH ELJJHVW SDWLHQW DV- clinical practice, and wearable sensors to realise the Unit Rheumatology. He provides his expert bi- sociation in the world: the French Association vision for a real-time learning healthcare system. In omedical understanding in immunology to the against Myopathies (AFM-Telethon). In this 2014, he was named one of the 100 Most Creative foundation. role, he drives the development of an effective People in Business by Fast Company magazine. His research environment for new treatments in is providing his leading computational drug repur- PROF. JIRI MAREDA rare diseases. He has an extensive background posing expertise to support EspeRare drug rescue After obtaining a PhD in physical organic chem- in neuromuscular biomedical research in France efforts and platform development. istry at the University of Geneva, Jiri Mareda and in the United States. worked as the research associate at the Uni- In 2001, he became Head of Research at Trans- DR JULIAN GRAY versity of Pittsburgh, where he fully specialised gene, worldwide leader in gene therapy, and Julian Gray has 25 years of experience in clinical in computational and theoretical chemistry. worked on cancer immunotherapy and infec- development in the CNS area within the phar- He was then teaching for more than 28 years tious diseases projects. In recognition of his im- maceutical industry, including drug development organic chemistry to chemistry, pharmacy, and pact in rare disease drug development, he was in Duchenne muscular dystrophy and other rare biology students at the University of Geneva. named “Inspirational Stakeholder of the Year” at central nervous system indications. Dr Gray was He was also giving advanced physical-organic WKHWK$QQXDOê:RUOG2USKDQ'UXJ&RQJUHVVë the Medical Director at Santhera where he ran courses for master and doctoral students at the In addition to this role, Dr Braun has an exten- part of the clinical development for Idebenone. Chemistry department. sive background in neuromuscular biomedical +H FRPELQHV TXDOLĆFDWLRQV DQG H[SHULHQFH LQ Jiri now provides an insight at the molecular and research and he is advising EspeRare on the stra- neurology and pharmaceutical development with chemical levels to help tackle challenges that Es- tegic development of Rimeporide in Duchenne. relevant experience in rare diseases. Julian also peRare undertakes.
24 EspeRare | Annual Report 2015 PROF. RAMAIAH MUTHYALA DR. LAURENT SERVAIS DR. ELIA STUPKA With around 30 years of experience in the Laurent Servais is a paediatrician and the director Dr. Elia Stupka is a bioinformatics leading expert pharmaceutical industry, he was involved in of the clinical research department at the Insti- who started his genomics career as part of the commercial successes such as an antiepileptic tute of Myology in Paris. He is graduated from core Human Genome Analysis Team and Ensembl under development approved as orphan drug, Louvain Medical School in Brussels where he group in the UK, where he participated in the the repositioning of a compound developed for obtained his PhD in Neuroscience in 2005. With KXPDQ JHQRPH SURMHFW +H ZDV DOVR 6FLHQWLĆF cancer to treat the rare disease African sleeping 15 years of experience in rare diseases clinical Director at the University College London, sickness or a treatment for a rare thyroid cancer. research, he currently leads the department where he began applying Next Generation Prof. Ramaiah has been working for 10 years of Clinical Research within the French national Sequencing approaches to both rare and com- as Associate Professor in the Department of centre of expertise in clinical myology in Paris. plex disease projects and exploring epigenomics Experimental Clinical Pharmacology and as Ad- In addition to caring for patients with neuro- approaches to identify novel biomarkers. He junct Associate Professor for the Department of muscular diseases within his medical practice, OHG WKH GHYHORSPHQW RI WKH ĆUVW 7UDQVODWLRQDO Medicine of Minnesota University. His research Laurent focuses on the development of clinical Genomics and Bioinformatics Center in Italy activities extend to rare diseases such as orphan outcome measures and clinical trials in muscular at San Raffaele Hospital Research in Milan. cancers and neurological diseases, with a focus dystrophies. Laurent and his team bring medical He currently is the Director of Genomics and RQWKHLGHQWLĆFDWLRQDQGUHSRVLWLRQLQJRIGUXJV expertise to the clinical strategy of EspeRare’s Computational Biology at Boehringer Ingelheim. for orphan diseases. He is a strategic advisor for programme in Duchenne muscular dystrophy. Elia is providing his computational biomedical the foundation’s drug repositioning approach. expertise to develop EspeRare proprietary data PROF. NICOLAS J.C. SIMON analytics platform. DR KANNEBOYINA NAGARAJU Nicolas J.C. Simon, MD, PhD, is a Professor and Kanneboyina Nagaraju, PhD, DVM, is an immu- Chairman of the Department of Pharmacology “Duchenne is a heartbreaking nologist with an expertise in molecular mecha- at Aix-Marseille University, School of Medicine disease. Children like Laurent, nisms of target tissue injury in muscle diseases. Director of the Clinical Pharmaco-Toxicology my cousin, affected with He is a principal investigator at Children’s Unit and Addiction medicine specialist at Sainte this disease are bright and Research Institute Center for Genetic Medicine Marguerite Hospital, Marseille. Nicolas is spe- engaged but as they grow