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BioMarin Pharmaceutical Inc.
2Q19
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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.
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7 Approved Products Targeted to Deliver $2B in Revenues in 2020
Commercialized Products
Vosoritide for Achondroplasia
Valoctocogene Roxaparvovec for Hemophilia A (under AA scenario)
Tralesinidase Alfa for MPS IIIB, or Sanfilippo Type B
PHASE 1 PHASE 2 PHASE 3 BLA/NDA/MAAProduct Development Pipeline
IND/CTA
BMN 290 for Friedreich’s Ataxia
BMN 307 Gene Therapy for PKU
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Demonstrated Track Record of Growing Revenues
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019E
$26
$325$297
$122
$441$376
$84
$501$549
$751
$890
$1,117
$1,491
$530-
$570
$350-
$380
$420-
$460
$1,313
(Revenues in millions)
Palynziq
Brineura
Vimizim
Naglazyme
Kuvan
Aldurazyme + Other
$70- $100
$55- $75
2019 FY Guidance
$1,680 - $1,750
Commercial base business expected to drive 15%+ top-line growth Y/Y in 2019
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Late-stage Product Highlights and Anticipated Near-term Catalysts
• EU approval received May 6, 2019
• US launch drives 414 patients on reimbursed Palynziq at end of 1Q19
• 2019 FY revenues expected to be between $70M-$100M
Vosoritide• Global Phase 3 enrolled; data expected YE 2019
0-5 year-old study underway:
• Cohort 1 (24 to 60 month olds) nearly finished enrolling;
• Cohort 2 (6 to 24 month olds) enrolling
(Adult phenylketonuria)
(achondroplasia)
Valoctocogene
Roxaparvovec
• Manufacturing campaigns and enrollment for AA filing completed
• Complete enrollment in Phase 3 for “Full” Approval anticipated 3Q19
• Accelerated Approval filing decision tracking to 2H19(severe Hemophilia A)
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Valoctocogene
Roxaparvovec
• Manufacturing campaigns and enrollment for AA filing completed
• Complete enrollment in Phase 3 for “Full” Approval anticipated 3Q19
• Accelerated Approval filing decision tracking to 2H19(severe Hemophilia A)
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ValRox 2019: Key Development/Regulatory/Commercial Activities Underway
• Accelerated Approval Filing
• Full Approval Filing
• Regulatory Agency Interactions and Timelines in US and EU
• Pricing/Reimbursement: based on Clinical Outcomes and Current Established Costs
• Commercial Pre-launch Preparations and Readiness
Focus on components for both expedited and full registrations to support potential approval(s) and launch
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ValRox 2019: Accelerated Approval Elements Tracking to Plan
Accelerated Approval considerations and activities underway:
• Phase 3 study cohort required for AA filing enrolled
• FDA considerations based solely on FVIII above 40 IU/dL through 12 months
• Manufacturing campaigns required for AA filing completed
• Longer-term data from ongoing Phase 2 study anticipated by June 7
• Chromogenic FVIII assay accepted as appropriate measure of activity levels with valrox to support accelerated approval
Key activities and read-outs to enable Accelerated Approval filing decision 2H19
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FVIII Activity Levels in Normal Range with Chromogenic Assay at 1-yearValrox Phase 1/2 data conforms to regulatory requirements for expedited registration
The upper and lower box bounds represent 25th and 75th percentiles. The whisker lines represent the minimum and maximum values.
