UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
____________
Form 10-K
____________
(Mark One)
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
☐
Or
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2022
For the transition period from to .
Commission file number: 000-26727
____________
BioMarin Pharmaceutical Inc.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
770 Lindaro Street
San Rafael
California
(Address of principal executive offices)
68-0397820
(I.R.S. Employer
Identification No.)
94901
(Zip Code)
(415) 506-6700
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Common Stock, par value $.001
Trading Symbol(s)
BMRN
Name of each exchange on which registered
The Nasdaq Global Select Market
Securities registered under Section 12(g) of the Act:
None
____________
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☒ No ☐
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for
such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this
chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the
definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and "emerging growth company" in Rule 12b-2 of the Exchange Act.
Large accelerated filer
Non-accelerated filer
☒
☐
Accelerated filer
Smaller reporting company
Emerging Growth company
☐
☐
☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting
standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under
Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. Yes ☒ No ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act.) Yes ☐ No ☒
The aggregate market value of the voting and non-voting common stock held by non-affiliates of the registrant as of June 30, 2022 was $9.0 billion, based on the closing price reported for such date on
the Nasdaq Global Select Market.
As of February 16, 2023, the registrant had 186,528,784 shares of common stock, par value $0.001, outstanding.
Documents Incorporated by Reference: Specified portions of the registrant's definitive proxy statement for the registrant's 2023 annual meeting of stockholders, which will be filed with the Commission
no later than 120 days after the end of the registrant's fiscal year ended December 31, 2022, are incorporated by reference under Part III of this Annual Report on Form 10-K.
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Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6.
Item 7.
Item 7A.
Item 8.
Item 9.
Item 9A.
Item 9B.
Item 9C.
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
Item 15.
Item 16.
BIOMARIN PHARMACEUTICAL INC.
2022 FORM 10-K ANNUAL REPORT
TABLE OF CONTENTS
Part I
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Part II
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
[Reserved]
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosure About Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Directors, Executive Officers and Corporate Governance
Executive Compensation
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions and Director Independence
Principal Accounting Fees and Services
Part III
Exhibits, Financial Statement Schedules
Form 10-K Summary
SIGNATURES
Part IV
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Unless the context suggests otherwise, references in this Annual Report on Form 10-K to “BioMarin,” the “Company,” “we,” “us,” and “our” refer to
BioMarin Pharmaceutical Inc. and, where appropriate, its wholly owned subsidiaries.
BioMarin , BRINEURA , KUVAN , NAGLAZYME , PALYNZIQ , VIMIZIM and VOXZOGO are our registered trademarks. ROCTAVIAN™ is a
®
®
®
®
®
®
®
trademark of BioMarin Pharmaceutical Inc. ALDURAZYME is a registered trademark of BioMarin/Genzyme LLC. All other brand names and service marks,
trademarks and other trade names appearing in this report are the property of their respective owners.
®
Forward-Looking Statements
This Annual Report on Form 10-K contains “forward-looking statements” as defined under securities laws. Many of these statements can be
identified by the use of terminology such as “believes,” “expects,” “intends,” “anticipates,” “plans,” “may,” “will,” “could,” “would,” “projects,” “continues,”
“estimates,” “potential,” “opportunity” or the negative versions of these terms and other similar expressions. You should not place undue reliance on these
types of forward-looking statements, which speak only as of the date that they were made. These forward-looking statements are based on the beliefs and
assumptions of our management based on information currently available to management and should be considered in connection with any written or oral
forward-looking statements that we may issue in the future as well as other cautionary statements we have made and may make. Our actual results or
experience could differ significantly from the forward-looking statements. Factors that could cause or contribute to these differences include those discussed
in the section titled “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K as well as information provided elsewhere in this Annual Report on
Form 10-K. You should carefully consider that information before you make an investment decision. Moreover, we operate in a very competitive and rapidly
changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all
factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any
forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in
this Annual Report on Form 10-K may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-
looking statements.
Except as required by law, we do not undertake any obligation to release publicly any revisions to these forward-looking statements after
completion of the filing of this Annual Report on Form 10-K to reflect later events or circumstances or the occurrence of unanticipated events.
The following is a summary of the principal risks that could adversely affect our business, financial condition, operating results, cash flows or stock
price. Discussion of the risks listed below, and other risks that we face, are discussed in the section titled “Risk Factors” in Part I, Item 1A of this Annual
Report on Form 10-K.
Risk Factors Summary
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Business and Operational Risks
If we fail to obtain and maintain an adequate level of coverage and reimbursement for our products by third-party payers, the sales of our products
would be adversely affected or there may be no commercially viable markets for our products.
Because the target patient populations for our products are relatively small, we must achieve significant market share and maintain high per-patient
prices for our products to achieve and maintain profitability.
If we fail to compete successfully with respect to product sales, we may be unable to generate sufficient sales to recover our expenses related to
the development of a product program or to justify continued marketing of a product and our revenues could be adversely affected.
Changes in methods of treatment of disease could reduce demand for our products and adversely affect revenues.
If we fail to develop new products and product candidates or compete successfully with respect to acquisitions, joint ventures, licenses or other
collaboration opportunities, our ability to continue to expand our product pipeline and our growth and development would be impaired.
The sale of generic versions of KUVAN by generic manufacturers has adversely affected and will continue to adversely affect our revenues and
may cause a decline in KUVAN revenues faster than expected.
If we do not achieve our projected development goals in the timeframes we announce or fail to achieve such goals, the commercialization of our
product candidates may be delayed or never occur and the credibility of our management may be adversely affected and, as a result, our stock
price may decline.
Regulatory Risks
If we fail to obtain regulatory approval to commercially market and sell our product candidates, or if approval of our product candidates is delayed,
we will be unable to generate revenues from the sale of these product candidates, our potential for generating positive cash flow will be diminished,
and the capital necessary to fund our operations will increase.
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Any product for which we have obtained regulatory approval, or for which we obtain approval in the future, is subject to, or will be subject to,
extensive ongoing regulatory requirements by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other
comparable international regulatory authorities, and if we fail to comply with regulatory requirements or if we experience unanticipated problems
with our products, we may be subject to penalties, we will be unable to generate revenues from the sale of such products, our potential for
generating positive cash flow will be diminished, and the capital necessary to fund our operations will be increased.
To obtain regulatory approval to market our products, preclinical studies and costly and lengthy clinical trials are required and the results of the
studies and trials are highly uncertain. Likewise, preliminary, initial or interim data from clinical trials should be considered carefully and with caution
because the final data may be materially different from the preliminary, initial or interim data, particularly as more patient data become available.
Government price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our current and future
products, which would adversely affect our revenues and results of operations.
Government healthcare reform could increase our costs and adversely affect our revenues and results of operations.
Risks Related to Our Gene Therapy Programs
Our gene therapy products and product candidates are based on a novel technology, which presents additional development, manufacturing,
regulatory and treatment risks in relation to our other, more traditional drug development programs.
As compared to our other, more traditional products, gene therapy products may present additional problems with respect to the pricing, coverage,
and reimbursement and acceptance of the product.
Financial and Financing Risks
If we incur operating losses or are unable to sustain positive cash flows for a period longer than anticipated, we may be unable to continue our
operations at planned levels and may be forced to reduce our operations.
Manufacturing Risks
If we fail to comply with manufacturing regulations, our financial results and financial condition will be adversely affected.
If we are unable to successfully develop and maintain manufacturing processes for our product candidates to produce sufficient quantities at
acceptable costs, we may be unable to support a clinical trial or be forced to terminate a program, or if we are unable to produce sufficient
quantities of our products at acceptable costs, we may be unable to meet commercial demand, lose potential revenue, have reduced margins or be
forced to terminate a program.
Supply interruptions may disrupt our inventory levels and the availability of our products and product candidates and cause delays in obtaining
regulatory approval for our product candidates, or harm our business by reducing our revenues.
Risks Related to International Operations
• We conduct a significant amount of our sales and operations outside of the U.S., which subjects us to additional business risks that could adversely
affect our revenues and results of operations.
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A significant portion of our international sales are made based on special access programs, and changes to these programs could adversely affect
our product sales and revenues in these countries.
Our international operations pose currency risks, which may adversely affect our operating results and net income.
Intellectual Property Risks
If we are unable to protect our intellectual property, we may not be able to compete effectively or preserve our market shares.
Competitors and other third parties may have developed intellectual property that could limit our ability to market and commercialize our products
and product candidates, if approved.
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Table of Contents
Item 1. Business
Overview
Part I
Founded in 1997, BioMarin Pharmaceutical Inc. (BioMarin, we, us or our) is a global biotechnology company dedicated to transforming lives
through genetic discovery. We develop and commercialize targeted therapies that address the root cause of genetic conditions. Our robust research and
development capabilities have resulted in multiple innovative commercial therapies for patients with rare genetic disorders. Our distinctive approach to drug
discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-
understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options.