up, WKH\LQH[RUDEO\JHWZHDNHU Research at Children’s National Medical Center cialised in pharmacokinetics and in addictology, DQGH[SHULHQFHWKHORVVRI and a tenured Professor of Integrative Systems he chaired the French Pharmacology and Thera- the few abilities they had %LRORJ\DQG3DHGLDWULFV2QHRIWKHPDLQIRFXVHV peutic Society (SFPT) and is a member of several acquired. I have in my genes the RI 'Ub 1DJDUDMXèV ODERUDWRU\ LV WR GHYHORS DQG medical organisations. Nicolas produced more eagerness to find treatments for validate animal models for neuromuscular dis- than 80 publications in various journals including Duchenne.” eases. With his team, he runs routinely pre- the Clinical Pharmacokinetics. Nicolas brings Florence Porte-Thomé clinical drug testing on neuromuscular disease EspeRare his expertise in pharmacokinetics and Founder and R&D Director models especially in the mdx mouse model of in the modelling of translational data to better Duchenne muscular dystrophy. He is a preclinical optimise its drug development strategy. advisor to EspeRare Duchenne programme. WOLFGANG SCHOLZ PROF. MOIN A. SALEEM Wolfgang Scholz, MD, completed his medical Moin A Saleem, FRCP, Ph.D. is Professor of Paedi- education at the Universities of Mainz and atric Renal Medicine at the Academic Renal Unit, Frankfurt. He specialised in ion transport in Southmead Hospital, Bristol and Children’s Renal the kidney under acidic conditions at the Uni- Unit, Bristol Children’s Hospital. He has more than versity of Mainz. After 16 years of experience 20 years’ experience in fundamental research, in cardiovascular research at former Hoechst especially focusing on understanding the funda- AG, heading a Research Team, he became the PHQWDOPHFKDQLVPVRINLGQH\ĆOWUDWLRQLQRUGHUWR head of cardiovascular research at Merck KGaA understand the basis of glomerular diseases. Darmstadt. He is now heading the drug repo- As part of his research into the basic biology of the sitioning activities at Merck Serono. Wolfgang podocyte, the glomerular cell primarily responsible provides his know-how into NHE biology and IRUWKHFRPSOH[IXQFWLRQRIĆOWUDWLRQKHGHYHORSHG contributes with his cardiovascular biomedical a technique for growing human podocytes in the expertise to EspeRare’s project in Duchenne laboratory. This has been a major methodological muscular dystrophy. advance which allows molecules such as cilengitide to be tested as potential treatments for Focal Seg- mental Glomerulosclerosis.
EspeRare | Annual Report 2015 25 Financial view
EspeRare receives funding from project for pharmaceutical companies, academic of Section 501(c)(3) of the United States partners, patient associations and centres and regulatory agencies to drive Internal Revenue Code. international governmental and public effective development and foster affordable ERGLHV 7KHVH IXQGV DUH XVHG WR ĆQDQFH access to new treatments for rare disease Accounting is entrusted to ‘Eclosion’, the EspeRare portfolio to accelerate SDWLHQWV(VWDEOLVKHGDVDQRWIRUSURĆW6ZLVV the Geneva Life Science incubator facility the cost-effective development of IRXQGDWLRQXQGHUVWDWXWHVGDWHGb0DUFK within which EspeRare is located while unexplored therapeutic opportunities 2013, EspeRare is managed by a foundation KPMG international act as external auditors. for rare neurological and immunological ERDUG D &(2 DQG D VHQLRU PDQDJHU ZLWK diseases. In partnership with patient bHPSOR\HHVDQGbFRQVXOWDQWV(VSH5DUH A global banking relationship was created organisations, EspeRare addresses the key as an organisation is exempt from cantonal with a major Swiss bank for current accounts translational gaps and clinical development and federal taxes and is the equivalent of and cash-management facilities in multiple challenges, acting as a trusted partner an exempt organisation within the meaning currencies. Q
THE FINANCIAL YEAR TO 31 DECEMBER 2015
The year was characterised by a number of exchange loss of CHF 186,159. The de- buted by the three founders, was fully sub- factors. The capital and reserve was commit- crease of GBP-CHF and USD-CHF rates scribed on 31 December 2013. ted, further considerable donations were have occasioned only minor losses. The UHFHLYHGRUFRQĆUPHGIRUWKHIXWXUHVWDII total foreign currency loss thus amounts Donations were recruited, planning was activated and, WR &+) IRU b Total donations recognised in 2015 most important of all, Research & Develop- &+)b amounted to CHF 1,114,698. R&D income ment Project funding repre sented 76% of came to CHF 804,698 including an amount WRWDO H[SHQVHV DQG DPRXQWHG WR Additionally the foundation incurred an of CHF 25,409 deferred from 2014. A to- &+)b (note 8 a-e), quite stable as excess of expenditure over income in 2015 of tal of CHF 1,285,560 was received from compared to CHF 1,176,054 in 2014. CHF 461,758 that is mainly due to 0HUFN6HURQRLQZLWK&+)b expenses incurred for higher-cost activities recognised this year and a further Significantly, in January 2015, the Swiss leading to the entry of the Rimeporide &+)b EHLQJ GHIHUUHG WR National Bank discontinued the minimum programme into clinical development for WR ĆQDQFH FOLQLFDO WULDO DFWLYLWLHV RI 5LPH- ćRRUH[FKDQJHUDWHEHWZHHQ6ZLVV)UDQFV Duchenne muscular dystrophy. poride in Duchenne muscular dystrophy. and Euros. As such, during 2015, the EUR- CHF rate dropped from 1.202350 to Founding Capital Also recognised in 2015 was a contribu- 1.087400, representing a partially realised The Capital Fund of CHF 50,000 contri- tion from AFM Telethon for CHF 150,592.