Expedited Registration:
Powered based on Phase 1/2
Valrox 6e13 vg/kg dose results to 52 weeks
50%-150% “normal range”
> 40% “non-hemophilic” range;
threshold for Accelerated Approval
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Sustained Reduction of Annualized Bleed Rates 2-years Post Valrox TreatmentValrox 104 week Phase 1/2 ABR data superior to Standard of Care
ABR results with 6e13 dose through week 104
% Patients Bleed Free
97% REDUCTION in MEAN ABR
Baseline Year 1 Year 2
14% 71% 86%
All patients off prophylaxis
100% resolution in target joints
As presented at WFH, May 22, 2018
16.5
0 0
16.3
0.9 0.50
5
10
15
20
Pre-infusion Post-infusion(52 weeks)
Post-infusion(104 weeks)
AB
R (
ep
iso
de
s/ye
ar)
median mean
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Valrox Substantially Improves Quality of LifeValrox 104 week Phase 1/2 QoL data superior to Standard of Care
As presented at WFH, May 22, 2018
Grey line indicate distribution based minimally clinical important difference (MCID) at lower threshold
* Pocoski J et al., 2014
Me
an
Ch
an
ge
in
Ha
em
o-Q
oL
-A T
ota
l S
co
re
6e13 vg/kg cohort
4e13 vg/kg cohort
Spinart result at 3 years*
0
2
4
6
8
10
12
14
16
18
Week 16 Week 28 Week 52 Week 78 Week 104
7.2
4.76.3
3.8
13.4 12.9
9.6
16.617.3
• QOL improvement
observed in all 6 domains:
‒ Consequences of
Bleeding
‒ Emotional Impact
‒ Physical Functioning
‒ Role Functioning
‒ Treatment Concern
‒ Worry
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Hemophilia B: Sustained FIX Levels Result in Significant Bleed Control8 year follow up from Dr. Amit Nathwani’s FIX gene therapy study in subjects with severe Hemophilia B
Nathwani et al. ASH 2018
0 2 4 6 8
0
2
4
6
Years
FIX
(%
of
no
rmal)
Low (N=2) Mid (N=2) High (N=6)
P<0.0001
5.1 1.4 IU/dL2.3 0.3 IU/dL1.9 0.6 IU/dL
FIX activity levels (mean, SD):
16.5 10
All-
Pre
All-
Post
HD-P
re
HD-P
ost
0
10
20
30
40
An
nu
alised
ble
ed
rate
(N
o/Y
ear)
p = 0.002 p = <0.001
2.2 2 21.9 11 2.3 2
Annualized bleed rateFIX levels through years 6 and 8
(Through year 6) (Through year 8)
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AAV Durability for the Life of Canine Subjects as Measured by Chromogenic Assay
BioMarin data
FVIII expression post AAV gene therapy in canine hemophilia
Chromogenic FVIII activity measured using a canine normal pooled plasma standard. Source: Batty, P. et al unpublished data
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Similar FVIII Expression Profile seen with AAV5 in Non-human Primates
BioMarin data
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 2000
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
Study Day
FV
III P
rote
in (
ng
/mL
)
• Independent of capsids, promoter, transgenes• Dose-dependent
Non-human primates
(cynomolgus monkeys)
* Immunosuppression regimen included in study protocol
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Circular Episomes Persist 1 Year After Treatment; ASGCT data May 2019
• Circular episomes have been shown to be the long-lived gene-expressing form in multiple pre-clinical models of AAV gene therapy
• BioMarin assays can detect structural forms of FVIII transgene at single molecule sensitivity, using blood cells as a non-invasive alternative to liver biopsies
• Long term FVIII transgene from a liver-directed promoter is associated with circular, episomal forms inside cells• Past the time of red cell clearance, vector persists in peripheral blood mononuclear cells as circular episomes• We speculate that similar patterns of vector loss from the liver will depend on the rate of liver cell turnover
Weeks after infusion of BMN 270
Cellular Episomes Vector Cleared Late through Senescence 52 week whole blood DNA is primarily episomes in PBMCs
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ValRox 2019: Full Approval Elements Tracking to Plan
Full Approval considerations and activities with GENEr8-1 Phase 3 study:
• 95% of subjects interested in 6e13 dose study
• N=130, goal to prove “Superiority” in bleed reduction vs. Standard of Care (prophylaxis)
• 52-week study, endpoints include reduction in bleeds and FVIII usage
• Global Phase 3 study underway in 13 countries
• Enrollment completion expected 3Q19
Key activities to support full approval path forward
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ValRox 2019: Filing Agreements Reached with Regulatory Authorities