Recent Developments
In 2022, we achieved nearly $2.1 billion in total revenues, including a significant contribution from our ongoing launch of VOXZOGO, and we
continued making important advancements in our product development pipeline. Our key business developments since the beginning of 2022 include the
conditional approval of ROCTAVIAN (formerly referred to as valoctocogene roxaparvovec) in the European Union (EU) for the treatment of severe
hemophilia A in adult patients, our release of positive three-year data from our Phase 3 study of ROCTAVIAN, the acceptance by the U.S. Food and Drug
Administration (FDA) of our resubmission of the Biologics License Application (BLA) for ROCTAVIAN, and approvals of VOXZOGO in Australia for patients
with achondroplasia ages two and older and in Japan for children with achondroplasia of all ages. We also continued progress in our earlier stage clinical
programs, BMN 255 for the treatment of hyperoxaluria in chronic liver disease and BMN 331, a gene therapy product candidate for Hereditary Angioedema
(HAE). Please see the disclosures below in this Part I, Item 1 of this Annual Report on Form 10-K for further discussion of these recent developments.
Commercial Products
A summary of our commercial products is provided below:
Commercial Products
Products marketed by BioMarin:
VIMIZIM (elosulfase alpha)
NAGLAZYME (galsulfase)
PALYNZIQ (pegvaliase-pqpz)
KUVAN (sapropterin dihydrochloride)
VOXZOGO (vosoritide)
BRINEURA (cerliponase alfa)
ROCTAVIAN (valoctocogene roxaparvovec)
(2)
(5)
Products not marketed by BioMarin:
ALDURAZYME (laronidase)
(6)
(1) Mucopolysaccharidosis
(2) For the treatment of adult patients with phenylketonuria (PKU)
Indication
2022 Net Product
Revenues
(1)
MPS IVA
MPS VI
PKU
PKU
Achondroplasia
(4)
CLN2
Severe Hemophilia A
(3)
MPS I
$
$
$
$
$
$
$
$
663.8
443.8
255.0
227.6
169.1
154.3
—
128.4
(3) For the treatment of achondroplasia in children aged five years and older for the U.S., aged two years and older for the EU and for various age ranges
for other markets. For more information, see “VOXZOGO” below.
(4) Neuronal ceroid lipofuscinosis type 2
(5) The European Commission (EC) conditionally approved ROCTAVIAN in the third quarter of 2022, but no sales occurred in 2022. For more information,
see “ROCTAVIAN” below.
(6) Marketed by Sanofi
VIMIZIM
VIMIZIM is an enzyme replacement therapy for the treatment of MPS IVA, a lysosomal storage disorder. MPS IVA is a disease characterized by
deficient activity of N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage of certain complex carbohydrates known as
glycosaminoglycans (GAGs), such as keratan sulfate and chondroitin sulfate. This excessive storage causes a systemic skeletal dysplasia, short stature,
and joint abnormalities, which limit mobility and endurance.
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Malformation of the chest impairs respiratory function, and looseness of joints in the neck cause spinal instability and potentially spinal cord compression.
Other symptoms may include hearing loss, corneal clouding, and heart disease. Initial symptoms often become evident in the first five years of life. The
disease substantially limits both the quality and length of life of those affected.
VIMIZIM is approved for marketing in the U.S., the EU and other international markets.
NAGLAZYME
NAGLAZYME is a recombinant form of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) indicated for patients with MPS VI. MPS VI is a
debilitating life-threatening genetic disease for which no other drug treatment currently exists and is caused by the deficiency of arylsulfatase B, an enzyme
normally required for the breakdown of GAGs. Patients with MPS VI typically become progressively worse and experience multiple severe and debilitating
symptoms resulting from the build-up of carbohydrate residues in tissues in the body. These symptoms include: inhibited growth, spinal cord compression,
enlarged liver and spleen, joint deformities and reduced range of motion, skeletal deformities, impaired cardiovascular function, upper airway obstruction,
reduced pulmonary function, frequent ear and lung infections, impaired hearing and vision, sleep apnea, malaise and reduced endurance.
NAGLAZYME is approved for marketing in the U.S., the EU and other international markets.
PALYNZIQ
PALYNZIQ is a PEGylated recombinant phenylalanine (Phe) ammonia lyase enzyme, which is delivered through subcutaneous injection to reduce
blood Phe concentrations. PALYNZIQ is our second approved treatment for PKU. PALYNZIQ is approved for marketing in the U.S. for adult patients with
PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management. PALYNZIQ is also approved for marketing in
the EU and Australia for patients ages 16 and older who have inadequate blood Phe control (blood Phe concentrations greater than 600 micromol/L) despite
prior management with available treatment options.
In the U.S., PALYNZIQ is only available through the PALYNZIQ Risk Evaluation and Mitigation Strategy (REMS) program, which is required by the
FDA to mitigate the risk of anaphylaxis while using the product. Notable requirements of our REMS program include the following:
prescribers must be certified by enrolling in the REMS program and completing training;
prescribers must prescribe auto-injectable epinephrine with PALYNZIQ;
pharmacies must be certified with the REMS program and must dispense PALYNZIQ only to patients who are authorized to receive it;
patients must enroll in the REMS program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the
risks and benefits of treatment with PALYNZIQ; and
patients must have auto-injectable epinephrine available at all times while taking PALYNZIQ.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks posed by the REMS program.
•
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KUVAN
KUVAN is a proprietary synthetic oral form of 6R-BH4, a naturally occurring enzyme co-factor for phenylalanine hydroxylase (PAH), indicated for
patients with PKU. KUVAN is the first drug for the treatment of PKU, which is an inherited metabolic disease that affects at least 50,000 diagnosed patients
under the age of 40 in the developed world. We believe that approximately 30% to 50% of those with PKU could benefit from treatment with KUVAN. PKU is
caused by a deficiency of activity of an enzyme, PAH, which is required for the metabolism of Phe. Phe is an essential amino acid found in all protein-
containing foods. Without sufficient quantity or activity of PAH, Phe accumulates to abnormally high levels in the blood, resulting in a variety of serious
neurological complications, including severe mental retardation and brain damage, mental illness, seizures and other cognitive problems. As a result of
newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients under the age of 40 in developed countries have been
diagnosed at birth. Currently, PKU can be managed by a Phe-restricted diet, which is supplemented by nutritional replacement products, like formulas and
specially manufactured foods; however, it is difficult for most patients to adhere to the strict diet to the extent needed for achieving adequate control of blood
Phe levels.
KUVAN is approved for marketing in the U.S., the EU and other international markets (excluding Japan). In certain international markets, KUVAN is
also approved for, or is only approved for, the treatment of primary BH4 deficiency, a different disorder than PKU.
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Generic versions of KUVAN are available in several countries around the world, including multiple generic versions in the U.S. We are also aware
that manufacturers are challenging our patent portfolio related to KUVAN in several jurisdictions, and several generic versions of KUVAN have been
approved either centrally by the EMA or on a country-by-country basis throughout the EU. Please see “Risk Factors” included in Part I, Item 1A of this
Annual Report on Form 10-K for a discussion of the risks posed by generic versions of KUVAN in the U.S. and international markets.
VOXZOGO
VOXZOGO is a once daily injection analog of C-type Natriuretic Peptide (CNP) for the treatment of achondroplasia, the most common form of
disproportionate short stature in humans. In patients with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created,
is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 gene (FGFR3). VOXZOGO acts as a positive regulator of the
signaling pathway downstream of FGFR3 to promote endochondral bone growth.
VOXZOGO is approved for marketing in the EU, Australia and Brazil for patients with achondroplasia ages two and older with open growth plates
and in Japan for children with achondroplasia of all ages with open growth plates. The FDA granted accelerated approval for the use of VOXZOGO in the
U.S. for patients with achondroplasia ages five and older with open growth plates. The FDA issued us a Rare Pediatric Disease Priority Review Voucher
(PRV) in connection with VOXZOGO’s accelerated approval, which confers priority review to a subsequent drug application that would not otherwise qualify
for priority review. The PRV program is designed to encourage development of new drugs and biologics for the treatment of rare pediatric diseases. In the
first quarter of 2022, we sold the PRV we obtained in connection with VOXZOGO’s accelerated approval for a gross lump sum payment of $110.0 million.
We continue to research VOXZOGO’s safety and effectiveness in children with achondroplasia. On February 23, 2022, we announced results from
our Phase 2 randomized, double-blind, placebo-controlled clinical trial of VOXZOGO in infants and young children up to five years of age with
achondroplasia, and on June 13, 2022, we announced additional details from the analysis. Results at 52 weeks trended in favor of VOXZOGO compared to
placebo on height (adjusted for age and gender) and annualized growth velocity, consistent with improvements previously observed after one year of
treatment in children over five years of age and without significantly impacting upper-to-lower body segment ratio. The safety profile was generally consistent
with older children from the Phase 3 study and product label population. Serious adverse events (SAEs) were higher in the placebo group (18%) compared
to children treated with VOXZOGO (7%). All SAEs, including a fatal respiratory arrest (reported as a sudden infant death syndrome in a treated infant with
pre-existing respiratory morbidity), were deemed by the study investigators to be unrelated to treatment. The most common adverse events were mild and
self-limiting injection site reactions. As part of our efforts to expand access to VOXZOGO for younger children, on January 3, 2023, we announced that we
submitted, and the EMA subsequently validated, our Type II Variation application to extend the indication for VOXZOGO in the EU to treat children with
achondroplasia under the age of 2. We also announced that we submitted a supplemental New Drug Application (NDA) to the FDA to treat children with
achondroplasia under the age of 5. Additionally, on August 3, 2022, we announced our interventional Phase 2 study with VOXZOGO for the treatment of
infants under the age of two who are at risk for foramen magnum compression completed enrollment. The study is investigating the safety of VOXZOGO in
infants at risk of requiring surgery to alleviate compression at the foramen magnum, the opening in the base of the skull through which the spinal cord
passes.