26 EspeRare | Annual Report 2015 In addition, Awards & Foundation Support Staff General Administration income of CHF 310,000 was recognised At year-end the senior management team D ([SHQVHV KHUH UHćHFW JHQHUDO IRXQGD- from a Geneva foundation and the Foun- FRQVLVWHGRID&KLHI([HFXWLYH2IĆFHU&KLHI tion expenses in overall support of R&D dation Tell & un tel. (Note 7).235,000 was 6FLHQWLĆF2IĆFHUDQGVWDIIPHPEHU)XU- activities (note 8d). Q paid directly by Swiss CTI to our academic thermore, EspeRare has a team of 12 con- partner the University of Geneva and is re- sultants and counts on the support of many corded in the notes as an off-balance-sheet other people including board members, sen- item. (note 7). LRUVFLHQWLĆFDGYLVRUVDQGYROXQWHHUV
SNAPSHOT OF ESPERARE EXPENDITURE 2015
Financial charges & foreign exchange loss 3% Research & Development 76% R&D Rimeporide 89%
Infrastructure 1%
Patients advocacy & fundraising 2%
Foundation set-up 1% R&D Cilengitide Administration staffing 5% 6% R&D new projects & Platform 6%
THE FINANCIAL YEAR AHEAD TO DECEMBER 2016
EspeRare operates in a complex multi-cur- has been implemented and KPMG Interna- grammes is maturing and moving into these rency environment in Geneva, Switzerland. tional appointed as our auditors. later stages of development, the foundation’s The bulk of donations are currently received in 7KHSKLORVRSK\XQGHUOLQLQJ(VSH5DUHĆQDQ- QHHGIRUĆQDQFLDOVXSSRUWLVLQFUHDVLQJ,QWKH Euros, although other currencies such as cial management is that of prudent, conserv- next two years this additional income will be Swiss Francs or US dollars are also involved. ative control, including appropriate return on mobilised in alignment with the foundation 2XWćRZVIRUSURMHFWVDUHPDLQO\LQ&+)(85 interim treasury investments, coupled with fundraising strategy and will enable the and GBP as per the various agreements signed the use of the latest IT solutions for bank expansion of EspeRare’s impact on the ZLWK RXU FROODERUDWLQJ RUJDQLVDWLRQV 2WKHU information, transfers and accounting patients burden suffering for rare diseases. general expenses will normally be in Swiss requirements. Current forecasts, given cer- Francs. The resulting exposure or exchange tain fundraising assumptions, for future Conclusion risk is evaluated at budget time to provide a EspeRare rare disease Research and Devel- 7KH GHWDLOHG ĆQDQFLDO WDEOHV WKDW IROORZ å UHDOLVWLF Ć[HG (85&+) EXGJHW UDWH IRU WKH opment project funding are around CHF Balance Sheet, Statement of Income & year. The accounts are kept in CHF. bPLOOLRQIRU%\WKHHQGRILWLV ([SHQGLWXUH å UHSUHVHQW (VSH5DUH LQ LWV H[SHFWHG WKDW (VSH5DUHèV ĆUVW SURJUDPPH third year of operation where all the various This implies a well-developed treasury will be out-licensed to a commercial partner, EDVLFĆQDQFLDOFRPSRQHQWVRIWKHRUJDQLVD- mana gement and accounting approach, this transaction is expected to bring in capital tion have been established step by step to PDWFKLQJ LQćRZV WR RXWćRZV E\ FXUUHQF\ that will be used to fund the expansion of the FUHDWHDSUXGHQWWUDQVSDUHQWĆQDQFLDOPDQ- and taking timely multi-currency invest- foundation programme portfolio in rare dis- agement framework at the service of its ment and foreign exchange decisions. More- HDVHV LQFOXGLQJ ĆQDQFLQJ WKH êH[SHQVLYHë major goal: the discovery and development RYHU WR EHWWHU UHćHFW LQFUHDVLQJ VFLHQWLĆF clinical development of 2 new programs. As of new medicines for the treatment of rare activity, a new internal accounting structure the EspeRare portfolio of therapeutic pro- diseases. Q
