 BioMarin Pharmaceutical Inc. to Acquire Prosensa Holding N.V. “BioMarin is dedicated to the rare disease community, and the acquisition of Prosensa fits strategically with our mission of delivering therapies that address serious unmet medical needs. We are committed to working closely with regulatory authorities worldwide in bringing a potentially breakthrough therapy to patients with this devastating condition. We will leverage our experience at developing rare disease therapies to bring drisapersen to market as quickly as possible. Further, if we are successful in advancing drisapersen to early regulatory approvals, we believe this transaction could be accretive to operating and GAAP profitability in 2017.” - Jean-Jacques Bienaimé Chief Executive Officer BioMarin Pharmaceutical Inc. November 24, 2014 Exhibit 99.1 |
 2 Safe Harbor Statement This non-confidential presentation contains ‘forward-looking statements’ about the business prospects of BioMarin Pharmaceutical Inc., including potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin’s product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors detailed in BioMarin’s filings with the Securities and Exchange Commission such as 10-Q, 10-K and 8-K reports. |
 3 Additional Information The Offer described in this communication and related exhibits has not yet commenced, and this communication and related exhibits is neither an offer to purchase nor a solicitation of an offer to sell any ordinary shares of Prosensa or any other securities. On the commencement date of the Offer, a tender offer statement on Schedule TO, including an offer to purchase, a letter of transmittal and related documents, will be filed with the United States Securities and Exchange Commission (the “SEC”). Thereafter, Prosensa will file a solicitation/recommendation statement on 14D-9 with the SEC. The offer to purchase ordinary shares of Prosensa will only be made pursuant to the offer to purchase, the letter of transmittal and related documents filed as a part of the Schedule TO. INVESTORS AND SECURITY HOLDERS OF PROSENSA ARE URGED TO READ BOTH THE SCHEDULE TO (AND THE INCLUDED OFFER TO PURCHASE) AND THE SOLICITATION/ RECOMMENDATION STATEMENT, AS THEY MAY BE AMENDED FROM TIME TO TIME, AND OTHER RELEVANT DOCUMENTS FILED WITH THE SEC WHEN THEY BECOME AVAILABLE BEFORE THEY MAKE ANY DECISION WITH RESPECT TO THE TENDER OFFER, BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE TERMS OF THE OFFER, THE PROPOSED TRANSACTIONS AND THE PARTIES THERETO. The tender offer statement will be filed with the SEC by the Company and Buyer, and the solicitation/recommendation statement will be filed with the SEC by Prosensa. Investors and security holders may obtain a free copy of these statements (when available) and other documents filed with the SEC at the website maintained by the SEC at www.sec.gov or by directing such requests to the Information Agent for the tender offer that will be named in the tender offer statement. The Offer described in this current report on Form 8-K and related exhibits has not yet commenced, and this current report on Form 8-K and related exhibits is neither an offer to purchase nor a solicitation of an offer to sell any ordinary shares of Prosensa or any other securities. On the commencement date of the Offer, a tender offer statement on Schedule TO, including an offer to purchase, a letter of transmittal and related documents, will be filed with the United States Securities and Exchange Commission (the “SEC”). Thereafter, Prosensa will file a solicitation/recommendation statement on 14D-9 with the SEC. The offer to purchase ordinary shares of Prosensa will only be made pursuant to the offer to purchase, the letter of transmittal and related documents filed as a part of the Schedule TO. |
 4 Strategic Drivers for Acquisition Product Rationale Financial Rationale Company Rationale • Drisapersen addresses 10,000 seriously ill patients with limited treatment options • Drisapersen has a large body of clinical data that could support early regulatory approval • Drisapersen has initiated NDA filing under Breakthrough designation • Strong patent protected technology platform • Substantial near-term revenue potential • With early approvals in US and EMA, accretive to operating and GAAP earnings in 2017 • Significant value creation even if approval is delayed • Upfront cash consideration represents about 5% of BioMarin’s market cap • Leverages our global regulatory and commercial infrastructure and leadership in orphan disease market • Adds what could be our largest product to a well diversified product portfolio • A potentially trans- formative investment that is risk managed • Follow-on Prosensa products address 35,000 additional DMD patients Initial Focus is Approval of Drisapersen |