Moreover, we are evaluating VOXZOGO as a potential treatment for children with other genetic short stature conditions beyond achondroplasia. A
52-week investigator-initiated study sponsored by Children's National Hospital in Washington, D.C. to investigate VOXZOGO in children with selected
genetic forms of short stature is ongoing and expected to complete in 2023. Preliminary 6-month results from 12 subjects demonstrated a positive response
in all subgroups with interindividual variability.
BRINEURA
BRINEURA is a recombinant human tripeptidyl peptidase 1 (TPP1) for the treatment of patients with CLN2, a form of Batten disease. CLN2 is an
incurable, rapidly progressive disease that typically ends in patient death by 10-12 years of age. Patients are initially healthy but begin to decline at
approximately the age of three. We estimate that up to 1,200 to 1,600 cases exist worldwide. BRINEURA is the first treatment approved to slow the
progression of loss of ambulation in children with CLN2 disease and was one of the first therapies to go through an accelerated review procedure in the EU.
BRINEURA is administered via intracerebroventricular (ICV) infusion and intended to be used in combination with a delivery device, such as an
injector or other delivery system. Please see “Government Regulation – Regulation of Product Marketing and Promotion – Combination Products” in this
Annual Report on Form 10-K for additional information on combination products.
BRINEURA is approved for marketing in the U.S. (for ages three and older) and in the EU (for all ages from birth) and in other international markets.
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ROCTAVIAN
ROCTAVIAN is an adeno associated virus (AAV5) vector gene therapy designed to restore factor VIII plasma concentrations in patients with severe
hemophilia A. Hemophilia A, also called factor VIII deficiency or classic hemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting
protein. According to the World Federation of Hemophilia rankings of severity of hemophilia A, the normal range of factor VIII activity levels is between 50%
and 150%, expressed as a percentage of normal factor activity in blood, the mild hemophilia A range of factor VIII activity levels is between 5% and 40%, the
moderate hemophilia A range of factor VIII activity levels is between 1% and 5%, and the severe hemophilia range of factor VIII activity levels is less than
1%. People living with hemophilia A are not able to form blood clots efficiently and are at risk for excessive bleeding from modest injuries, potentially
endangering their lives. People with severe hemophilia often bleed spontaneously into their muscles or joints.
Our European launch of ROCTAVIAN is underway following ROCTAVIAN'S conditional approval for marketing in the EU in August 2022 for the
treatment of severe hemophilia A in adult patients without a history of factor VIII inhibitors and without detectable antibodies to AAV5. We plan to provide the
EMA further clinical data to convert our conditional approval to a standard marketing authorization. Please see “Government Regulation – Adaptive
Pathways” in this Annual Report on Form 10-K for additional information on conditional marketing authorizations. Moreover, we completed outcomes-based
agreements (OBAs) for ROCTAVIAN with third-party payers in Germany, which make us subject to potential repayments if a patient does not respond to
therapy or the therapeutic effect of the drug falls below specified thresholds. We continue to collaborate with other payers to secure additional OBAs for
ROCTAVIAN, which are intended to assist payers with realizing the value and sharing the risk of a one-time treatment.
On October 12, 2022, we announced that the FDA accepted for review our resubmission of the BLA for ROCTAVIAN for the treatment of adults with
severe hemophilia A. The BLA resubmission incorporates our responses to all deficiencies identified in the FDA’s August 2020 Complete Response Letter to
our original BLA submission. The Prescription Drug User Fee Act (PDUFA) target action date for the resubmitted BLA is March 31, 2023. Typically, BLA
resubmissions are followed by a six-month review procedure. However, three additional months of review may be necessary in connection with our recent
submission to the FDA of data from our three-year analysis of the global Phase 3 study of ROCTAVIAN, as discussed below. Additionally, the FDA
completed a Pre-License Inspection of the ROCTAVIAN manufacturing facility in early December 2022. We have provided responses to the FDA’s comments
and observations received at the close of the inspection, and we believe all are addressable.
On May 31, 2022, we announced an update to our previously reported results of an open-label Phase 1/2 study of ROCTAVIAN for the treatment of
adults with severe hemophilia A. The six-year update for the 6e13 vg/kg and five-year update for the 4e13 vg/kg cohorts showed a sustained treatment
benefit of ROCTAVIAN. All participants, except one in the 4e13 vg/kg cohort as discussed below, had remained off prophylactic factor VIII treatment since
receiving their single dose of ROCTAVIAN. Six months prior to the data cut, one participant in the 4e13 vg/kg cohort temporarily resumed prophylactic factor
VIII treatment for one month, after which he was bleed free through the last follow up. In addition, the mean annualized bleed rates (ABR) for the most recent
year were less than one in both cohorts and below pre-treatment baseline levels.
On January 8, 2023, we announced topline results from our three-year analysis of the global Phase 3 study of ROCTAVIAN for the treatment of
adults with severe hemophilia A. All 132 study participants received a single dose of ROCTAVIAN and had a minimum of 36 months of follow-up. For a pre-
specified group of 112 participants (two of whom discontinued from the study prior to reaching three years of follow-up) in a non-interventional prospective
baseline observational study after dosing with ROCTAVIAN (the Rollover Population), in year three the mean ABR was reduced by 80% from baseline, with a
mean ABR for treated bleeds of 1.0 (median 0.0). For the Rollover Population, in year three the mean annualized factor VIII infusion rate was reduced by
94% from baseline, with a mean annualized infusion rate of 8.4 (median 0.0). As of the three-year data cut, 92% of the Rollover Population participants
remained off factor VIII prophylactic therapy. At the end of the three year post-infusion with ROCTAVIAN, the population of 132 participants had a mean
factor VIII activity level of 18.8 (median 8.4) IU/dL, as measured by the chromogenic substrate (CS) assay. In the 17 participants (one of whom discontinued
from the study prior to reaching four years of follow-up) who had been dosed at least four years prior to the data cut, mean factor VIII activity was 15.2
(median 7.4) IU/dL by the CS assay at the end of year three. The mean ABR for treated bleeds in year four for this subpopulation was 0.8 (median 0.0) and
the mean annualized infusion rate was 11.1 (median 0.0).
In addition to the ongoing Phase 1/2 and Phase 3 studies of ROCTAVIAN described above, we have multiple other clinical studies of ROCTAVIAN
underway. We are conducting an ongoing Phase 3, single arm, open-label study to evaluate the efficacy and safety of ROCTAVIAN at a dose of 6e13 vg/kg
with prophylactic corticosteroids in people with severe hemophilia A. We are also conducting an ongoing Phase 1/2 Study with the 6e13 vg/kg dose of
ROCTAVIAN in people with severe hemophilia A with pre-existing AAV5 antibodies and a Phase 1/2 Study with the 6e13 vg/kg dose of ROCTAVIAN in
people with severe hemophilia A with active or prior factor VIII inhibitors.
Overall, ROCTAVIAN continues to have a favorable safety profile and has been generally well tolerated by participants across all doses in the
Phase 1/2 and Phase 3 studies. No participants developed inhibitors to factor VIII, malignancy, or thromboembolic events. The most common adverse
events associated with ROCTAVIAN across studies occurred early and included transient infusion-associated reactions and mild to moderate rise in liver
enzymes with no long-lasting clinical sequelae.
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During year three of the Phase 3 study, no new treatment-related SAEs or Grade 3 events attributed to ROCTAVIAN or corticosteroid use emerged.
ALDURAZYME
ALDURAZYME is a highly purified protein that is designed to be identical to a naturally occurring form of the human enzyme alpha-L-iduronidase, a
lysosomal enzyme normally required for the breakdown of GAGs. MPS I is a progressive and debilitating life-threatening genetic disease, for which no other
drug treatment currently exists, that is caused by the deficiency of alpha-L-iduronidase. Patients with MPS I typically become progressively worse and
experience multiple severe and debilitating symptoms resulting from the build-up of carbohydrate residues in all tissues in the body. These symptoms
include: inhibited growth, delayed and regressed mental development (in the severe form of the disease), enlarged liver and spleen, joint deformities and
reduced range of motion, impaired cardiovascular function, upper airway obstruction, reduced pulmonary function, frequent ear and lung infections, impaired
hearing and vision, sleep apnea, malaise and reduced endurance.