EspeRare | Annual Report 2015 27 ESPERARE BALANCE SHEET TO 31 DECEMBER 2015
NOTES 2015 2014 ASSETS CHF CHF Current Assets Cash & Cash Equivalents 2i 420,00 - BCGE Current Accounts 2i 2 209 701,24 2 072 923,83 Prepaid & Receivables Accounts Receivable - 13 845,55 Withholding Tax & VAT Receivable 8 322,13 695,35 TOTAL CURRENT ASSETS 2 218 443,37 2 087 464,73 Non-current assets Computers & Equipment 2d 7 768,70 7 768,70 (less depreciation) (6 956,32) (4 366,75) TOTAL NON-CURRENT ASSETS 812,38 3 401,95 TOTAL ASSETS 2 219 255,75 2 090 866,68
LIABILITIES Current Liabilities Suppliers 125 097,24 57 560,90 Employees Accounts - 158,05 Social Charges 2 353,20 453,35 Due VAT 11 600,00 - Provisions 2f/9 26 400,00 190 900,00 Accruals 2g 42 315,00 - Deferred Income 656 863,00 25 409,19 TOTAL CURRENT LIABILITIES 864 628,44 274 481,49
CAPITAL & RESERVES Foundation Capital 10 50 000,00 50 000,00 2SHUDWLRQV5HVHUYH 3 1 766 385,19 1 640 274,71 Net excess of (Expenditure)/Income (461 757,88) 126 110,48 TOTAL CAPITAL & RESERVES 1 354 627,31 1 816 385,19 TOTAL LIABILITIES AND CAPITAL 2 219 255,75 2 090 866,68
)RUWKHHDVHRIUHIHUHQFHRIRXUVWDNHKROGHUVHTXLYDOHQW(XURĆJXUHVKDYHEHHQSURYLGHGDWWKHRIĆFLDOHQGRI\HDUUDWHRI for 2014 and 1.087400 for 2015
CASH FLOW AS AT 31 DECEMBER 2015
2015 2014 OPERATING ACTIVITIES CHF CHF Net excess of (Expenditure)/Income (461 757,88) 126 110,48 +Depreciation 2 589,57 2 519,47 +decrease (increase) in Prepaid and Receivables 6 218,77 13 535,72 +increase (decrease) in Short term Liabilities 80 878,14 21 970,41 +increase (decrease) in Provisions (164 500,00) 173 124,65 +increase (decrease) in Accruals 42 315,00 - +increase (decrease) in Deferred income 631 453,81 (124 590,81) &DVKIURPRSHUDWLQJDFWLYLWLHV RSHUDWLQJFDVKćRZ 137 197,41 212 669,92
INVESTING ACTIVITIES 2XWćRZVIRUSXUFKDVHRIWDQJLEOHĆ[HGDVVHWV - (2 226,85) &DVKLQćRZGUDLQIURPLQYHVWLQJDFWLYLWLHV - (2 226,85)
&DVKLQćRZGUDLQIURPĆQDQFLQJDFWLYLWLHV - -
NET CASH 137 197,41 210 443,07
Cash and cash equivalents at begining of period 2 072 923,83 1 862 480,76 Cash and cash equivalents at end of period 2 210 121,24 2 072 923,83
NET CASH 137 197,41 210 443,07
28 EspeRare | Annual Report 2015 ESPERARE STATEMENT OF INCOME & EXPENDITURE FOR THE PERIOD FROM JANUARY 1ST TO DECEMBER 31, 2015
NOTES 2015 2014 INCOME CHF CHF Donations received 2b/7a 804 698,48 1 312 621,59 Financial Income 2k 2 134,06 897,36 2WKHU,QFRPH 329 990,73 167 861,01 TOTAL INCOME 1 136 823,27 1 481 379,96
EXPENDITURE Research & Development Expenditure 2e R &D Projects 8a Rimeporide Research & Development 8b 695 136,14 503 591,83 Support Costs 8g 398 333,74 400 316,29 Legal Fees 8f - 1 653,75 TOTAL R&D PROJECTS, RIMEPORIDE 1 093 469,88 905 561,87
NEW PROJECTS 8c Repositioning Platform 8d - 135 316,34 Support Costs 8g 80 381,15 56 981,59 Cilengitide 8e 32 254,85 25 365,00 Support Costs 8h 15 454,98 52 829,33 TOTAL NEW PROJECTS 128 090,98 270 492,26 TOTAL RESEARCH & DEVELOPMENT EXPENDITURE 1 221 560,86 1 176 054,13
GENERAL FOUNDATION ADMINISTRATION 8d $GPLQLVWUDWLRQVWDIĆQJ YROXQWHHUV 8g 97 622,59 105 483,68 Patient Association Consultancy 335,05 5 057,21 2IĆFH5HQWDO &RVWV 14 052,87 12 849,02 2IĆFH5HQWDO 11 508,00 10 486,00 2IĆFH&RVWV 2 544,87 2 363,02 Accounting & Audit Expenses 26 754,74 29 025,08 Audit Expenses 26 754,74 16 719,08 Accounting Expenses - 12 306,00 2WKHU([SHQVHV 5 071,39 8 539,23 General Insurance 260,40 260,40 IT Expenses 151,60 1 999,75 Communications 4 659,39 6 279,08 General Legal Fees 2 322,04 179,26 Fundraising 31 707,32 705,20 Fundraising direct costs 10 365,53 - Advertising Costs 9 542,84 1 047,00 2WKHU2SHUDWLQJ([SHQVHV 11 798,95 (411,80) Financial Charges 2 733,41 1 639,76 Exchange Differences 2c 188 589,46 12 325,21 Board meeting 5 241,85 892,23 Depreciation 2 589,57 2 519,47 TOTAL GENERAL ADMINISTRATION EXPENDITURE 377 020,29 179 215,35
