BioMarin Pharmaceutical Inc - Jean-Jacques Bienaimé Chairman and Chief Executive Officer
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37th Annual J.P. Morgan Healthcare Conference
Jean-Jacques Bienaimé
Chairman and Chief Executive Officer
BioMarin Pharmaceutical Inc.
2019
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
News Today: Progress of 3 Transformative Products Anticipated in 2019
Valoctocogene • Enrollment complete for Accelerated filing requirements (new!)
Roxaparvovec • Accelerated Approval filing decision tracking to 2H19
(severe Hemophilia A)
• CHMP opinion anticipated 1Q19; Potential EU approval 2Q19 (new!)
• 2019 FY revenues expected to be between $70M-$100M (new!)
(Adult phenylketonuria)
• Global Phase 3 enrolled; data expected YE 2019
Vosoritide
• 0-5 y/o study enrollment on track and generally well-tolerated in early
(achondroplasia) dosing (new!)
3
7 Approved Products Expected to Deliver $2B in Revenues in 2020
Palynziq approved 2Q18 by FDA, potential EU approval 2Q19
Commercialized Products
Product Development Pipeline BLA/NDA/MAA
IND/CTA PHASE 1 PHASE 2 PHASE 3
Vosoritide for Achondroplasia
Valoctocogene Roxaparvovec for Hemophilia A (under AA)
Tralesinidase Alfa for MPS IIIB, or Sanfilippo Type B
BMN 307 Gene Therapy for PKU
BMN 290 for Friedreich’s Ataxia
4
Demonstrated Track Record of Consistent and Growing Revenues
Expect commercial base to drive 15%+ top-line growth through 2020 followed by acceleration
$1,470 -
$1,530
$35-
Brineura $55
Vimizim $1,313
Naglazyme $460-
$1,117 $500
Kuvan
Aldurazyme + Other
$890
(Revenues in millions)
$751 $325-
$355
$549
$501
$441
$376 $440-
$297 $325 $480
$122
$84
$26
5
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018E• CHMP opinion anticipated 1Q19; Potential EU approval 2Q19 (new!)
• 2019 FY revenues expected to be between $70M-$100M (new!)
(Adult phenylketonuria)Strong Initial US Launch Continues; Metrics as of December 31, 2018 (new!)
PKU represents BioMarin’s largest US patient population opportunity
>11,000 adult patients with PKU, 3,900 actively managed in-clinic
Breadth and depth of adoption
across key clinics, both clinical trial
72
sites and naïve clinics Sites with ≥1
complete enrollment
Positive payer coverage at launch
leading to strong uptake of
252 = 112 + 140
reimbursed patients Patients on Clinical Study Formerly Naïve
reimbursed Palynziq Patients Patients
Leading indicators point toward
continued uptake acceleration in 154
2019
Patients enrolled but not yet
reimbursed/on therapy
73 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)
71% 74%
67%
63%
57% 59%
54%
46%
42%
35%
29%
22%
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 8Palynziq CHMP Opinion Anticipated 1Q19 (new!)
Potential EU approval 2Q19
Adult PKU Patients in Europe and Turkey
EU Market Attributes:
• Large initial commercial market of
4,900 in-clinic adult PKU patients
• 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
PKU patients defined as patients diagnosed through newborn screening 9• Global Phase 3 enrolled; data expected YE 2019 Vosoritide • 0-5 y/o study enrollment on track and generally well-tolerated in early (achondroplasia) dosing (new!)