We developed ALDURAZYME through collaboration with Sanofi. Under our collaboration agreement with Sanofi, we are responsible for
manufacturing ALDURAZYME and supplying it to Sanofi. We receive payments ranging from 39.5% to 50% on worldwide net ALDURAZYME sales by
Sanofi depending on sales volume. Sanofi and BioMarin are members of BioMarin/Genzyme LLC, a 50/50 limited liability company (the BioMarin/Genzyme
LLC) that: (1) holds the intellectual property relating to ALDURAZYME and other collaboration products and licenses all such intellectual property on a
royalty-free basis to Sanofi and BioMarin to allow us to exercise our rights and perform our obligations under the agreements related to the
BioMarin/Genzyme LLC, and (2) engages in research and development activities that are mutually selected and funded by Sanofi and us.
ALDURAZYME is approved for marketing in the U.S., the EU and other international markets.
Clinical Development Programs
A summary of our clinical development programs is provided below:
Clinical Development Programs
ROCTAVIAN
BMN 255
BMN 331
BMN 255
Target
Indication
Severe Hemophilia A
Hyperoxaluria
Hereditary Angioedema (HAE)
Stage
FDA regulatory review
Clinical Phase 1/2
Clinical Phase 1/2
BMN 255 is a small-molecule therapy that is designed to treat hyperoxaluria in chronic liver disease. We concluded the multiple-ascending dose
phase of the first-in-human study with BMN 255. In January 2023, we shared early data that demonstrated a rapid and potent increase in plasma glycolate
following treatment with BMN 255, which is predicted to have a profound reduction in oxalate excretion in patients. We plan to initiate and fully enroll an
expanded study in patients with chronic liver disease and hyperoxaluria in 2023. We believe the availability of a potent, orally bioavailable, small molecule
like BMN 255 may be able to significantly reduce disease and treatment burden in a patient population with significant unmet need.
BMN 331
BMN 331 is a gene therapy product candidate for HAE. Dosing continues in the Phase 1/2 HAERMONY study to evaluate BMN 331, an
investigational AAV5-mediated gene therapy for people living with HAE, including dose escalation to the 6e13vg/kg dose, which our non-clinical studies
project to provide therapeutic levels of C1-Inhibitor. In January 2023, we shared that the first participant treated with the 6e13vg/kg dose of BMN 331
demonstrated C1-Inhibitor levels that were approaching the normal range. A second participant is scheduled for dosing at the 6e13vg/kg dose level in the
near term.
Manufacturing
We manufacture the active pharmaceutical ingredients (API) for ALDURAZYME, NAGLAZYME, PALYNZIQ and VOXZOGO in our production
facilities located in Novato, California. We manufacture the API for BRINEURA and VIMIZIM in our manufacturing facility in Shanbally, Cork, Ireland. These
facilities have been inspected and have demonstrated compliance with current Good Manufacturing Practices (cGMPs) to the satisfaction of the FDA, the EC
and health agencies in other countries.
We contract with third parties to manufacture KUVAN API. All our product manufacturing (which includes vials, syringes, tablets, and powder) and
most packaging operations are performed by contract manufacturers. We expect to continue to contract with outside service providers for certain
manufacturing services, including drug substance, drug product, and packaging operations for our products. All of our facilities and those of any third-party
manufacturers will be subject to periodic inspections
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confirming compliance with applicable law and must pass inspection before we can manufacture our drugs for commercial sales. Third-party manufacturers’
facilities are subject to periodic inspections to confirm compliance with applicable law and must be cGMP certified. We believe that our current agreements
with third-party manufacturers and suppliers provide for ample operating capacity to support the anticipated clinical and commercial demand for these
products. In certain instances, there is only one approved contract manufacturer for certain aspects of the manufacturing process. In such cases, we attempt
to prevent disruption of supplies through supply agreements, maintaining safety stock and other appropriate strategies.
In July 2017, we commissioned our commercial-scale gene therapy manufacturing facility, located in Novato, California, where we conduct cGMP
production of ROCTAVIAN to support commercial sales in Europe, anticipated commercial demand in other markets and clinical development activities. The
facility has been inspected and has demonstrated compliance with cGMPs to the satisfaction of the EC. This facility also supports cGMP production of BMN
331 to support clinical development activities. This facility has the potential to produce multiple gene therapy products to meet global commercial demand,
depending on dose and production mix. The facility holds a GMP certificate and its production processes have been developed in accordance with
International Conference on Harmonisation Technical Requirements for Registration of Pharmaceuticals for Human Use facilitating worldwide registration
with health authorities.
Raw Materials
Raw materials and supplies required for the production of our products and product candidates are available in some instances from one supplier
and in other instances from multiple suppliers. In those cases where raw materials are only available through one supplier, such supplier may be either a
sole source (the only recognized supply source available to us) or a single source (the only approved supply source for us among other sources). We have
adopted policies to attempt, to the extent feasible, to minimize our raw material supply risks, including maintenance of greater levels of raw materials
inventory and implementation of multiple raw materials sourcing strategies, especially for critical raw materials. Although to date we have not experienced
any significant delays in obtaining any raw materials from our suppliers, we cannot provide assurance that we will not face shortages from one or more of
them in the future.
Sales and Marketing
We have established a commercial organization, including a sales force, to support our product lines directly in the U.S., Europe, South America
and certain other significant markets. For other selected markets, we have signed agreements with other companies to act as distributors of all our products,
other than ALDURAZYME. Most of these agreements generally grant the distributor the right to market the product in the territory and the obligation to
secure all necessary regulatory approvals for commercial or named patient sales. Additional markets are being assessed at this time and additional
agreements may be signed in the future.
Sanofi has the exclusive right to distribute, market and sell ALDURAZYME globally and is required to purchase its requirements exclusively from
us.
In the U.S., our products (other than ALDURAZYME) are marketed through our commercial teams, including sales representatives and supporting
staff members, who promote our products directly to physicians in specialties appropriate for each product. Outside of the U.S., our sales representatives
and supporting staff members market our products (other than ALDURAZYME). We believe that with moderate changes in 2023, the size of our sales force
will be appropriate to effectively reach our target customers in markets where our products are directly marketed. The launch of any future products, if
approved, will likely require expansion of our commercial organization, including our sales force, in the U.S. and international markets.
We utilize third-party logistics companies to store and distribute our products. Moreover, we use third-party vendors, such as advertising agencies,
market research firms and suppliers of marketing and other sales support-related services, to assist with our commercial activities.
Customers
Customers for our products (other than ALDURAZYME) include a limited number of specialty pharmacies and end-users, such as hospitals and
non-U.S. government agencies. We also sell our products (other than ALDURAZYME) to our authorized distributors and to certain larger pharmaceutical
wholesalers globally, which act as intermediaries between us and end-users and generally do not stock significant quantities of our products. However, in
certain countries, governments place large periodic orders for NAGLAZYME and VIMIZIM. The timing of these orders can be inconsistent and can create
significant quarter to quarter variation in our revenue. PALYNZIQ is currently distributed in the U.S. pursuant to the REMS program through a limited number
of
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certified specialty pharmacies. During 2022, 37% of our net product revenue was generated by three customers. Sanofi is our sole customer for
ALDURAZYME and is responsible for marketing and selling ALDURAZYME to third parties.
Competition
The biopharmaceutical industry is rapidly evolving and highly competitive. Within the industry, there are many public and private companies,
including pharmaceutical companies and biotechnology companies that have or may soon initiate programs for the same indications that our products and
product candidates are intended to treat. Furthermore, universities and non-profit research organizations may have research programs, both early-stage and
clinical, in the same disease areas. Our larger competitors may have advantages over us due to greater financial or scientific resources, lower labor and
other costs, or higher headcount and more robust organizational structures, while smaller competitors may have advantages over us due to lower overhead
costs, being more nimble, or being able to focus on a narrower set of indications or development programs. Our competitors have considerable experience
in drug manufacturing, preclinical and clinical research and development, regulatory affairs, marketing, sales, and distribution. They pursue broad patent
portfolios and other intellectual property to protect the products they are developing. Their products may outcompete ours due to one or more factors,
including faster progress through preclinical and clinical development, lower manufacturing costs, superior safety and efficacy, lower pricing, stronger patent
protection, and better marketing, sales, and distribution capabilities. In this event, our products and product candidates, if approved, could fail to gain
significant market share, and as a result, our business, financial condition and results of operations could be adversely affected.
Other than ROCTAVIAN and KUVAN, as described below, our products have no direct approved competition currently on the market in the U.S. or
the EU; however, other companies are in the development phase with new and generic products. Our products and product candidates have potential
competition from products under development either using similar technology to our programs or different treatment strategies. The following is a summary
of some of the primary possible future competitors for our products and product candidates, but the information below may not include all potential
competition.