TOTAL EXPENDITURE 1 598 581,15 1 355 269,48
1(7(;&(662) (;3(1',785( ,1&20( 3 (461 757,88) 126 110,48
EspeRare | Annual Report 2015 29 NOTES TO FINANCIAL STATEMENTS FOR THE YEAR ENDED 31 DECEMBER 2015
1. ORGANISATION 7KH(VSH5DUH)RXQGDWLRQ ê(VSH5DUHë LVD6ZLVV)RXQGDWLRQHVWDEOLVKHGDVDQRWIRUSURĆWOHJDOHQWLW\UHJLVWHUHGLQ*HQHYDXQGHU statutes dated 27th March 2013 and in accordance with article 80 and those that follow of the Swiss Civil Code. It is managed by a foun- dation board, an executive director and 2 senior managers. :LWKLWVKHDGRIĆFHLQ3ODQOHV2XDWHV*HQHYDWKHDLPRI(VSH5DUHLVWREULQJSXEOLFDQGSULYDWHVHFWRUSDUWQHUVWRJHWKHUWRERWK IXQGDQGSURYLGHPDQDJHULDODQGORJLVWLFDOVXSSRUWWRGULYHWKHLGHQWLĆFDWLRQDQGGHYHORSPHQWRIWUHDWPHQWVIRUUDUHGLVHDVHV7KH foundation focuses on accelerating the cost-effective development of unexplored (re)positioning opportunities for rare neurological and immunological diseases. In partnership with patient organisations, EspeRare addresses the key translational gaps and clinical develop- ment challenges, acting as a trusted partner for pharmaceutical companies, academic centres and regulatory agencies to drive effective development and foster affordable access to new treatments for rare disease patients. As with all Swiss foundations recognized for international public good, EspeRare is monitored by the Swiss Federal Supervisory Board for Foundations.
2. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES 7KHVLJQLĆFDQWDFFRXQWLQJSROLFLHVDGRSWHGE\(VSH5DUHLQWKHSUHSDUDWLRQRIWKHĆQDQFLDOVWDWHPHQWVDUHVHWRXWEHORZ a) Accounting principles 7KHDFFRXQWLQJSULQFLSOHVIROORZHGDUHWKRVHRIWKH6ZLVV&RGHRI2EOLJDWLRQVDUWLFOHV WR H b) Recognition of donations &RQWULEXWLRQVIURPGRQRUV ERWKSXEOLFSULYDWHDQGSKLODQWKURSLFVRXUFHV DUHUHFRJQLVHGLQWKHĆQDQFLDOVWDWHPHQWVRQDQDFFUXDOV EDVLVZKHQWKH\KDYHEHHQUHFHLYHGRUFRQĆUPHGLQZULWLQJE\SOHGJHV&RQWULEXWLRQVZKLFKDUHVXEMHFWWRGRQRULPSRVHGVWLSXOD- WLRQVIRUDVSHFLĆFSXUSRVHRUXVHLQIXWXUH\HDUVPD\EHGHIHUUHGRUDWWULEXWHGWRDUHVWULFWHGUHVHUYHDFFRUGLQJWRWKHSDUWLFXODU QDWXUHRIWKHVSHFLĆHGFRQGLWLRQV c) Foreign Currency Transactions Transactions in foreign currencies are translated at the foreign exchange rate ruling at the date of the transaction. Monetary assets and liabilities denominated in foreign currencies at the balance sheet date are translated to CHF at the foreign exchange rate ruling at that date. Foreign exchange differences arising on translation are recognised in the statement of income and expenditure. Non-monetary assets and liabilities that are measured in terms of historical cost in a foreign currency are translated using the exchange rate at the date of the transaction. The following exchange rates were used at year-end: 1 EUR = CHF 1.087400 1 USD = CHF 1.001012 1 GBP = CHF 1.475340 G )L[HGDVVHWV Fixed assets are stated at cost less accumulated depreciation. Depreciation is charged to the statement of income and expenditure on a straight line basis over the estimated useful lives of the assets. The estimated useful lives of assets are as follows: • RIĆFHIXUQLWXUH \HDUV • Ć[WXUHVDQGLQVWDOODWLRQV \HDUV • computers and equipment 3 years e) Research and Development ([SHQGLWXUHDQGJUDQWVDOORFDWHGIRUUHVHDUFKDFWLYLWLHVDUHXQGHUWDNHQZLWKWKHSURVSHFWRIJDLQLQJQHZVFLHQWLĆFRUWHFKQLFDO knowledge and understanding for the development of therapeutic assets in rare diseases. They are recorded