35 th Annual J.P. Morgan Healthcare Conference. Jean-Jacques Bienaimé Chairman and Chief Executive Officer BioMarin Pharmaceutical Inc.

Transcription

1 35 th Annual J.P. Morgan Healthcare Conference Jean-Jacques Bienaimé Chairman and Chief Executive Officer BioMarin Pharmaceutical Inc. January 9, 2017

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. 2

3 2017: BioMarin s 20th Year Anniversary Two Decades of Innovation and Productivity >$1.1billion expected product revenue for FY ,200+ global employees 14million units of product manufactured in approved products 3 rd year in a row voted top 10 most innovative Company, according to Forbes 5 products in clinical development 27 congress presentations around the globe in global markets served 20 th year of scientific innovation 118 abstracts accepted at global medical meetings in % increase in revenues from 2006 to years on average from IND to approval for all marketed products 3

4 Five Approved Products and a Robust Clinical Portfolio Commercialized Products Late-stage Development Pipeline Brineura TM for CLN2, or Batten Disease Pegvaliase for Phenylketonuria Vosoritide for Achondroplasia BMN 270 for Hemophilia A BMN 250 for MPS IIIB, or Sanfilippo Type B PHASE 1 PHASE 2 PHASE 3 BLA/NDA/MAA 4

5 Rapid Product Development Track Record Efficient drug development drives strong returns on R&D investment 5 Years 5 Years 3 Years 5 Years 4 Years* IND or CTA Filing 5 years Time to Approval from IND/CTA filing 10 years * If approved on anticipated April 2017 PDUFA date 5

6 Demonstrated Track Record of Consistent Revenue Growth $1,100 $1,150 Vimizim Naglazyme Kuvan Aldurazyme + Other (Revenues in millions) $501 $549 $751 $890 $340- $360 $290- $320 $441 $297 $325 $376 $340- $360 $26 $84 $ E 6

7 Existing Global Infrastructure Generates Revenue Worldwide Will support potential new launches of Brineura in 2017 and Pegvaliase in 2018 Global footprint in 4 key regions representing 68 countries 7

8 Vimizim elosulfase alfa Indication: Morquio A Syndrome (MPS IVA)

9 Vimizim FY 2016 Revenue Guidance $340M-$360M $700M market opportunity based on currently identified patients Over 2000 patients identified New patient identification continues Epidemiology suggests 3000 patients WW Patients Identified Pace of patient identification ,000 1,800 1,650 1,400 1,200 1, Revenues in millions USD $110M $100M $90M $80M $70M $60M $50M $40M $30M $20M $10M Robust Revenue Trajectory 1Q14 Launch through 3Q Q14 2Q14 3Q14 4Q14 1Q15 2Q15 3Q15 4Q15 1Q16 2Q16 3Q16 4Q16E

10 Kuvan sapropterin dihydrochloride Indication: Phenylketonuria (PKU)

11 Newly Acquired Markets Help Drive 14% Y/Y Revenue Growth Kuvan FY 2016 revenue guidance $340M-$360M Significant Worldwide Opportunity ROW territories acquired from Merck 1Q16 EU exclusivity extended through 2024 ROW markets leverage established infrastructure Patient growth 15% Y/Y in NorAm region Y/Y revenue growth of 14% Developing market to prepare for pegvaliase Revenue growth driven by new patients in the US and addition of international markets Revenues in millions USD $100M $90M $80M $70M $60M $50M $40M $30M $20M $10M NorAM ROW 1Q15 2Q15 3Q15 4Q15 1Q16 2Q16 3Q16 4Q16E 11

12 5 Products in Clinical Development Potential approval of Brineura in 2017 and Pegvaliase in 2018 Development Pipeline PHASE 1 PHASE 2 PHASE 3 BLA/NDA/MAA Brineura TM (cerliponase alfa) for CLN2, or Batten Disease Pegvaliase for Phenylketonuria Vosoritide for Achondroplasia BMN 270 for Hemophilia A BMN 250 for MPS IIIB, or Sanfilippo Type B 12

13 Brineura cerliponase alfa BMN 190 Indication: CLN2 Disorder, or Batten Disease

14 Brineura for CLN2 : Our Next Potential Product Launch CLN2 disease results in rapid decline of all functions and death by age years CLN2 Attributes: Patients appear developmentally normal until ~ 3 years old Homogenous Natural Clinical Course of Patients with CLN2 Healthy children score 6 Disease characteristics: seizures language and motor loss dementia blindness and early death Estimated prevalence of approximately 1,200 to 1,600 children (Clinical score) Currently therapy supportive/palliative only (Age in years) 14