About Achondroplasia
Spontaneous 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
11Growth Characteristics in Achondroplasia
Children with Achondroplasia Grow an Average of 4cm/year
vs. 6cm/year for Average Height Children
Achondroplasia
Average stature
4 cm/year 6 cm/year
Hoover Fong et a. J Clin. Nut. 2008
12Magnitude of Height Deficits in Various Short Statural Conditions
DIAGNOSIS HEIGHT SD
(Z-score)
ACHONDROPLASIA -6.0
GH DEFICIENCY -2.7
IDIOPATHIC SHORT STATURE -2.6
TURNER SYNDROME -2.8
SMALL FOR GESTATIONAL -2.5
AGE
NOONAN SYNDROME -2.3
13Durable Growth Sustained through 42-months with Vosoritide 15µg/kg Dose
42 Month Additional Height Gained is 5.7cm with Vosoritide
Average Stature AGV
Baseline ACH AGV
Vosoritide (15µg/kg) n=8
Sustained elevation of AGV shown in sequential 6-month time periods in ongoing Phase 2 study
14Executing 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 toValoctocogene • Enrollment complete for Accelerated filing requirements (new!) Roxaparvovec • Accelerated Approval filing decision tracking to 2H19 (severe Hemophilia A)
Valrox Targets Substantial Improvement over Standard of Care in Hemophilia A
High Unmet Needs with Current Standard of Care Valrox Cumulative Value Over Standard of Care
Recurrent joint bleeds Elimination of bleeds
Deterioration of target joints Resolution of target joints
Burdensome weekly infusions One-time infusion
Limited physical activity More active lifestyle
Peaks and troughs Meaningful QOL improvements
High costs for life Cost offsets of millions over lifetime
17ValRox 2019: Key Anticipated Milestones
Phase 1/2 data with 6e13 dose
• 3-year update “mid-year” at a key medical meeting; potential top-line data update prior to that
• Data to be included in expedited review package with goal of continued hemostasis control
Phase 3 with 6e13 dose
• Powered to demonstrate superiority vs. Standard of Care
• Enrollment completion (includes 6-month run-in; N=130) expected in the third quarter
• Regulatory requirements for durability for full approval will be established over the year following dosing
Accelerated Approval Pathway
• AA filing decision tracking to 2H19 and will include cohort of Phase 3 subjects already enrolled
• Regulatory requirements for durability for AA will be established within one year following dosing in a
smaller subset of patients from Phase 3 cohort
• Comprehensive CMC package to be included
18Key Considerations for Expedited Valrox Registration in the US 2019
Key Filing Elements for Accelerated Approval
Choice of Factor VIII Assay Chromogenic acceptable
FVIII in normal range Acceptable primary endpoint for
registration
ABR FVIII levels reasonably likely to
predict reduction
Longer-term data 3.5 years at time of filing
Comprehensive CMC Package Must use to-be-commercialized
materials in trials
19FVIII Activity Levels in Normal Range with Chromogenic Assay
Valrox Phase 1/2 data conforms to regulatory requirements for expedited registration
Valrox 6e13 vg/kg dose results to 52 weeks
Expedited Registration:
Powered based on Phase 1/2
The upper and lower box bounds represent 25th and 75th percentiles. The whisker lines represent the minimum and maximum values. 20Sustained Reduction of Annualized Bleed Rates Post Valrox Treatment
Valrox 104 week Phase 1/2 ABR data superior to Standard of Care
ABR results with 6e13 dose through week 104
97% REDUCTION in MEAN ABR
20
ABR (episodes/year)
16.5 16.3
15
10
5
0 0.9 0 0.5
0
Pre-infusion Post-infusion Post-infusion
(52 weeks) (104 weeks)
median mean
% Patients Bleed Free
Baseline Year 1 Year 2
14% 71% 86%
All patients off prophylaxis
100% resolution in target joints
As presented at WFH, May 22, 2018 21Global Hemophilia A Market in 2016 was $8.4B1
2
Fully-compliant, WAC pricing for FVIII replacement in adults is $403K-$674K per year
EUMEA total: ~64,000
NORAM total: ~18,000
Hemophilia A Severity
Source: WFH 2016
LATAM total: ~22,000 APAC: ~13,000
An Estimated 117K Hemophilia A Patients in our Territories 3
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 EPI Data from 2016 WFH Annual Survey; NHF website: http://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A; 22In-house Manufacturing Capabilities Support more Rapid Development Program
BioMarin’s FULLY INTEGRATED VECTOR PRODUCTION FACILITY
Biologics Facility Gene Therapy 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
Reduces Risk By Developing Commercial Ready Processes To Support Pivotal Clinical Studies
BMN 270 Phase 3 Studies Being Conducted With Material Made At Commercial Scale in the to be Commercial Facility
BMN 307 Clinical Studies Will Be Conducted With Material Made At Commercial Scale in the to be Commercial Facility 23What’s Next?