on a contract or letter of understanding basis, the expense being accounted for by EspeRare at the moment of allocation and initial payment. In the case of any portion remaining unpaid at the year-end, it is included under current provisions and accruals. Regulatory and other uncertainties inherent in the development of new products in this sector preclude EspeRare from capitalising development costs. f) Provisions A provision is recognised in the balance sheet when EsperRare has a present legal or constructive obligation as a result of a past HYHQWDQGLWLVSUREDEOHWKDWDQRXWćRZRIHFRQRPLFEHQHĆWVZLOOEHUHTXLUHGWRVHWWOHWKHREOLJDWLRQRQDPLGWHUP \HDUV g) Accruals $QDFFUXDOLVUHFRJQLVHGLQWKHEDODQFHVKHHWZKHQ(VSH5DUHKDVDIDLUFHUWLWXGHWKDWDQRXWćRZRIHFRQRPLFEHQHĆWVZLOOEHUHTXLUHG to settle the obligation in the short term (1 year). K (PSOR\HH%HQHĆWV Pension Plan (VSH5DUHèVSHQVLRQSODQLVFODVVLĆHGDVDGHĆQHGFRQWULEXWLRQSODQ&RQWULEXWLRQVWRWKHGHĆQHGFRQWULEXWLRQSHQVLRQSODQDUHUHFR gnised as an expense in the statement of income and expenditure as incurred.
30 EspeRare | Annual Report 2015 i) Cash and Cash Equivalents Cash and cash equivalents comprise cash balances of current accounts and are valued at nominal value. j) Impairment The carrying amounts of the EspeRare’s assets are reviewed at each balance sheet date to determine whether there is an indication of impairment. If any such indication exists, the asset’s recoverable amount is estimated. An impairment loss is recognised whenever the carrying amount of an asset exceeds its recoverable amount. k) Financial Income Interest income is recognized in the income statement as earned. O ,QFRPH7D[ EspeRare has received exoneration from income tax from the Geneva cantonal and Swiss federal authorities from the year 2013 for 10 years.
3. RESERVES Operations reserve 7KH2SHUDWLRQV5HVHUYHUHSUHVHQWVH[FHVVRIGRQDWLRQVRYHUH[SHQGLWXUHIRUWKHSHULRGDQGLVIUHHO\DYDLODEOHWREHXWLOLVHGIRU future operation and project funding costs as the evolving research and development project pipeline dictates.
4. FINANCIAL INSTRUMENTS a) Foreign currency risk EspeRare incurs foreign currency risk on pledged or effective contributions that are denominated in a currency other than Swiss )UDQFVDQGRQFDVKDQGGHSRVLWVWKDWDUHGHQRPLQDWHGLQRWKHUFXUUHQFLHV2Q-DQXDU\WKH6ZLVV1DWLRQDO%DQNGLVFRQ- WLQXHGWKHPLQLPXPćRRUH[FKDQJHUDWHEHWZHHQ6ZLVV)UDQFVDQG(XURV$VVXFKGXULQJWKH(85&+)UDWHGURSSHGIURP 1.202350 to 1.087400, representing a loss of CHF 186’159. The decrease of GBP-CHF and USD-CHF rates have occasioned only PLQRUORVVHV7KHWRWDOIRUHLJQFXUUHQF\ORVVDPRXQWVWR&+)bè IRU è b) Interest rate risk (VSH5DUHGRHVQRWKDYHDQ\VLJQLĆFDQWH[SRVXUHWRLQWHUHVWUDWHULVNV c) Credit risk In accordance with credit policy, exposure to credit risk, principally as regards contributions, is monitored on an ongoing basis. EspeRare’s liquid assets are kept in cash or low-risk short-term deposits. $WWKHEDODQFHVKHHWGDWHWKHUHZHUHQRVLJQLĆFDQWFRQFHQWUDWLRQVRIFUHGLWULVN7KHPD[LPXPH[SRVXUHWRFUHGLWULVNLVUHSUHVHQWHG E\WKHFDUU\LQJDPRXQWRIHDFKĆQDQFLDODVVHWLQWKHEDODQFHVKHHWSULQFLSDOO\DFFRXQWVUHFHLYDEOHVKRUWWHUPGHSRVLWVDQGFDVK d) Fair value 7KHIDLUYDOXHRIĆQDQFLDOLQVWUXPHQWVKHOGDW'HFHPEHUGRHVQRWGLIIHUIURPWKHLUFDUU\LQJDPRXQWVVKRZQLQWKHEDODQFHVKHHW
5. COMMITMENTS $VDW'HFHPEHUWKHUHZHUHQRVLJQLĆFDQWFDSLWDOH[SHQGLWXUHFRPPLWPHQWV
6. SUBSEQUENT EVENTS 1RHYHQWVRFFXUUHGVXEVHTXHQWWR'HFHPEHUDQGSULRUWRWKHDSSURYDORIWKHĆQDQFLDOVWDWHPHQWVWKDWZRXOGUHTXLUHPRGLĆ- FDWLRQRIRUGLVFORVXUHLQWKHĆQDQFLDOVWDWHPHQWV
7. INCOME Donations received a) During 2015 the following donations were granted