15 Effectiveness Demonstrated in Pivotal and Extension Studies All patients treated for 72 weeks or more Change in Motor-Language CLN2 Scores from Baseline to last 300mg dose (>72 weeks) CHANGE IN SCORE (15/23) 65% No Clinical Progression; p = % Responder Rate; p = NUMBER OF SUBJECTS Change in Motor-Language CLN2 Scores from Baseline compared to Natural History at weeks p < Comparison of mean rate of decline to the Natural History rate of decline (2 points/48 weeks) Consistent p value at > 72 weeks 15

16 April 2017 PDUFA Goal Date; Potential US Launch in 2Q17 CHMP decision anticipated 3Q17; potential EU launch 4Q17 EU and US Registrations Under Review Majority of review questions relate to the use of Natural History as a control arm and robustness of a single small study: Comparability of scales between Natural History and clinical study Comparability of populations between Natural History and clinical study Statistical analysis Robustness of response given small data set 16

17 Pegvaliase BMN 165 Target indication: Phenylketonuria (PKU)

18 Pegvaliase: Recent FDA Feedback Solidifies Path Forward Next steps established on requirements for BLA filing Based on recent interactions with the FDA: Phe lowering alone could support a path to approval A more recent data cut will be submitted for regulatory review BLA now planned 2Q17 Next steps planned for MAA submission in the EU: Meeting with EU health authorities to determine regulatory path forward mid-year PKU Market Opportunity: Potentially ~ 5,500 of the ~15,500 diagnosed PKU patients in North America Potentially ~ 18,000 of the ~31,000 diagnosed PKU patients in our ex-noram territories 18

19 Vosoritide BMN 111 Target indication: Achondroplasia

20 Achondroplasia: Most Common form of Dwarfism Achondroplasia In addition to short stature, serious medical complications include: foramen magnum compression sleep apnea bowed legs permanent sway of the lower back spinal stenosis obesity Global market opportunity ~24,000 patients, with ~80% ex-us Children with Achondroplasia Grow an Average of 4cm/year vs. 6cm/year for Average Height Children 20

21 Vosoritide: Return to Normal Growth Rate Observed at 12 months Phase 3 study in achondroplasia initiated December 2016 Strong Phase 2 Results with 15µg/kg/day dose: ~50% increase in growth velocity observed Generally well tolerated over 12 months of dosing Phase 3 Study Design and Next Steps: Randomized, placebo-controlled 12-month treatment study with subsequent long-term open-label extension Ages 5 14, consistent with Phase 2 population Annualized growth velocity as primary endpoint International, multi-site study underway to support global registration Anticipate months to enroll treatment study 21

22 Naglu BMN 250 Target indication: MPS IIIB (Sanfilippo Syndrome, Type B)

23 BMN 250 for MPS IIIB (Sanfilippo Syndrome, Type B) About MPS IIIB: Rapidly progressive pediatric brain disease caused by NAGLU enzyme deficiency resulting in accumulation of heparan sulfate (HS) in the brain Accumulation of HS leads to progressive cognitive decline, loss of developmental milestones, severe hyperactivity, sleep disorders, loss of mobility, and early death BMN 250 is an Innovative Product for MPS IIIB: Leveraging Brineura experience, BMN 250 is an enzyme replacement therapy delivered directly into the CNS via an intracerebroventricular (ICV) access device ICV allows for drugs to bypass the blood brain barrier Delivery of drug into the CSF allows for distribution within the brain 23

24 Near Normalization of Key Marker (HS) and Marker of Downstream Damage (LAMP2) Delivering BMN 250 using ICV Significant reductions in HS needed to reduce tissue damage and potentially improve clinical outcome [% naglu -/- vehicle] Mean ± SEM 0 Total Heparan Sulfate (Brain) **** *** Vehicle BMN 250 naglu -/- naglu -/- ICV IV Vehicle Wild Type [# foci x100 per 4x field] LAMP-2 (Brain) **** Vehicle BMN 250 naglu -/- naglu -/- ICV IV Vehicle Wild Type NOTE: LAMP-2 IHC data for ICV vs. IV analyzed separately ICV-administered BMN 250 significantly reduced pathological GAG accumulation in the brain of mice The equivalent dose of IV-administered BMN 250 did not produce these profound effects in mice 24

25 BMN 250 Reduces HS levels to Normal Range in CSF of MPS IIIB Patients Encouraging biomarker results at lowest dose of 30mg, patients have safely escalated to 100mg Next Steps: Continued enrollment of study Update at WORLD meeting in February BioMarin Confidential For Internal Use Only 25