BioMarin’s Formula for “Medium Rare” Disease
Drug DevelopmentOur Enriched Approach for Speed and Success
4 Key Criteria Guide Discovery and Development at BioMarin
• IND to approval in 4-6
• High unmet need and rapid
1 development
years for 5 out of 7
products
Phe
• Hem A, PKU, CLN2,
• Diseases with genetic
2 x
PAH
Tyr
mechanisms
MPS I, IVA, VI,
achondroplasia
• Gene therapy to restore
• Target epicenters and drive for
33 normalization
FVIII expression in Hem A
and PAH activity in PKU
FVIII • Hem A, PKU, MPS:
• Discern outcomes through
4 Phe sensitive endpoints
Rapidly gauge efficacy with
relevant endpoints
25BMN 307: Leveraging Our Leading Gene Therapy Capabilities
Core gene therapy expertise Improved tissue tropism with novel
across 5 domains BMRN AAVs – muscle example
AAV9 AAV BMRN
1
Tissue
tropism
5 2
Pre-existing Novel BMRN AAVs with less
Expression susceptibility to pre-existing immunity
immunity
4 3
Vector
Manufacturing
optimization
Reference: Data on file, BioMarin (2018) 26BMN 307 and the PKU Model Used for Development
BMN 307: Liver-directed gene therapy (AAV5 PAH)
IND filing in 2H19 (Commercial scale material available in 2H19)
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
WT
ENU2
27Lifetime Phe Correction seen in Treated PKU Mice with BMN 307; IND 2H19
Phenylalanine reductions seen in ENU2 mice
Phe in µM
ENU2 vehicle
ENU2 + AAV5 muPAH
WT vehicle • AAV5-PAH
normalizes Phe in
ENU2 mice
• Levels
indistinguishable
from WT after 2
ENU2 + AAV5 PAH weeks
• Efficacy
sustained at 80
weeks
2 weeks
Reference: Data on file, BioMarin (2018) 282018 Final Financial Guidance Largely in-line with Prior Guidance
Reaffirmed Y/Y revenue growth of approximately 15% through 2020; $2B in 2020
Revenue Guidance ($ in millions)
Item 2018 Guidance Final 2018 Guidance
Total BioMarin Revenues $1,470 to $1,530 Unchanged
Vimizim Net Product Revenue $460 to $500 Unchanged
Naglazyme Net Product Revenue $325 to $355 Unchanged
Kuvan Net Product Revenue $440 to $480 $430 to $450
Brineura Net Product Revenue $35 to $55 Unchanged
Palynziq Net Product Revenue $10 to $14 Unchanged
Selected Income Statement Guidance
($ in millions, except percentages)
Item 2018 Guidance
Cost of Sales (% of Total Revenue) 20.0% to 21.0% 20.25% to 21.25%
SG&A Expense $575 to $615 Unchanged
R&D Expense $680 to $710 Unchanged
Non-GAAP Net Income $100 to $140 $90 to $105
GAAP Net Loss $(115) to $(165) $(100) to $(115)
All Financial Guidance items are calculated based on Generally Accepted Accounting Principles (GAAP) with the exception of Non-GAAP Income. Refer to Non-GAAP Information beginning on page 10 of this press release for a complete discussion of 29
the Company's Non-GAAP financial information and reconciliations to the comparable GAAP reported information.THANK YOU
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