Commercial Products
ALDURAZYME, NAGLAZYME, and VIMIZIM
In the mucopolysaccharidosis field, several companies are researching treatments using small molecules, gene therapy, and other novel
technologies. ALDURAZYME, for the treatment of MPS I, has potential competition from clinical stage product candidates from ArmaGen, Inc., JCR
Pharmaceuticals Co., Ltd (acquired by ArmaGen, Inc.)., Orchard Therapeutics Plc and RegenxBio Inc. and earlier stage product candidates, including
product candidates from Denali Therapeutics Inc. and Immusoft Corporation. NAGLAZYME, for the treatment of MPS VI, has potential competition from
clinical stage product candidates from Inventiva S.A. and Paradigm Biopharmaceuticals Limited and other potential candidates in earlier stages. VIMIZIM, for
the treatment of MPS IVA, has potential competition from preclinical product candidates from Esteve Pharmaceuticals, S.A., and RegenxBio Inc. and other
potential candidates in earlier stages.
BRINEURA
BRINEURA, for the treatment of CLN2, has potential competition from preclinical product candidates from Lexeo Therapeutics, Inc., RegenxBio Inc.
and the Roche Group.
KUVAN and PALYNZIQ
There are currently no other approved, non-generic drugs on the market in the U.S. or the EU for the treatment of PKU. However, generic versions
of KUVAN are available in several countries around the world, including multiple generic versions in the U.S. We are also aware that manufacturers are
challenging our patent portfolio related to KUVAN in several jurisdictions, and several generic versions of KUVAN have been approved either centrally by the
EMA or on a country-by-country basis throughout the EU. Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a
discussion of the risks posed by generic versions of KUVAN in the U.S. and international markets. KUVAN and PALYNZIQ also have potential competition
from clinical stage product candidates from Homology Medicines, Inc., Jnana Therapeutics Inc., Nestle Health Science, S.A., PTC Therapeutics, Inc. and
Synlogic, Inc. and earlier stage product candidates, including product candidates from Codexis, Inc, Generation Bio Co., LogicBio Therapeutics, Inc.,
Moderna Therapeutics, Inc., Sangamo Therapeutics, Inc. and SOM Innovation Biotech, S.A. We and other companies are also developing gene therapy
product candidates for PKU.
VOXZOGO
VOXZOGO, for the treatment of achondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S,
Pfizer, Inc., QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), Ribomic Inc. and Sanofi and preclinical product candidates from other
companies, including Astellas Pharma Inc.
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ROCTAVIAN
ROCTAVIAN, a gene therapy product candidate for severe hemophilia A, has potential competition from marketed recombinant factor VIII
replacement therapies, a novel bispecific antibody marketed by the Roche Group, and clinical stage programs, including gene therapy product candidates
under development by ASC Therapeutics, Inc., Bayer AG, Pfizer, Inc., the Roche Group and Sangamo Therapeutics, Inc. In addition, Novo Nordisk A/S,
Pfizer, Inc., the Roche Group and Sanofi are developing novel non-factor replacement product candidates in the clinic for the treatment of hemophilia A.
Clinical Development Programs
BMN 255
BMN 255, a small-molecule product candidate for hyperoxaluria in chronic liver disease, has potential competition from marketed products from
Alnylam Pharmaceuticals, Inc., clinical stage product candidates from BridgeBio Pharma, Inc., Chinook Therapeutics, Inc. and Dicerna Pharmaceuticals, Inc.
(a subsidiary of Novo Nordisk A/S.) and preclinical product candidates from other companies, including Amarna Therapeutics and Intellia Therapeutics, Inc.
BMN 331
BMN 331, a gene therapy product candidate for HAE, has potential competition from marketed products from BioCryst Pharmaceuticals, Inc., CSL
Behring GmbH and Takeda Pharmaceutical Company Limited, clinical stage product candidates from Astria Therapeutics, Inc., CSL Behring GmbH, Intellia
Therapeutics, Inc., Ionis Pharmaceuticals, Inc. and Pharvaris N.V. and preclinical product candidates from other companies, including Orchard Therapeutics,
Inc. and Spark Therapeutics, Inc. (a subsidiary of the Roche Group).
Patents, Proprietary Rights and Regulatory Exclusivity
Our success depends on an intellectual property portfolio that supports our future revenue streams and also erects barriers to our competitors. We
are maintaining and building our patent portfolio through: filing new patent applications; prosecuting existing applications; and licensing and acquiring new
patents and patent applications. Furthermore we seek to protect our ownership of know-how, trade secrets and trademarks through an active program of
legal mechanisms including registrations, assignments, confidentiality agreements, material transfer agreements, research collaborations and licenses.
U.S. patents, as well as most foreign patents, are generally effective for 20 years from the date the earliest application was filed. U.S. patents that
were issued on applications filed before June 8, 1995, may be effective until 17 years from the issue date, if that is later than the 20-year date. In some
cases, the patent term may be extended to recapture a portion of the term lost during regulatory review of the claimed therapeutic or, in the case of the U.S.,
because of U.S. Patent and Trademark Office (USPTO) delays in prosecuting the application. In the U.S., under the Drug Price Competition and Patent Term
Restoration Act of 1984 (commonly known as the Hatch-Waxman Act), a patent that covers a drug approved by the FDA may be eligible for patent term
extension (for up to five years, but not beyond a total of 14 years from the date of product approval) as compensation for patent term lost during the FDA
regulatory review process. The duration and extension of the term of foreign patents varies in accordance with local law. In the EU, Supplementary
Protection Certificates, or SPCs, are available to extend a patent term up to five years to compensate for patent protection lost during regulatory review.
Although all EU Member States must provide SPCs, SPCs must be applied for and granted on a country-by-country basis. Limited exceptions apply to the
protection conferred by the SPC.
The table below lists our outstanding patents and patent applications of primary importance for our products other than ALDURAZYME by territory,
general subject matter (including composition, methods of treatment and approved use, methods of production and purification, pharmaceutical compositions
and clinical formulations) and latest expiry date. With respect to ALDURAZYME, the last of our patents expired in November 2020. One or more patents with
the same or earlier expiry dates may fall under the same general subject matter and are not listed separately in the table below. We continue to pursue
additional patents and patent term extensions in the U.S. and other territories covering various aspects of our products that may, if issued, extend patent
exclusivity beyond the expiration dates listed in the table below.
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Product
Territory
Patent No(s).
General Subject Matter
Patent Expiration
BRINEURA
U.S.
KUVAN
NAGLAZYME
PALYNZIQ
EU
EU
U.S.
EU
U.S.
EU
8,029,781
9,044,473
10,279,015
1673104
Method of treatment
Method of treatment by administration into the
cerebrospinal fluid
Formulation; kit
Pharmaceutical composition
16793229.2
(2)
Formulation
March 7, 2023
(1)
February 18, 2032
May 5, 2036
August 30, 2024
May 5, 2036
3138566; 3977999
(2)
Use for treating with once daily dosing regimen
November 17, 2024
2545939;
3461503; 4029519
(2)
Use for treating once daily after a meal
Use for treating after a meal
7,713,709
Antibody assays
1565209; 2327414
Compositions; pharmaceutical compositions; use to treat
an enzyme deficiency
7,534,595
Composition; method of treating
10,221,408
9,557,340
11,505,790
2152868
Purification
Antibody detection assay
Regimen
Composition; pharmaceutical composition
2531209; 3025728
Formulation; purification
April 11, 2028
April 11, 2028
July 20, 2028
November 7, 2023
August 16, 2027 / May
24, 2032
(3)
February 3, 2031
July 30, 2029
February 3, 2031
May 23, 2028 / May
(4)
23, 2033
February 03, 2031
ROCTAVIAN
US
9,504,762; 10,463,718;
11,406,690
Compositions, Methods of Treatment, Production
September 10, 2034
(5)
VIMIZIM
EU
U.S.
EU
VOXZOGO
U.S.
EU
10,512,675
Formulation, Clinical Methods of Treatment
September 23, 2036
3044231
Compositions, Methods of Treatment
September 30, 2034
(6)
8,128,925
8,765,437
2245145
2595650
8,198,242
9,907,834
10,646,550
2432489
Compositions; methods of treatment
Purification; formulation; methods of treatment
Composition; use for treating
April 10, 2030
January 10, 2032
April 30, 2029
(7)
Purification; composition; use for treating; formulation
July 22, 2031
Compositions, Methods of Treatment
Formulation
Clinical methods of treatment
Compositions, Methods of Treatment
June 11, 2030
(8)
August 1, 2036
August 1, 2036
May 20, 2030
(9)
(1) Under a patent term extension (PTE) that has been granted
(2) Patent application
(3) We filed for a PTE for this patent, and if granted, the patent expiration will extend to May 24, 2032.
(4) We applied for SPCs for this patent, and we have to date received SPC to extend the patent expiration to May 23, 2033 in certain European countries,
including Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland France, Greece, Hungary, Ireland, Iceland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Portugal, Spain, Slovenia and Sweden.
(5) We filed for a PTE for these patents, and if granted, the patents’ expirations will extend to September 10, 2039.
(6) We applied for SPCs for this patent, and we have to date received SPC to extend the patent expiration to September 10, 2037 in certain European
countries, including Austria, Belgium, Bulgaria, Cyprus, Germany, Denmark, Estonia, Spain, Finland, France, United Kingdom, Croatia, Hungary,
Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sweden and Slovakia.