Donor Currency Total Grant Received Recognised Deferred Notes 2015 CHF 2015 CHF 2016 CHF R&D Income
ARES Trading SA EUR 1,200,000 1,285,560 628,697 656,863 I&E Statement - Rimeporide 0HUFN6HURQR$IĆOLDWH
ARES Trading SA EUR 20,889 0 25,409 I&E Statement - Cilengitide deferred in 2014 0HUFN6HURQR$IĆOLDWH AFM telethon EUR 143,231 150,592 150,592 Grant Rimeporide fully committed in 2015 TOTAL 1,364,120 1,436,152 804,698 656,863 R&D Income Awards & Foundation Support Fondation Tell & Un tel CHF 10,000 10,000 10,000
Geneva Foundation CHF 300,000 300,000 300,000 For foundation Scale-up
TOTAL 310,000 310,000 310,000 Awards & Support
2XWRIDWRWDORI&+)UHFHLYHGIURP$(5(67UDGLQJ6$WRFRĆQDQFHWKH5LPHSRULGHFOLQLFDOWULDOLQ'XFKHQQH&+) ZDVUHFRJQL]HGLQWRIXQGWKHSURGXFWLRQRI5LPHSRULGH and preparatory activities for the trial, CHF 656,863 are deferred to 2016 to fund Rimeporide clinical trial activities. 5 'LQFRPHRI&+) IRU&LOHQJLWLGHZDVUHFHLYHGIURP$5(67UDGLQJ6$LQDQGUHFRJQL]HGLQRXUDFFRXQWVLQb
EspeRare | Annual Report 2015 31 b) As a comparison during 2014 the following donations were granted: Donor Currency Total Grant Received Recognised Deferred Notes 2014 CHF 2014 CHF 2015 CHF R&D Income ARES Trading SA EUR I&E Statement - Rimeporide 0HUFN6HURQR$IĆOLDWH bb bb bb ARES Trading SA EUR I&E Statement - Cilengitide 0HUFN6HURQR$IĆOLDWH b b b b AFM telethon EUR b b b Grant Rimeporide fully committed in 2014 TOTAL b b bb bb b R&D Income Awards & Foundation Support $6+2.$ EUR b b b Award fully committed in 2014 /RWHULH5RPDQGH CHF b b I&E Statement - Repositioning Platfrom TOTAL b b Awards & Support Awards & Foundation Support Commission of Technology EUR Rimeporide - Research & Development DQG,QIRUPDWLRQ b b 'RQDWLRQIURP/RWHULH5RPDQGHRI&+)ZDVUHFHLYHGLQDQGUHFRJQL]HGLQRXUDFFRXQWVLQb *UDQWGLUHFWO\WUDQVIHUUHGWRDFDGHPLFSDUWQHUDW8QLYHUVLW\RI*HQHYD
8. EXPENSES a) Principal current R&D projects in rare diseases b) Development of Rimeporide in Duchenne muscular dystrophy in partnership with Merck KGaA c) Prospection & generdrug development opportunities for rare diseases d) Repositioning platform development to support the systematic discovery and evaluation of new projects e) Development of Cilengitide in Focal Segmental Glomerulosclerosis in partnership with Merck KGaA f) General Foundation expenses in overall support of R&D activities J 5HODWHVWRVWDIIDQGWUDYHOFRVWVWKDWDUHUHFRUGHGDQGDOORFDWHGWRWKHVSHFLĆFDFWLYLWLHV7KHVWDIIKHDGFRXQWUHSUHVHQWHGVHQLRU PDQDJHUVDQGWZR5 'SURJUDPPDQDJHUV,QDGGLWLRQ(VSH5DUHEHQHĆWVIURPDQXPEHURIFRQVXOWDQWVDQGYROXQWHHUV7RWDOVWDII EHQHĆWVIRUDPRXQWWR&+) è 6DODULHV 6RFLDOFKDUJHVDPRXQWWR&+)è 7UDYHO([SHQVHVDPRXQWWR CHF 27’345.90 and Volunteers reimbursements amount to CHF 1460.06). The allocation of salaries & social charges to the two R&D projects, repositioning platform and to the Foundation General Adminis- tration according to the percentage of the time spent by employee on the three activities. K $OOOHJDOIHHVDGYLFHIRUFRQWUDFWQHJRWLDWLRQDQGĆQDOL]DWLRQUHODWHGWRWKH5LPHSRULGHSURMHFW
9. PROVISIONS During 2015 the following provisions were incurred and other were carried over from past years: Provisions 2015 2014 EUR CHF CHF EUR Rent 2013 7,200 6,621 7,200 6,621 Rent 2014 9,600 8,828 9,600 8,828 Rent 2015 9,600 8,828 TOTAL 26,400 24,278 16,800 15,450
As per ‘Eclosion Incubation Contract’ = 20m3DW&+)åSHUPRQWK&+)åPRQWKO\LQIUDVWUXFWXUHFKDUJH
10. FOUNDATION CAPITAL The Capital Fund is fully subscribed at CHF 50,000 as stipulated under the original legal statutes of EspeRare dated 27 March 2013. This founding capital was donated by the three initial individual founders.