26 Gene Therapy BMN 270 Target indication: Hemophilia A

27 BMN 270 News Today: Data from high-dose patients since July 2016 update FVIII levels stabilized Mean Annualized Bleed Rate declined 91% for patients previously on prophylactic Factor VIII All patients off steroids ALT levels (liver function) in or around the normal range 27

28 Hemophilia A: Significant Unmet Medical Need Patients experience spontaneous bleeding events even with FVIII replacement therapy* Limitations of prophylactic and on-demand FVIII replacement therapy: Peaks and troughs of FVIII that lead to bleeds Additional FVIII infusions required for break-through bleeds despite adherence to prophylaxis Progression of joint disease leading to pain, decreased mobility and reduced Quality of Life (QoL) Careful planning of physical activities around infusion timing to prevent bleeds Potential development of inhibitors Need for multiple (2-4) FVIII infusions weekly given short half-life (8-16 hours) *(Fischer, 2011, Haemophilia); (Berntorp, 2014)) 28

29 Peaks and Troughs: Primary Limitation of FVIII Replacement Extended half life factor replacement does not eliminate the wide swings in peaks and troughs that result in bleeding episodes Bleeding Risk, Activity and Factor Levels Extended Half-Life Factor Traditional Factor LOWER RISK Factor Level (%) Bleeding Risk Time (Days) Source: Role of New Prolonged Half-Life Clotting Factors in Hemophilia (NHF 2015) HIGH RISK 29

30 BMN 270: FVIII Levels Stabilized and Maintained out to 50 weeks Baseline FVIII activity for all subjects at study start was <1% of normal level Weeks N= Normal FVIII Range: 50%- 150% 30

31 BMN 270 Effectiveness Maintained out to 50 Weeks Baseline FVIII activity for all subjects in BMN 270 study was <1% of normal level High-dose Subject # FVIII level (%) at last update July 6 Most recent week of observation FVIII level (%) at most recent observation* *Data as of Dec. 9 31

32 Prior to Treatment with BMN 270 Annualized Bleeding Rate (ABR) and Annualized Number of FVIII Infusions are Significant Mean ABR (no. of episodes/year) Mean ABR for 6 prophylactic subjects in high dose cohort Mean Annualized number of FVIII Infusions (no. of FVIII infusions/year) Before BMN 270* Before BMN 270* Mean Annualized Number of FVIII Infusions for 6 prophylactic subjects in high dose cohort * Obtained from medical records 32

33 Annualized Bleeding Rate (ABR) and Annualized Number of FVIII Infusions Declines Dramatically with BMN 270 Treatment Mean ABR (no. of episodes/year) Mean ABR for 6 prophylactic subjects in high dose cohort 16.3 Mean Annualized Number of FVIII Infusions for 6 prophylactic subjects in high dose cohort % Reduction 98% Reduction 1.5 Before BMN 270* After BMN 270** Before BMN 270* After BMN 270** 5 of 6 had no bleeds requiring FVIII use after week 2 Mean Annualized number of FVIII Infusions (no. of FVIII infusions/year) of 6 had no FVIII infusions after week 2 * Obtained from medical records **Rates after BMN 270 were based on data after week 2 through last follow-up visit 33

34 Liver Function Tests (ALT) in or Around Normal Range Since WFH all ALT results have improved and all patients are off steroids High-dose Subject# Peak ALT level ALT (U/L); (ULN = 43 (U/L)) Last ALT level* Last ALT Level Status Normal Normal Normal Normal Normal <1.1 ULN Normal *Data as of Dec. 9 34

35 BMN 270: Moving to Registration-enabling Study News Today on High-dose patients: FVIII levels stabilized Mean Annualized Bleed Rate declined 91% for patients previously on prophylactic Factor VIII All patients off steroids ALT levels (liver function) in or around the normal range Next Steps: Begin potentially registration-enabling Phase 2b in 3Q17 Complete evaluation of lower dose without prophylactic steroids Commission gene therapy manufacturing facility mid

36 Four Pillars of Growth Driving Value Strong and Growing Base Business: >$1.1B from Existing Products for FY 2016 Two Potential Near-term Launches: Brineura 2017; Pegvaliase 2018 Two Potential $1 Billion Opportunities on the Horizon: Vosoritide for Achondroplasia; BMN 270 for Hemophilia A Turning the Corner Towards Profitability: 2017 GAAP Loss/ Expect non-gaap Breakeven or Better in 2017 * For a detailed description about our use of non-gaap net income, and the methodology used in calculating such measure, please see the discussion under the heading Non-GAAP Information included with our most recent quarterly earnings press release, which can be found at: 36

37 THANK YOU 37