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(7) We applied for SPCs for this patent, and we have to date received SPC to extend the patent expiration to April 30, 2029 in certain European countries,
including Austria, Bulgaria, Cypress, Czech Republic, Denmark, Estonia, Finland, France, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Netherlands, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland and the United Kingdom.
(8) We filed for a PTE for this patent, and if granted, the patent expiration will extend to May 20, 2035.
(9) We applied for SPCs for this patent in Hungary, Germany, Poland, Netherlands, Norway, Denmark, Czech Republic, Italy, France, Spain, Greece,
Belgium, Finland, Sweden, Ireland, Croatia, Austria and the United Kingdom, and have been granted SPCs so far in Italy and Austria extending the
patent expiration to May 30, 2035.
In addition to patent protection, certain of our products are entitled to regulatory exclusivity in the U.S. and the EU through the dates set forth below:
Commercial Products
BRINEURA
PALYNZIQ
ROCTAVIAN
VIMIZIM
VOXZOGO
United States
Orphan
Drug
Exclusivity
(1)
Expiration
2024
2025
Pending
Expired
2028
United
States
Biologic
Exclusivity
(2)
Expiration
2029
2030
Pending
2026
Not Applicable
European
Union
Orphan Drug
Exclusivity
(1)
Expiration
2027
2029
2032
2024
2031
(1) See “Government Regulation—Other Regulation—Orphan Drug Designation” in this Annual Report on Form 10-K for further discussion.
(2) See “Government Regulation—Other Regulation—Exclusivity for Biologics in the U.S.” in this Annual Report on Form 10-K for further discussion.
With respect to our clinical product candidates, we believe we have the necessary intellectual property rights to allow us to undertake the
development of these candidates. Certain of our product candidates are in therapeutic areas that have been the subject of many years of extensive research
and development by academic organizations and third parties who may control patents or other intellectual property that they might assert against us, should
one or more of our product candidates in these therapeutic areas succeed in obtaining regulatory approval and thereafter be commercialized. We continually
evaluate the intellectual property rights of others in these areas in order to determine whether a claim of infringement may be made by others against us.
Should we determine that a third party has intellectual property rights that could impact our ability to freely market a compound we consider a number of
factors in determining how best to prepare for the commercialization of any such product candidate. In making this determination we consider, among other
things, the stage of development of our product candidate and whether we and our outside counsel believe the intellectual property rights of others are valid,
whether we infringe the intellectual property rights of others, whether a license is available upon commercially reasonable terms, whether we will seek to
challenge the intellectual property rights of others, and the likelihood of and liability resulting from an adverse outcome should we be found to infringe the
intellectual property rights of others.
Government Regulation
Regulation by governmental authorities in the U.S., European countries and other countries is a significant factor in the development, manufacture,
commercialization, pricing and reimbursement of our products. Our industry is subject to significant federal, state, local and non-U.S. regulation. Our
products require approval from the FDA, the EC (on the basis of the scientific opinions issued by the EMA) and corresponding agencies in other countries
before they can be marketed. Failure to comply with applicable U.S. and foreign requirements may subject a company to a variety of administrative or
judicial sanctions, such as FDA refusal to approve pending NDAs or BLAs, warning or untitled letters, product recalls, product seizures, total or partial
suspension or withdrawal of marketing, production or distribution authorizations, injunctions, fines, civil penalties, and criminal prosecution.
Approval Process in the U.S. and EU
Satisfaction of FDA and EU pre-market approval requirements typically takes many years and the actual time required may vary substantially based
upon the type, complexity and novelty of the product or disease. Pharmaceutical product development in the U.S. and the EU typically involves preclinical
laboratory and animal tests, the submission to the applicable regulatory agency of an application (e.g., an IND in the U.S. or a CTA in the EU), which must
become effective before clinical testing may commence, and adequate and well-controlled human clinical trials to establish the safety and effectiveness of
the drug for each indication for which marketing approval is sought. On January 31, 2022, Regulation EU No 536/2014 (CTR) became fully applicable in the
EU. The CTR established a centralized application procedure where one of the National Competent Authorities
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(NCA) of the Member States where the trial will take place takes the lead in reviewing certain aspects of the application, while the other NCAs have a lesser
involvement than they had under the previous regime established by Directive 2001/20/EC (CTD). The CTD indeed introduced the first set of harmonized
rules on clinical trials in the EU but resulted in a patchwork of different national regimes. The CTR was adopted with a view to introducing a more uniform set
of the rules across the EU for the authorization of clinical trials. Such authorization still involves the national regulatory authorities and Ethics Committees of
each of the EU Member States where the trial is to be conducted. However, the relevant procedures have now been streamlined with a view to facilitating a
swifter and more seamless authorization and deployment of multi-center trials occurring in more than one EU Member State. More specifically, the CTR
allows sponsors to rely on one single submission for CTAs regardless of the number of Member States where the trial takes place and based on a single
harmonized application. Furthermore, under the CTR, deadlines for regulatory approvals are shortened with a view to accelerating the authorization process.
The CTR also established an EU Portal which will act as a single-entry point for submission of data and information relating to clinical trials. Until January 30,
2025, the CTD will continue to apply in parallel to the CTR for a transitional period. From January 31, 2025 all trials will have to comply with the CTR.
Preclinical tests include laboratory evaluation, as well as animal studies, to assess the characteristics and potential pharmacology,
pharmacokinetics and toxicity of the product. The conduct of the preclinical tests must comply with FDA and/or EU and national regulations and
requirements, including good laboratory practices (GLP). The results of preclinical testing, along with other information, including information about product
chemistry, manufacturing and controls and a proposed clinical trial protocol are reviewed by the applicable regulatory agency as part of an IND or CTA.
Long-term preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND or CTA is submitted. Until the CTA or
IND is approved, or becomes effective following a waiting period, and appropriate reviews have been satisfactorily completed by the applicable Institutional
Review Boards (IRBs) or Ethics Committees, we may not start the clinical trial in the relevant jurisdiction.
Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified
investigator. Clinical trials must be conducted in compliance with applicable regulations, good clinical practices (GCP), as well as under protocols detailing
the objectives of the trial and the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol involving testing on
patients and subsequent protocol amendments must be submitted to the FDA as part of the IND and to the relevant regulatory agency in the EU as part of a
new CTA.
The regulatory agencies may order the temporary halt or permanent discontinuation of a clinical trial at any time or impose other sanctions if they
believe that the clinical trial is not being conducted in accordance with applicable requirements or presents an unacceptable risk to the clinical trial patients.
An IRB/Ethics Committee may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB/Ethics
Committee’s requirements, or may impose other conditions. Clinical trials that are deployed to support NDAs, BLAs or Marketing Authorization Applications
(MAAs) for marketing approval are typically conducted in three sequential phases, but the phases may overlap or be combined. Typically, we undertake a
three-phase human clinical testing program as follows:
•
•
•
Phase 1 - the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics,
pharmacological actions, side effects associated with increasing doses and, if possible, early evidence on effectiveness.
Phase 2 - usually involves trials in a limited patient population, to determine the effectiveness of the drug for a particular indication or indications,
dosage tolerance and optimum dosage, and to identify common adverse effects and safety risks. If a compound demonstrates evidence of
effectiveness and an acceptable safety profile in Phase 2 evaluations.
Phase 3 - undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically
dispersed clinical trial sites.
After completion of the required clinical testing, an application is prepared and submitted to the applicable regulatory agency. Approval of the
application by the applicable regulatory agency is required before marketing of the product may begin. In the European Economic Area (i.e., the EU as well
as Iceland, Liechtenstein and Norway) (the EEA), there are two types of marketing authorizations (MA), namely: (i) the “Union” MA, which is issued by the
EC through the so-called “centralized procedure”, based on the positive opinion of the EMA’s Committee for Medicinal Products for Human Use (CHMP), and
results in a single marketing authorization that is valid across the EEA; and (ii) “National MAs,” which are issued by the competent NCAs and only cover their
respective territory. The centralized procedure is mandatory for certain types of products such as: (i) medicinal products derived from certain biotechnology
processes, (ii) designated orphan medicinal products, (iii) medicinal products containing a new active substance indicated for the treatment of certain
diseases such as HIV/AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases and other auto-immune dysfunctions, viral diseases; and
(iv) Advanced Therapy Medicinal Products (ATMPs) (such as gene therapy, somatic cell therapy or tissue-engineered medicines). The NDA, BLA or MAA
must include the results of all preclinical, clinical and other testing, a compilation of data relating to the product’s pharmacology, chemistry, manufacture and
controls and proposed labeling, among other things. In the U.S., each NDA or BLA is subject to a significant user fee at the time of submission, unless a
waiver is granted by the FDA. Similarly, in the EU, the submission of an MAA is subject to the payment of fees, a waiver of which may be obtained only
under limited circumstances. The FDA and the EMA initially review the applications for a threshold determination that it is sufficiently complete to permit
substantive review. The regulatory agency
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may request additional information rather than accepting an application for filing or validation. Once the submission is accepted, the applicable agency
begins an in-depth review. For the FDA, the review period for standard review applications is typically an additional ten months and, for priority review of
drugs, that is, drugs that the FDA determines address a significant unmet need and represent a significant improvement over existing therapy, the review
period is typically an additional six months in duration. The review process may be extended by the FDA for three additional months to consider new
information submitted during the review or clarification regarding information already provided in the submission. The FDA may also refer applications for
novel products or products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other
experts, for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an
advisory committee, but it generally follows such recommendations. After the FDA evaluates the information provided in the NDA/BLA, it issues an approval
letter, or a complete response letter. A complete response letter outlines the deficiencies in the submission and may require substantial additional testing or
information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed and the NDA/BLA has been resubmitted,
the FDA will re-initiate review. If it is satisfied that the deficiencies have been addressed, the FDA will issue an approval letter.