Key agreements have been reached regarding plans for marketing application submissions in US and EU, including:
• Success criteria for Phase 3 study Interim Analysis to support US Accelerated Approval
• Structure, format, and content for all modules (CMC, Nonclinical, and Clinical)
• Data-cuts and size of the safety database
• Final results from Phase 3 study to serve as confirmatory evidence for Full Approval
Next Steps:
• Meetings with US and EU regulators planned for mid-2019, following availability of Phase 3 study interim analysis and Phase 2 study 3-year data
• Decision to pursue accelerated marketing application on track for 2H19
Breakthrough Designation and PRIME status have facilitated frequent interactions with US and EU regulators
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ValRox 2019: Pricing & Reimbursement will be Based on Clinical Outcomes Valrox targets substantial improvement over Standard of Care
High Unmet Needs with Current Standard of Care
Recurrent joint bleeds
Deterioration of target joints
Burdensome weekly infusions
Limited physical activity
Peaks and troughs
High costs for lifetime therapy
Valrox Cumulative Value Over Standard of Care
Elimination of bleeds
Resolution of target joints
One-time infusion
More active lifestyle
Meaningful QOL improvements
Cost offsets of millions over lifetime
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Recent Survey: Speedy Uptake >40% Market Share in Severe Population in 5 Years
• Hematologists anticipate robust uptake; among eligible severe hemophilia patients (see Q18) ~25% immediately after approval and ~45% after 5 years
• Of note, ~45% (severe) and ~30% (moderate) penetration rates are higher than our estimates of 15-30% in hemophilia A (Valrox, SPK-8011)
• Hematologists also projected gene therapy use among moderate hemophilia patients
Hemophilia A
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Global Hemophilia A Market in 2016 was $8.4B1
Estimated WAC pricing for Hemlibra in non-inhibitor adult patients is between $600K - $800K per year2
Fully-compliant, WAC pricing for FVIII replacement in adults is $403K-$674K per year 3
An Estimated 117K Hemophilia A Patients in our Territories 3
NORAM total: ~18,000
LATAM total: ~22,000
EUMEA total: ~64,000
APAC: ~13,000
1 Evaluate Pharma; 2 PriceRx IHA Global insight Oct. 2015-Oct. 2016 (WAC price reflects cost of Factor VIII replacement for an adult on prophylaxis)
2 Based on WAC price of $99.20 per mg $482K/year for a 58 kg subject; Centers for Disease Control and Prevention (CDC) estimates the average adult American male weighs >90 kg
3 EPI Data from 2016 WFH Annual Survey; NHF website: http://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A;
Hemophilia A Severity
Source: WFH 2016
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Multiple Lifecycle Management Opportunities Exist to Capture Majority of 117K Hemophilia A Patients in our Territories
Goal to expand into additional Hemophilia A patient subpopulations over time
• All levels of
severity
• All Ab-status
• All inhibitor status
AAV5 Ab+
All prophy
subjects
Adolescents
AAV5 Ab free, >
18 y/o, severe
• AAV5 Ab free, >
18 y/o, severe
• AAV5 Ab+
• All prophy
subjects
• Adolescents
AAV5 Ab free, >
18 y/o, severe
Valoctocogene
Roxaparvovec
Initial label
Valoctocogene
Roxaparvovec
Future label
~30,000 patients
~50,000 patients
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Annual Valrox Market OpportunityAverage price based on cost of either rFVIII or Hemlibra for a severe Hemophilia A patient
Patients Treated/ Year
Average Price: $1M(1)
Average Price: $2M(2)
Average Price: $3M
1,000 patients $1B $2B $3B
2,000 patients $2B $4B $6B
3,000 patients $3B $6B $9B
4,000 patients $4B $8B $12BBMRN current manufacturing capacity of 4,000 patients; easily scales to 5,000 patients
Initial target market: 30,000 (severe Hem A; 18 y/o +; AAV5 Ab free)
(1) 1.5 years of Hemlibra (non-inhibitor price)
(2) 3 years of Hemlibra (non-inhibitor price)
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In-house Manufacturing Capabilities to Support Seamless Launch
FULLY INTEGRATED VECTOR PRODUCTION FACILITY
• Facility Design Vetted with Health Authorities
• Single Use Technology Throughout
• Multi-Product Production
• Supports Multiple 2000L Bioreactors
• Supports 4000 Patients/year at Highest Dose
• ISPE 2018 Facility of the Year – Project Execution
Biologics Facility Gene Therapy FacilityBioMarin’s
