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35th Annual J.P. Morgan Healthcare Conference
Jean-Jacques BienaiméChairman 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.
3
2017: BioMarin’s 20th Year Anniversary Two Decades of Innovation and Productivity
>$1.1billion
expected product revenue for FY 2016
2,200+global employees
14million
units of product manufactured in 2016
5approved products
3rdyear in a row voted top 10 most innovative Company, according to Forbes
5products in clinicaldevelopment
27congress presentations around the globe in 2016
68global markets served
20thyear of scientific innovation
118abstracts accepted at global medical meetings in 2016
1300%increase in revenues from 2006 to 2016
5years on average from IND to approval for all marketed products
4
Five Approved Products and a Robust Clinical Portfolio
Commercialized Products
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
Late-stage Development Pipeline
5
5 Years
IND or CTA Filing 5 years
5 Years
3 Years
5 Years
Rapid Product Development Track Record Efficient drug development drives strong returns on R&D investment
Time to Approval from IND/CTA filing 10 years
4 Years*
* If approved on anticipated April 2017 PDUFA date
6
$26 $84
$122
$297 $325
$376 $441
$501 $549
$751
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016E
VimizimNaglazymeKuvanAldurazyme + Other
$290-$320
$340-$360
Demonstrated Track Record of Consistent Revenue Growth
(Revenues in millions)
$890
$1,100 –$1,150
$340-$360
7
Existing Global Infrastructure Generates Revenue WorldwideWill support potential new launches of Brineura in 2017 and Pegvaliase in 2018
Global footprint in 4 key regionsrepresenting 68 countries
Vimizimelosulfase alfa
Indication:Morquio A Syndrome (MPS IVA)
9
Vimizim FY 2016 Revenue Guidance $340M-$360M
Over 2000 patients identified• New patient identification continues
• Epidemiology suggests 3000 patients WW
1Q14 2Q14 3Q14 4Q14 1Q15 2Q15 3Q15 4Q15 1Q16 2Q16 3Q16 4Q16E
Reve
nues
in m
illio
ns U
SD
$10M
$20M
$30M
1
14
25
$40M
Robust Revenue Trajectory1Q14 Launch through 3Q16
37
2010 2011 2012
Patie
nts I
dent
ified
500
1000
1500
8001,000
1,200
2000
2013
Pace of patient identification
1,400
2014 20150
1,650
1,800
$50M
$60M
$70M
5154
65 59
73
107
$80M
$90M$100M$110M
81
2016
2,000
$700M market opportunity based on currently identified patients
79-99
Kuvansapropterin dihydrochloride
Indication:Phenylketonuria (PKU)
11
Newly Acquired Markets Help Drive 14% Y/Y Revenue GrowthKuvan 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
1Q15 2Q15 3Q15 4Q15
Reve
nues
in m
illio
ns U
SD
$10M
$20M
$30M
$40M
Revenue growth driven by new patients in the US and addition of international markets
$50M
$60M
$70M
50
6064 65
1Q16
77
2Q16
90
$80M
$90M
$100M
17
60
22
68
ROW
NorAM
3Q16
91
20
71
82-102
4Q16E
12
5 Products in Clinical Development
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
PHASE 1 PHASE 2 PHASE 3 BLA/NDA/MAA
Development Pipeline
Potential approval of Brineura in 2017 and Pegvaliase in 2018
Brineuracerliponase alfa
BMN 190
Indication:CLN2 Disorder, or Batten Disease
14
CLN2 Attributes:
• Patients appear developmentally normal until ~ 3 years old
• Disease characteristics: • seizures• language and motor loss • dementia • blindness and early death
• Estimated prevalence of approximately 1,200 to 1,600 children
• Currently therapy supportive/palliative only
CLN2 disease results in rapid decline of all functions and death by age 10-12 years
(Age in years)
(Clin
ical
sco
re)
Healthy children score 6
Homogenous Natural Clinical Course of Patients with CLN2
Brineura for CLN2 : Our Next Potential Product Launch
15
Effectiveness Demonstrated in Pivotal and Extension Studies
3
5
13
2
0 2 4 6 8 10 12 14
-2
-1
0
1
NUMBER OF SUBJECTS
CH
ANG
E IN
SC
OR
E
(15/23) 65% No Clinical Progression; p = 0.0002
87% Responder Rate; p = 0.0002
Change in Motor-Language CLN2 Scores from Baseline to last 300mg dose (>72 weeks)
Change in Motor-Language CLN2 Scores from Baseline compared to Natural History at 48-81 weeks
p <0.0001 Comparison of mean rate of decline to the Natural History rate of decline (2 points/48 weeks)Consistent p value at > 72 weeks
All patients treated for 72 weeks or more
16
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
April 2017 PDUFA Goal Date; Potential US Launch in 2Q17CHMP decision anticipated 3Q17; potential EU launch 4Q17