Under the centralized procedure in the EU, the maximum timeframe for the evaluation of an MAA by the EMA is 210 days. This excludes so-called
clock stops, during which additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP. At the end of
the review period, the CHMP provides an opinion to the EC. If the opinion is favorable, the EC may then adopt a decision to grant marketing authorization. In
the event of a negative opinion, the company may request a re-examination of the application within 15 days of receipt of the negative opinion. The company
then has 60 days to provide the CHMP with detailed grounds for requesting the re-examination. Within 60 days of providing this information, the CHMP must
re-examine its opinion. The EC follows the recommendation of the CHMP in almost all cases. In exceptional cases, the CHMP might perform an accelerated
review of an MAA in no more than 150 days. This is usually when the product is of major interest from the point of view of public health and, in particular,
from the viewpoint of therapeutic innovation.
During the review period, the FDA and/or the European authorities may typically inspect one or more clinical sites and/or the sponsor to assure
compliance with GCP regulations and may equally inspect the facility or the facilities at which the drug is manufactured to ensure compliance with cGMPs
regulations. Neither the FDA nor the EC will approve the product unless compliance is satisfactory and the application contains data that provide substantial
evidence that the drug is safe and effective in the indication studied.
Fast Track Designation and Accelerated Approval
The FDA is required to facilitate the development and expedite the review of drugs that are intended for the treatment of a serious or life-threatening
condition for which there is no effective treatment and that demonstrate the potential to address unmet medical needs for the condition. Under the FDA’s fast
track program, the sponsor of a new drug candidate may request that the FDA designate the drug candidate for a specific indication as a fast track drug
concurrent with or after the filing of the IND for the drug candidate. The FDA must determine if the drug candidate qualifies for fast track designation within
60 days of receipt of the sponsor’s request.
In addition to other benefits, such as the ability to use surrogate endpoints and have greater interactions with the FDA, the FDA may initiate review
of sections of a fast track drug’s NDA or BLA before the application is complete. This rolling review is available if the applicant provides and the FDA
approves a schedule for the submission of the remaining information and the applicant pays applicable user fees. However, the FDA’s time period goal for
reviewing an application does not begin until the last section of the NDA or BLA is submitted. Additionally, the fast track designation may be withdrawn by the
FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.
Under the fast track program and the FDA’s accelerated approval regulations, the FDA may approve a drug for a serious or life-threatening illness
that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical
benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on
irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of
alternative treatments. In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a
direct measurement of how a patient feels, functions, or survives. Surrogate endpoints can often be measured more easily or more rapidly than clinical
endpoints. A drug candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of a Phase 4 or
post-approval clinical trial to confirm the effect on the clinical endpoint. Failure to conduct a required post-approval study or confirm a clinical benefit through
a post-marketing study will allow the FDA to withdraw the drug from the market on an expedited basis. All promotional materials for drug candidates
approved under accelerated regulations are subject to prior review by the FDA. The Food and Drug Omnibus Reform Act (FDORA) was recently enacted,
which included provisions related to the accelerated approval pathway. Pursuant to FDORA, the FDA is authorized to require a post-approval study to be
underway prior to approval or within a specified time period following approval. FDORA also requires the FDA to specify conditions of any required post-
approval study, which may include milestones such as a target date of study completion and requires sponsors to submit progress reports for required post-
approval studies and any conditions required by the FDA not later than 180 days following approval and not less frequently than every 180 days thereafter
until completion or
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termination of the study. FDORA enables the FDA to initiate criminal prosecutions for the failure to conduct with due diligence a required post-approval study,
including a failure to meet any required conditions specified by the FDA or to submit timely reports.
Breakthrough Therapy Designation
The FDA is also required to expedite the development and review of the application for approval of drugs that are intended to treat a serious or life-
threatening disease or condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing
therapies on one or more clinically significant endpoints. Under the breakthrough therapy program, the sponsor of a new drug candidate may request that
the FDA designate the drug candidate for a specific indication as a breakthrough therapy concurrent with, or after, the filing of the IND for the drug candidate.
The FDA must determine if the drug candidate qualifies for breakthrough therapy designation within 60 days of receipt of the sponsor’s request.
Adaptive Pathways
The EMA has an adaptive pathways approach which allows for early and progressive patient access to a medicine in cases of high medical need.
To achieve this goal, several approaches are envisaged including for example identifying small populations with severe disease where a medicine’s benefit-
risk balance could be favorable or making more use of real-world data where appropriate to support clinical trial data. The adaptive pathways concept
applies primarily to treatments in areas of high medical need where it is difficult to collect data via traditional routes and where large clinical trials would
unnecessarily expose patients who are unlikely to benefit from the medicine. The approach builds on regulatory processes already in place within the
existing EU legal framework. These include: scientific advice; compassionate use; the conditional MA; patient registries and other pharmacovigilance tools
that allow collection of real-life data and development of a risk-management plan for each medicine.
A conditional MA may be granted prior to the submission of comprehensive clinical data if the benefit of the immediate availability on the market of
the product is deemed to outweigh the risk inherent in the fact that additional data are still required. In emergency situations, a MA for such medicinal
products may be granted also where comprehensive pre-clinical or pharmaceutical data have not been provided. Under this procedure a MA can be granted
as soon as sufficient data becomes available to demonstrate that the drug's benefits outweigh its risks, with safeguards and controls in place post-
authorization. This procedure can also be combined with a rolling review of data during the development of a promising medicine, to further expedite its
evaluation. Conditional MAs are typically subject to obligations that are reviewed annually. These include the obligation to complete ongoing studies, or to
conduct new studies, with a view to confirming that the risk-benefit balance is favorable. Conditional MAs are valid for one year and are renewable.
PRIME Program
The EMA launched its PRIME regulatory program to enhance support for the development of therapies that target an unmet medical need. The
initiative focuses on drugs that may offer a major therapeutic advantage over existing treatments, or benefit patients with no treatment options. These
therapies are considered priority medicines within the EU. Through PRIME, the EMA offers early, proactive and enhanced support to drug developers to
optimize the generation of robust data on a therapy’s benefits and risks and enable accelerated assessment of drug applications.
Regulation of Product Marketing and Promotion
A marketing approval authorizes commercial marketing of the drug with specific prescribing information for specific indications. As a condition of
NDA or BLA approval, the FDA may require a REMS, to help ensure that the benefits of the drug outweigh the potential risks. A REMS can include
medication guides, communication plans for healthcare professionals, and elements to assure safe use, such as special training or certification for
prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patient registries. Moreover, product approval may
require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if
compliance with regulatory standards is not maintained or problems are identified following initial marketing. Similar rules apply outside of the U.S. For
example, products approved in the EU may be subject to post-authorization requirements such as the obligation to perform post-authorization efficacy
studies (PAES) or post-authorization safety studies (PASS) imposed as conditions to the MA, or other Risk Minimization Measures (RMMs), such as
educational programs or controlled access programs, which may sometimes vary from one EU Member State to another.
Regulation of Manufacturing Standards
The FDA as well as other regulatory agencies around the world, regulate and inspect the equipment, facilities, laboratories and processes used in
the manufacturing and testing of products prior to granting approval to market products. If after receiving approval from the FDA and other agencies such as
the EC we make a material change in manufacturing equipment, location or process, additional regulatory review and approval may be required. We also
must adhere to cGMP regulations and product-specific regulations enforced by the FDA and other regulatory agencies through their facilities inspection
program. The FDA and
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other regulatory agencies around the world conduct regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an
initial approval.
Combination Products
Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a
device). Biologics/drugs and devices each have their own regulatory requirements, and combination products may have additional requirements. For
example, in the EU, if a device intended to administer a medicinal product is sold together with such medicinal product in such a way that they form a single
integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product is regulated as a
medicinal product. In addition, the relevant general safety and performance requirements established for medical devices by EU medical devices legislation
apply to the device component of such combination products. A number of our products qualify as combination products and are regulated under the
applicable framework, and we expect that a number of our pipeline product candidates will be evaluated for regulatory approval under such framework as
well.
Post-Approval Regulatory Requirements
Following approval, the FDA and the regulatory authorities around the world will impose certain post-approval requirements related to a product.