Ready to supply 4000-5000 patients with commercial valrox at launch; plans for next GT facility being finalized
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Vosoritide(achondroplasia)
• Global Phase 3 enrolled; data expected YE 2019
0-5 year-old study underway:
• Cohort 1 (24 to 60 month olds) nearly finished enrolling
• Cohort 2 (6 to 24 month olds) enrolling
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About AchondroplasiaSpontaneous mutation that occurs in 80% of cases from parents of average stature
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
~ 24,000 children with achondroplasia in our global territories
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Growth Characteristics in Achondroplasia
AchondroplasiaAverage stature
Hoover Fong et a. J Clin. Nut. 2008
4 cm/year 6 cm/year
Children with Achondroplasia Grow an Average of 4cm/year
vs. 6cm/year for Average Height Children
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DIAGNOSIS HEIGHT SD(Z-score)
ACHONDROPLASIA -6.0GH DEFICIENCY -2.7
IDIOPATHIC SHORT STATURE -2.6
TURNER SYNDROME -2.8
SMALL FOR GESTATIONAL AGE
-2.5
NOONAN SYNDROME -2.3
Magnitude of Height Deficits in Various Short Statural Conditions
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Durable Growth Sustained through 42-months with Vosoritide 15µg/kg Dose
42 Month Additional Height Gained is 5.7cm with Vosoritide
Sustained elevation of AGV shown in sequential 6-month time periods in ongoing Phase 2 study
Average Stature AGV
Baseline ACH AGV
Vosoritide (15µg/kg) n=8
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Executing 4 Pillar Strategy to Demonstrate Improved Clinical Outcomes with Vosoritide
Comprehensive Global Development Program:
• Phase 3: Placebo-controlled, global trial (over)enrolled; 121 subjects enrolled
• Phase 2: (5 to 14 years) demonstrating additional height gain of 5.7cm at 42 months
• Phase 2: (0 to <5 years) Cohort 1 (24 -60 months) enrolled; Cohort 2 (6 -24 months) underway and generally well-tolerated in early dosing with no symptomatic AEs identified; Cohort 3 to begin enrollment once Cohort 2 complete
• Large contemporaneous Natural History Data to Assess Final Adult Height
NEXT STEPS: Phase 3 data YE 2019
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(Adult phenylketonuria)
• EU approval received May 6, 2019
• US launch drives 414 patients on reimbursed Palynziq at end of 1Q19
• 2019 FY revenues expected to be between $70M-$100M
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Palynziq Approved in the EU May 6; Preparing for Launch 2H19
PKU patients defined as patients diagnosed through newborn screening; EUMEA includes Europe, Turkey, Russia and Middle East
Market Attributes:
• Large initial commercial market of 5,800 in-clinic PKU patients aged 16 and older
• 3 years of direct experience working with PKU community to prepare for launch
• Anticipate meaningful revenue in EU starting 2020 following usual pricing and reimbursement process by country
Out of Clinic On Kuvan In-Clinic
Total: 18,000
~500
~11,700
~5,800
PKU Patients 16 years + in EUMEA
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Strong Initial US Launch Continues; Metrics as of March 31, 2019PKU represents BioMarin’s largest US patient population opportunity
>11,000 adult patients with PKU, 3,900 actively managed in-clinic
Sites with ≥1
complete enrollment
Patients on
reimbursed Palynziq
Clinical Study
Patients
Formerly Naïve
Patients
+
Patients enrolled but not yet
reimbursed/on therapy
Breadth and depth of adoption
across key clinics, both clinical trial
sites and naïve clinics
Positive payer coverage at launch
leading to strong uptake of
reimbursed patients
Leading indicators point toward
continued uptake acceleration in
2019
89
414 = 136 278
140
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3 Year Durability with Palynziq Strengthens EU Plans< 600 µmol/L - EU PKU guideline recommendation
< 360 µmol/L - US guideline recommendation< 120 µmol/L - physiologically normal
Proportion of Subjects Reaching Blood Phe Threshold over Time(doses up to 60mg/day) (n=285)
42%
57%
71% 74%
29%
46%
63%67%
22%
35%
54%59%
6 months 12 months 24 months 36 months
≤600 umol/L ≤360 umol/L ≤120 umol/L
Subjects reflect general adult PKU population with mean baseline blood Phe 1233µmol/L
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What’s Next?
