Prosensa Therapeutics R&D in ultra-rare disease European Business Development Conference Dusseldorf, September 24, 2013 Tina C Flatau VP Alliances and Project Management
Forward-Looking Statements This presentation may contain statements that constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forwardlooking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or Prosensa s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as may, might, will, should, expects, plans, anticipates, believes, estimates, predicts, projects, potential, outlook or continue, and other comparable terminology. Forward-looking statements are based on management s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the timing and conduct of clinical trials of drisapersen and Prosensa s other product candidates, plans to pursue research and development of product candidates for DMD and other indications, the clinical utility of Prosensa s product candidates, the timing or likelihood of regulatory filings and approvals, Prosensa s intellectual property position, expectations regarding payments under Prosensa s collaborations and Prosensa s competitive position. These risks and uncertainties also include those described under the captions Risk Factors and Management s Discussion and Analysis of Financial Condition and Results of Operations in Prosensa s Registration Statement on Form F-1 and future filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and Prosensa does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement. 2
Our Mission To develop innovative, RNA-based therapeutics to fill unmet medical needs for patients with rare genetic diseases
Our story Rare disease company founded in 2002 and grown out of the University of Leiden, the Netherlands Our lead compound is in Phase III for Duchenne Muscular Dystrophy We have a pipeline of genotype-specific treatments for Duchenne and other neuromuscular diseases Our technology is an RNA modulation platform, applicable to rare and common diseases Our biggest collaboration is with GSK for selected parts of our Duchenne pipeline 4
BioPartner Accelerator BioPartner Incubator Key collaboration University Leiden Key collaboration Dutch Authorities GMP inspection 2011 2013 2010 2009 Employees: 80+ PNAtix Prosensa Therapeutics BV Dutch Authorities GMP licence 2007 2008 Start PRO051 Clinical phase III 2006 2005 2001 2002 2003 2004 Employees: 39 Start PRO044 Clinical phase I/II 2002 Employees: 7 Start PRO051 Clinical phase I/II Employees: 3 First human study
Duchenne Muscular Dystrophy Age 0 5 10 15 20 25 30 walking problems wheel chair - skeletal deformity very limited use of arms ventilation at night ventilation 24 h death Clinical symptoms
Duchenne Muscular Dystrophy Cause: no dystrophin protein in muscles
Dystrophin
R&D Pipeline Indication Compound Discovery Pre-clinical Phase I/II Phase III Duchenne Myotonic Dystrophy Huntington s Disease PRO051 PRO044 PRO045 PRO053 PRO052 PRO055 PROSPECT PRO135 PRO289 drisapersen License GSK Option GSK Unencumbered Prosensa
the biotech dilemma to partner or not to partner
Biopharma and the importance of collaborations Emerging biotech companies Academic background and links Good IP basis Work virtually used to collaborations Innovative, energetic Need Good friends advisors, investors, backers A flow of $$ to keep working and grow Guidance A realistic growth/ game plan Good connections 11
Why collaborate with Big Pharma? Development is too costly for innovator companies Research Preclinical Clinical 12
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Why collaborate with Big Pharma? Experience Guidance Learning Proven track record Get you there safely A guiding partner focused on getting you to where you want to be
Biotechnology..drug development with more twists and turns Umm I have never done it like THIS before
Pharma partners may be prepared to help us create the development pathway
and prefer a quiet collaborator
Rare disease development is difficult
Rare disease biotech to boldly go where no man has gone before
Expedited development and ultra-rare disease Speed Patient groups urge us to push ahead with progress choose speed over perfection DMD is ultra-rare, disabling and ultimately fatal We aim to generate evidence for expedited development of a whole series of similar treatments Challenges Ultra-rare diseases tend to not be studied well; no treatment so no diagnostic pathway; no imperative from payers to improve on an existing treatment Clinical end points yet to be validated in regulatory submissions; no proven surrogate EMA PIP applies even for rare childhood disease so you have to start out with an end to end plan FDA: Orphan drugs are held to the same statutory requirements for demonstrating effectiveness and safety
Patients
Patient Organizations Are partners on this journey of exploration They put pressure on politicians, regulators and payers They shape the development of regulatory policy They raise $$ to support research and development They help to educate us to understand life with the disease They help develop measures for outcomes and quality of life
the rare disease community
communication newborn screening creating disease awareness informing patients establishing registries
communication or promotion? newborn screening creating disease awareness informing patients establishing registries enlarging the market generating more revenues promotion to consumers lining up patients
patients as partners talking ABOUTpatients
balanced communication with patients information
Hello, We are a family from xxx. We have a son. His name is xxx and he is diagnosed with muscular dystrophy -deletion of exons 49 and 50. We have tested him in genetics labs in xxx, yyy and zzz. He was diagnosed when he was 11 years old. In August xxx will be 17. He is very determined boy, and he believes with stretching and exercising he will walk soon again. I am sending you all the test results we have, and if it is necessary we will make more or different tests. Please help our son. It is a dream of a mother and a father. We are ready to do anything that will help our son feel better.