PegvaliaseBMN 165
Target indication: Phenylketonuria (PKU)
18
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
Pegvaliase: Recent FDA Feedback Solidifies Path ForwardNext steps established on requirements for BLA filing
VosoritideBMN 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
21
Vosoritide: Return to Normal Growth Rate Observed at 12 months
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 12-18 months to enroll treatment study
Phase 3 study in achondroplasia initiated December 2016
NagluBMN 250
Target indication: MPS IIIB (Sanfilippo Syndrome, Type B)
23
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
BMN 250 for MPS IIIB (Sanfilippo Syndrome, Type B)
24
Near Normalization of Key Marker (HS) and Marker of Downstream Damage (LAMP2) Delivering BMN 250 using ICV
0
50
100ICVIV
Mean ± SEM
[% n
aglu
-/- v
ehic
le]
Vehicle naglu-/- naglu-/-
BMN 250
Total Heparan Sulfate (Brain) ****
***
VehicleWild Type
Significant reductions in HS needed to reduce tissue damage and potentially improve clinical outcome
0
2
4
6ICVIV
LAMP-2 (Brain)
VehicleWild Type
Vehicle naglu-/- naglu-/-
BMN 250[#
foci
x10
0 pe
r 4x
field
]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
25BioMarin Confidential – For Internal Use Only
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
Gene TherapyBMN 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
Hemophilia A: Significant Unmet Medical NeedPatients 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
Bleeding Risk, Activity and Factor Levels
Source: Role of New Prolonged Half-Life Clotting Factors in Hemophilia (NHF 2015)
Time (Days)
90
80
70
60
50
40
30
20
10
00 1 2 3 4 5 6 7 8 9 10 11 12
Fact
or L
evel
(%)
Traditional Factor
Blee
ding
Ris
k
LOWER RISK
HIGH RISK
Extended Half-Life Factor
Extended half life factor replacement does not eliminate the wide swings in peaks and troughs that result in bleeding episodes
Weeks
N=
NormalFVIII
Range:50%-150%
BMN 270: FVIII Levels Stabilized and Maintained out to 50 weeksBaseline FVIII activity for all subjects at study start was <1% of normal level
30
BMN 270 Effectiveness Maintained out to 50 Weeks
High-doseSubject #
FVIII level (%)at last update
July 6
Most recent week of
observation
FVIII level (%) at most recent
observation*
1 89 50 121
2 219 42 133
3 271 40 222
4 12 41 16
5 133 40 175
6 69 38 77
7 79 34 62
*Data as of Dec. 9
Baseline FVIII activity for all subjects in BMN 270 study was <1% of normal level
31
Prior to Treatment with BMN 270 Annualized Bleeding Rate (ABR) and Annualized Number of FVIII Infusions are Significant
Mean ABR for 6 prophylactic subjects in high dose cohort
Mean Annualized Number of FVIII Infusions for 6 prophylactic subjects in high dose cohort
Before BMN 270* Before BMN 270*
16.3 136.7
Mea
n An
nual
ized
num
ber o
f FVI
IIIn
fusio
ns (n
o. o
f FVI
II in
fusio
ns/y
ear)
Mea
n AB
R (n
o. o
f epi
sode
s/ye
ar)
* Obtained from medical records 32
Annualized Bleeding Rate (ABR) and Annualized Number of FVIII Infusions Declines Dramatically with BMN 270 Treatment
After BMN 270** After BMN 270**
91% Reduction 98% Reduction136.7
Mean ABR for 6 prophylactic subjects in high dose cohort
Mean Annualized Number of FVIII Infusions for 6 prophylactic subjects in high dose cohort
1.5 2.9
5 of 6 had no bleeds requiring FVIII use after week 2
5 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
16.3
Mea
n An
nual
ized
num
ber o
f FVI
IIIn
fusio
ns (n
o. o
f FVI
II in
fusio
ns/y
ear)
Mea
n AB
R (n
o. o
f epi
sode
s/ye
ar)
Before BMN 270* Before BMN 270*
33
Liver Function Tests (ALT) in or Around Normal Range
High-doseSubject#
ALT (U/L); (ULN = 43 (U/L))
Peak ALT level Last ALT level*Last ALT Level
Status
1 60 15 Normal
2 95 16 Normal
3 82 42 Normal
4 87 33 Normal
5 43 38 Normal
6 81 45 <1.1 ULN
7 66 27 Normal
Since WFH all ALT results have improved and all patients are off steroids
*Data as of Dec. 9 34
BMN 270: Moving to Registration-enabling Study
Next Steps:• Begin potentially registration-enabling Phase 2b in 3Q17• Complete evaluation of lower dose without prophylactic steroids• Commission gene therapy manufacturing facility mid-2017
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
35
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: http://investors.biomarin.com/2016-10-27-BioMarin-Announces-Third-Quarter-2016-Financial-Results
37
THANK YOU