BioMarin’s Formula for “Medium Rare” Disease Drug Development
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Our Enriched Approach for Speed and Success4 Key Criteria Guide Discovery and Development at BioMarin
• IND to approval in 4-6
years for 5 out of 7
products
• Hem A, PKU, MPS:
Rapidly gauge efficacy with
relevant endpoints
• Gene therapy to restore
FVIII expression in Hem A
and PAH activity in PKU
• Hem A, PKU, CLN2,
MPS I, IVA, VI,
achondroplasia
• High unmet need and rapid
development
• Diseases with genetic
mechanisms
• Target epicenters and drive for
normalization
• Discern outcomes through
sensitive endpoints
3
FVIII
Phe
Phe
Tyr
PAHx
1
2
3
4
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BMN 307: Leveraging Our Leading Gene Therapy Capabilities
Pre-existing
immunity
Vector
optimization
Expression
Manufacturing
Tissue
tropism
AAV BMRNAAV9
Improved tissue tropism with novel
BMRN AAVs – muscle example
Core gene therapy expertise
across 5 domains
1
2
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5
Reference: Data on file, BioMarin (2018)
Novel BMRN AAVs with less
susceptibility to pre-existing immunity
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BMN 307 and the PKU Model Used for Development
Validated mouse model of PKU (the ENU2 model)
‒ Mice have no detectable PAH catalytic activity and high Phe levels
Model recapitulates many aspects of the human PKU phenotype, including:
‒ High plasma/tissue Phe
‒ Reduced neurotransmitters
PKU mice also have a light coat color
Acts as a readily detectable biomarker of
therapeutic response
BMN 307: Liver-directed gene therapy (AAV5 PAH)
IND filing in 2H19 (Commercial scale material available in 2H19)
ENU2WT
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Lifetime Phe Correction seen in Treated PKU Mice with BMN 307; IND 2H19
Reference: Data on file, BioMarin (2018)
Phenylalanine reductions seen in ENU2 mice
Phe in µM
2 weeks
ENU2 vehicle
ENU2 + AAV5 muPAH
WT vehicle
ENU2 + AAV5 PAH
• AAV5-PAH
normalizes Phe in
ENU2 mice
• Levels
indistinguishable
from WT after 2
weeks
• Efficacy
sustained at 80
weeks
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2019 Financial Guidance
Revenue Guidance ($ in millions)
Item 2019 Guidance
Total BioMarin Revenues $1,680 to $1,750
Vimizim Net Product Revenue $530 to $570
Kuvan Net Product Revenue $420 to $460
Naglazyme Net Product Revenue $350 to $380
Palynziq Net Product Revenue $70 to $100
Brineura Net Product Revenue $55 to $75
Selected Income Statement Guidance ($ in millions, except percentages)
Item 2019 Guidance
Cost of Sales (% of Total Revenue) 20% to 21%
SG&A Expense $650 to $690
R&D Expense $740 to $780
Non-GAAP Net Income $130 to $170
GAAP Net Loss $(45) to $(85)
15% Revenue Growth Anticipated Y/Y in 2019; and $2B in Revenue Targeted in 2020
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THANK YOU
as of May 13, 2019