USA orphan designations and approvals to 2009 A.Pariser, FDA: Orphan drugs must demonstrate substantial evidence of effectiveness/clinical benefit (according to 21CFR 314.50) Substantial evidence of benefit requires adequate and well controlled clinical trials There is no one right way to do things for rare diseases
Hurdles in Rare Disease Development Rare diseases are complex and heterogenous Costly and slow to find subjects for studies Difficult biology and end points Disease natural history not well-studied or understood Standards of care vary widely and affect outcomes In many territories there is no infrastructure to screen, record and locate subjects Lack of well-defined end point makes studies hard to design and regulatory and payer proofs hard to make Regulators are unlikely to have an expert reviewer for the rare disease in question Only the potentially large markets are prioritized by pharmas [E. Kakkis CureTheProcess Campaign]
sustainable pricing
European Orphan Medicinal Products Regulation Introduced in 2000 Aims to encourage development of orphan drugs Orphan drugs have been a very small part of the overall drugs budget. Now there is growing concern with: High prices of orphan drugs Inability to meet the standard measures of cost-effectiveness used by payers In Europe, proposals for better ways to assess in terms of valuefor money to the healthcare system
Paying for the Orphan Drug System: break or bend? Is it time for a new Evaluation system for payers in Europe to take account of new rare disease treatments? Orphanet Journal of Rare Diseases 2012, 7:74.. Wills Hughes-Wilson (wills.hughes-wilson@sobi.com)... Ana Palma (apalma@shire.com). Ad Schuurman (ASchuurman@cvz.nl). Steven Simoens (steven.simoens@pharm.kuleuven.be).
Health Technology Assessments Rare Disease Proposed evaluation criteria: Rarity Investments Efficacy uncertainty Manufacturing complexity Follow-up measures being undertaken Disease severity Lack of alternative therapies Impact of treatment/ disease modification Unique target disease
Achievements small biotech
Speed vs reach + big pharma
Big Pharma vs Small Biotech development capabilities contacts with regulators payer relationships manufacturing know-how commercial infrastructure research capabilities patient proximity fast decision making entrepreneurial spirit sense of urgency Adapted for standardized R&D- Commercialization Specialized, adaptive and interconnected for Rare Disease R&D
Drisapersen Clinical Program Repeat dose escalation (5wks) PRO051-CLIN-02 12 Subjects, 0.5-2-4-6 mg/kg/week DMD114118 Dose-escalation, placebo controlled (3:1) 18 Non-ambulant subjects -> 12mg/kg single dose PK/safety Dose regime comparison, placebo-controlled (2:2:1:1) DEMAND II/DMD114117 53 Subjects; 6mg/kg, 24 wks efficacy/48 wks safety DEMAND III/DMD114044 DEMAND V/DMD114876 Pivotal study, placebo-controlled (2:1) 186 Subjects; 6mg/kg/week, 48 weeks Extension study ongoing (more than 3 years) 12 Subjects; 6mg/kg/week Dose comparison, placebo-controlled (2:2:1:1) 51 Subjects; 3 or 6mg/kg/week, 48 weeks DEMAND IV/DMD114349 Extension study for DEMAND II and III the largest R&D effort ever in DMD Completed Enrolled DEMAND VI Natural History study 250 subjects (aged 3 18 years), 3 year follow-up More than 300 patients in fully enrolled or completed studies
Drisapersen Clinical Program the the the the the the the the most most most most most most most most global global global global global global global global effort effort effort effort effort effort effort effort ever ever ever ever ever ever ever ever in in in in in in in in DMD DMD DMD DMD DMD DMD DMD DMD More than 50 trial sites in 25 countries on 5 continents More than 50 trial sites in 25 countries on 5 continents
Thank you