 5 Why Prosensa? First to file in the U.S. for the treatment of Duchenne muscular dystrophy Our belief that the totality of drisapersen data combined with the significant unmet medical need of this patient population provide a path to early approvals Largest data set in DMD comprising three placebo-controlled studies and two long-term open label studies, treating over 300 patients New Drug Application (NDA) with Breakthrough Therapy designation currently under rolling review based on existing data; complete NDA submission expected 1Q15; MAA in EMA expected 2015 In-line with FDA guidance, two confirmatory post-approval studies to support accelerated approval planned to begin 1H15 Issued U.S. patents through 2023; EU through 2021; potential for extensions Low dose that supports sub-cutaneous route of administration Anticipated low COGS and available manufacturing capacity to meet market demand |
 6 Evolution of clinical symptoms of DMD 0 5 10 15 20 25 30 Age X-linked, rare genetic disease Rapid progression of muscle degeneration 75,000 patients in addressable populations Severely debilitating and invariably fatal progressive neuromuscular disease Duchenne Muscular Dystrophy (DMD) Walking problems Wheelchair/skeletal deformity Very limited use of arms Ventilation at night Ventilation 24 h Death |
 7 Lead Compound - Drisapersen 20-mer Antisense Oligonucleotide (AON) with specific binding to exon 51 of dystrophin gene pre-mRNA Administered by once weekly subcutaneous injection (6mg/kg) May address up to 13% of the DMD population, or 10,000 patients Granted orphan drug status in US, EU, Japan, Australia Breakthrough Therapy designation granted by the FDA NDA submission initiated under rolling review and Fast Track status |
 8 Available Evidence Supports Potential Early Approvals Two supportive randomized Phase 2 studies Long-term extension studies favorable Generally positive trends across younger subgroups in Phase 3 study Some supportive pharmacologic evidence – MRI, CK and small improvement in dystrophin in the most positive Phase 2 study Low discontinuation rate due to adverse events |
 9 Drisapersen Clinical Data on Over 300 DMD Patients |
 10 10 5 0 15 Semi- tendinosus Bicep femoris Vastus Vastus Vastus lateralis intermedius medialis Rectus femoris Fat replaces muscle as disease progresses Preliminary MRI data suggest reduced fat infiltration DEMAND V: Change in apparent fat fraction from baseline [%] at 48 weeks in 6 muscle groups Placebo (n=5) Drisapersen 6mg/kg/week (n=5) Muscle Pathology: Reduced Fat Infiltration |
 11 DEMAND II (DMD114117) (25 week endpoint) +32m (n=18) DEMAND V (DMD114876) (24 week endpoint) +16m (n=18) -11m (n=16) 6MWD = +31m p=0.003 6MWD = +27m p=0.069 6MWD = +35m p=0.014 DEMAND II + DEMAND V (DMD114117 + DMD114876) (post-hoc analysis 24/25 weeks) -4m (n=18) Drisapersen 6 mg/kg/week Placebo Two placebo-controlled studies show treatment benefit on 6MWD +20m (n=36) -11m (n=34) Placebo Controlled Phase II Studies - 6MWD |
 12 Positive Results in Younger Patients in Phase 3 Study |
 13 Drisapersen Long-term Benefits vs. Natural History Natural History: At one year: ~43m decline At two years: ~125m decline Mean Change Baseline 6MWT Drisapersen P2 extension study after 177wks: All 10 patients:.~25m decline Ambulatory only patients: ~33m improvement Drisapersen P2 extension study Source: Goemans N et al., Neuromuscul Disord (2013) |
 14 Additional Favorable Long Term Data (Phase 2 and 3) |
 15 Drisapersen: Totality of 6MWT Data |
 16 Drisapersen is Well-Tolerated • Two discontinuations due to adverse events (N=285) • one glomerulonephritis • one intracranial venous sinus thrombosis/spinal pain • No deaths occurred in phase II and III placebo-controlled studies • In placebo-controlled study SAEs occurred infrequently and majority unrelated • 8 (8.4%) subjects in the placebo group and • 16 (8.2%) subjects in the drisapersen group • Most common side effects: injection site reactions and renal abnormalities (subclinical proteinuria) • The majority were mild to moderate in intensity • There were no clinically meaningful treatment differences in AEs related to inflammation • Infrequent, moderate to severe thrombocytopenia in open-label extension study |