11. GOVERNANCE The Foundation Board is the Foundation’s supreme body. It takes all decisions necessary or effective for the achievement of the Founda- tion’s aims. It has general responsibility for the affairs of the Foundation and supervises all activities carried out under its authority by the Foundation’s other bodies to which power and authority have been delegated. 0HPEHUVRIWKH%RDUGDFWRQDYROXQWDU\EDVLVDQGPD\QRWFODLPDQ\ĆQDQFLDOFRPSHQVDWLRQRWKHUWKDQH[SHQVHVLQFXUUHGVXFKDV travel and accommodation. For activities over and above the normal requirements of the position, each Member may receive appropriate reimbursement and compensation. Payment of any such reimbursement or compensation is only permissible where it corresponds to a VHUYLFHFDUULHGRXWIRUWKHEHQHĆWRIWKH)RXQGDWLRQ Employees paid by the Foundation such as the Executive Director and the R&D Director serve on the Board only in an advisory capacity and have no voting rights.
12. RISKS AND UNCERTAINTIES (VSH5DUHHQFRXQWHUVFHUWDLQULVNVDQGXQFHUWDLQWLHVLQFRQGXFWLQJLWVDIIDLUV7KHVHULVNVDQGXQFHUWDLQWLHVKDYHĆQDQFLDOVWDWHPHQW LPSOLFDWLRQV,QDOOLQVWDQFHVWKHVHKDYHEHHQFRQVLGHUHGLQWKHĆQDQFLDOVWDWHPHQWVGHVSLWHWKHIDFWWKDWWKHRXWFRPHVRIWKHVHXQFHU- tainties can not be predicted with absolute certainty. Management has concluded that provisions for these risks are appropriate, and any DGYHUVHUHVROXWLRQRIWKHVHXQFHUWDLQWLHVZLOOQRWKDYHDPDWHULDOLPSDFWRQWKHĆQDQFLDOSRVLWLRQRUUHVXOWVRIWKHIRXQGDWLRQ
32 EspeRare | Annual Report 2015 EspeRare | Annual Report 2015 33 How can I support EspeRare?
EspeRare is a foundation recognised by the The foundation is also a member of As an individual or as a corporate organ- Swiss authorities to be operating for the the Transnational Giving Europe (TGE) isation, there are many ways to support LQWHUQDWLRQDO SXEOLF EHQHĆW $V VXFK LW LV network, which allows European citizen EspeRare. fully tax exempt and eligible for Swiss and to make cross-border donations while still international subventions as well as non- EHQHĆWLQJIURPWKHWD[DGYDQWDJHVRIWKHLU ĆQDQFLDOVXSSRUW country of residence.
I WANT TO SUPPORT I WANT TO DONATE TO A I WANT TO ESTABLISH A THE FOUNDATION SPECIFIC R&D PROGRAMME CORPORATE PARTNERSHIP
6XSSRUWLQJXVĆQDQFLDOO\RUWKURXJK 2XU ĆQDQFLDO VWUXFWXUH LV FRPSRVHG If you would like to commit fundraising volunteering action, you will help of several sub-funds, each of them activities or a corporate donation us to further secure the impact of GHGLFDWHGWRDVSHFLĆF5 'SURJUDPPH WR (VSH5DUH PLVVLRQ ZH FDQ GHĆQH (VSH5DUH DQG WKH LGHQWLĆFDWLRQ RI Your donation will support the disease with you the most appropriate way to new treatments for children with of your choice and accelerate the make this happen. rare diseases. development of a new treatment.
We are happy to give you further information and answer your questions: Individuals: [email protected] Corporate organisations: [email protected]
34 EspeRare | Annual Report 2015 THEY SUPPORT US
EspeRare | Annual Report 2015 35 c/o Eclosion 14 chemin des Aulx &+3ODQOHV2XDWHV*HQHYD Switzerland Phone +41 22 794 4004 Fax +41 22 794 4005 Email [email protected] Website www.esperare.org
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