 17 FDA Has Indicated that Prosensa’s Phase 2 Data May be Sufficient for Accelerated Approval 6 minute walk could be considered a finding on an intermediate clinical endpoint that could have the potential to support accelerated approval Existing clinical data needs to be reasonably likely to predict a long-term beneficial effect in order to obtain accelerated approval Confirmatory study will be required - 269 patients already enrolled in longitudinal natural history study - Expect report on first 80 natural history patients in April 2015 ……..but need to explain Phase 3 |
 18 * Data shown are mean(range) + Data shown are mean(95% CI) Phase 3 Study population baseline characteristics and times function test results |
 19 Other Phase 3 Considerations “New” sites recruited for Phase 3 to support global adoption Using only subjects from the Phase 2 sites Week 24 had 6MWD p=0.020 and Week 48 had p=0.058 6MWT based on single performance of test Duplicate testing reduces variability Corticosteroid use at new sites not a standard of care ~30% of patients recently started corticosteroids |
 20 Path to Early Approval in U.S. and E.U. Accelerated approval path based on Phase 2 results in-line with FDA guidance Clinical data from randomized Phase 2 studies and long-term studies; well- tolerated Severe unmet need of population and highly active Anticipated first to file Effective patient advocates Rationale for Phase 3 result AND…… Need to explain Phase 3 design and conduct limitations Need to finalize and implement confirmatory study that gives health authorities confidence |
 21 Timeline of Regulatory Events 4Q14 NDA rolling submission commenced with FDA 1Q15 anticipated completion of NDA submission with FDA 2015 expected MAA application for drisapersen with EMA 1H15 initiation of two confirmatory studies to support potential accelerated approval for drisapersen |
 22 Prosensa Acquisition – Attractive Risk/Reward Profile Potential to be financially transformative for BioMarin; Duchenne muscular dystrophy represents our largest potential market opportunity yet Opportunity to leverage BioMarin’s development and commercial capabilities and rare disease business model in a large, untapped market Accretive to operating and GAAP profitability in 2017 with near-term approvals in both U.S. and E.U. if obtained Accretive to operating profitability in 2017 and GAAP profitability in 2018 with near-term approval in U.S. or E.U. if obtained Manageable investment risk for BioMarin; up front purchase price represents roughly 5% of our market capitalization Multiple Paths to Value Creation |
 23 Transaction Specifics Stock purchase at $17.75 per share for total cash consideration of approximately $680 million Two approximately $80 million non-transferrable CVRs payable only on early U.S. approval no later than May 15, 2016 and EMA approval by February 15, 2017 Tender expected to initiate in Q4 2014 and close in Q1 2015 Within 5 days of signing the merger agreement BioMarin will provide Prosensa with an approximately $50 million convertible note. If the merger fails to close for any reason, the note will convert into approximately 4.4 million shares of Prosensa’s stock BioMarin will maintain operations at Prosensa’s headquarters, based in Leiden, The Netherlands and integrate Prosensa personnel from that office Transaction to be funded from BMRN cash ($1.1B at 9/30/14). Anticipate replenishing cash balance |
 24 Prosensa Acquisition Conclusions • Great strategic fit and value creator for BioMarin • Drisapersen has a large body of clinical data that could support early regulatory approval • Leverages BioMarin’s extensive experience getting orphan drugs approved • DMD is one of the largest monogenetic disorders (approx. 75,000 WW) • Leverages our global commercial infrastructure and leadership in orphan disease market • Adds what could be our largest product to a well diversified product portfolio • With early approvals, accretive to operating and GAAP earnings in 2017 • A potentially transformative investment that is risk managed |