For instance, the FDA and European authorities closely regulate the post-approval marketing and promotion of approved products, including standards and
regulations for direct-to-consumer advertising (which is prohibited in the EU for prescription products such as our products), off-label promotion, industry-
sponsored scientific and educational activities and promotional activities involving the Internet. Moreover, if a company obtains original approval for a product
via an accelerated approval pathway, the company will be typically required to conduct a post-marketing confirmatory trial to verify and describe the clinical
benefit in support of full approval. An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of the marketing
approval for a product.
Approved products may be marketed only for the approved indications and in accordance with the provisions of the approved labeling. Changes to
some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, may
require a submission to and approval by the FDA or the EC, as applicable, before the change can be implemented. An NDA/BLA or MAA supplement for a
new indication typically requires clinical data similar to that in the original application, and similar procedures and actions in reviewing NDA/ BLA or MAA
supplements as in reviewing NDAs/BLAs and MAAs.
Adverse event reporting and submission of periodic reports is required following marketing approval. Either the FDA or the EC/EMA may also
require post-marketing testing, known as Phase 4 testing, a risk evaluation and mitigation strategy, and surveillance to monitor the effects of an approved
product or place conditions on an approval that could restrict the distribution or use of the product. In addition, quality control as well as the manufacture,
packaging, and labeling procedures must continue to conform to cGMPs after approval. Drug and biological product manufacturers and certain of their
subcontractors are subject to periodic unannounced inspections by the FDA, the EMA/NCAs, during which the inspectors audit manufacturing facilities to
assess compliance with cGMPs. Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with
regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered. In addition,
prescription drug manufacturers in the U.S. must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product
tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities and have procedures in place to identify and
properly handle suspect and illegitimate products. Similarly, in the EU, stringent rules have been introduced to fight medicine falsifications and to ensure that
the trade in medicines is subject to rigorous controls. Measures required to ensure that include: a unique identifier and an anti-tampering device on the outer
packaging of drugs, stringent rules on import of active pharmaceutical ingredients and record-keeping requirements for wholesale distributors.
Approval Regulation Outside of the U.S. and the EU
For marketing outside the U.S. and the EU, we are subject to non-U.S. regulatory requirements governing human clinical testing and marketing
approval for our products. These requirements vary by jurisdiction, can differ from those in the U.S. and the EU and may require us to perform additional
preclinical or clinical testing. The amount of time required to obtain necessary approvals may be longer or shorter than that required for FDA or EC approval.
In many countries outside of the U.S., approvals for pricing, coverage and reimbursement offered by third-party payers, including government payers and
private insurance plans, are also required.
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Other Regulation
Exclusivity for Biologics in the U.S.
The Biologics Price Competition and Innovation Act of 2009 (BPCIA), which was enacted as part of the Patient Protection and Affordable Care Act
of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (as amended, the PPACA), created an abbreviated approval pathway for
biological products that are demonstrated to be “biosimilar” or “interchangeable” with an FDA-licensed reference biological product. Biosimilarity sufficient to
reference a prior FDA-licensed product requires that there be no differences in conditions of use, route of administration, dosage form, and strength, and no
clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency. Biosimilarity must be shown
through analytical studies, animal studies, and at least one clinical study, absent a waiver from the Secretary of the U.S. Department of Health and Human
Services. In order to meet the higher hurdle of interchangeability, a sponsor must demonstrate that the biosimilar product can be expected to produce the
same clinical result as the reference product, and for a product that is administered more than once, that the risk of switching between the reference product
and biosimilar product is not greater than the risk of maintaining the patient on the reference product. The first biosimilar product was approved under the
BPCIA in 2015, and the first interchangeable product was approved in 2021. Complexities associated with the larger, and often more complex, structures of
biological products, as well as the process by which such products are manufactured, pose significant hurdles to implementation that are still being
evaluated by the FDA. A reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product and no application for a
biosimilar can be submitted for four years from the date of licensure of the reference product. The first biologic product submitted under the abbreviated
approval pathway that is determined to be interchangeable with the reference product has exclusivity against a finding of interchangeability for other
biologics for the same condition of use for the lesser of (i) one year after first commercial marketing of the first interchangeable biosimilar, (ii) eighteen
months after the first interchangeable biosimilar is approved if there is not patent challenge, (iii) eighteen months after resolution of a lawsuit over the patents
of the reference biologic in favor of the first interchangeable biosimilar applicant, or (iv) 42 months after the first interchangeable biosimilar’s application has
been approved if a patent lawsuit is ongoing within the 42-month period.
Data Exclusivity and Market Exclusivity in the EU
The EU provides opportunities for market and data exclusivity for all products containing a New Active Substance, or NAS (such as a chemical,
biological or radiopharmaceutical substance not previously authorized as a medicinal product in the EU), which have been granted an MA. These products
receive eight years of data exclusivity and an additional two years of market exclusivity. The data exclusivity period prevents generic or biosimilar applicants
from relying on the pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU
during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a
successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial MA of the reference product
in the EU. The overall ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the
MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to
bring a significant clinical benefit in comparison with existing therapies.
Orphan Drug Designation
Orphan drug designation is granted by the FDA and the EC to drugs intended to treat a rare disease or condition, which in the U.S. is defined as
having a prevalence of less than 200,000 individuals in the U.S. In the EU, orphan drug designation is available if a sponsor can establish: that the medicine
is intended for the diagnosis, prevention or treatment of (1) a life-threatening or chronically debilitating condition affecting no more than five in 10,000 people
in the EU, which is equivalent to around 250,000 people or fewer, or (2) a life-threatening, seriously debilitating or serious and chronic condition in the EU
and that without incentives derived from the orphan status, it is unlikely that the marketing of the medicinal product in the EU would generate sufficient return
to justify the necessary investment. For either of these criteria, the applicant must demonstrate that there exists no satisfactory method of diagnosis,
prevention or treatment of the condition in question that has been authorized in the EU or, if such method exists, the medicinal product will be of significant
benefit to those affected by that condition. Orphan drug designation must be requested before submitting a marketing application and, in the EU, it must be
maintained until the time of the granting of the MA. Orphan designation is indeed lost in the EU if it is established that the product no longer meets the
orphan criteria at the time a MA is granted for such product.
Orphan drug designation does not shorten the regulatory review and approval process. However, if an orphan drug later receives approval for the
indication for which it has designation, the relevant regulatory authority may not approve any other applications to market the same drug for the same
indication, except in very limited circumstances, for seven years in the U.S. and ten years in the EU (extendable to twelve years for medicines that have
complied with an agreed Pediatric Investigation Plan (PIP) pursuant to Regulation 1901/2006) and, in addition, a range of other benefits during the
development and regulatory review process are available in the EU, including scientific assistance for study protocols, authorization through the centralized
marketing authorization procedure covering all member countries and a reduction or elimination of registration and marketing authorization fees. Among the
benefits of orphan drug designation in the U.S. are tax credits for certain research and a waiver of the NDA/BLA
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application user fee. Orphan drug exclusive marketing rights may be lost under certain conditions, such as if the request for designation was materially
defective or if the manufacturer is unable to assure sufficient quantity of the drug. In the EU, a MA may be granted to a similar medicinal product with the
same orphan indication during the regulatory exclusivity period with the consent of the MA holder for the original orphan medicinal product or if the MA
holder of the original orphan medicinal product is unable to supply sufficient quantities. A MA may also be granted to a similar medicinal product with the
same orphan indication if the second applicant can establish that its medicinal product is safer, more effective or otherwise clinically superior to the original
orphan medicinal product. The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it can be demonstrated on
the basis of available evidence that the criteria for its designation as an orphan medicine are no longer satisfied, for example if the original orphan medicinal
product has become sufficiently profitable not to justify maintenance of market exclusivity.
Healthcare Reform
The U.S. federal and state governments continue to propose and pass legislation designed to regulate the healthcare industry, including legislation
that seeks to directly or indirectly regulate pharmaceutical drug pricing. For more information, see Item 1A. Risk Factors “Government healthcare reform
could increase our costs and adversely affect our revenue and results of operations.”
Other Regulatory Requirements
In addition to FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws have been applied to restrict
certain business and marketing practices in the pharmaceutical industry in recent years. These laws include anti-kickback, false claims, patient data privacy
and security, and transparency statutes and regulations.
The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to
induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under
Medicare, Medicaid or other federally financed healthcare programs. The PPACA amended the intent requirement of the federal Anti-Kickback and certain
other criminal healthcare fraud statutes such that a person or entity no longer needs to have actual knowledge of these statutes or specific intent to violate
them in order to commit a violation. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and
prescribers, purchasers and formulary managers on the other. Although there are a number of statutory exceptions and regulatory safe harbors protecting
certain common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that involve
remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor.
Federal false claims laws prohibit any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal
government, or knowingly making, or causing to be made, a false statement to have a false claim paid. The PPACA amended the statute so that the
government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent
claim for purposes of the false claims laws. Recently, several pharmaceutical and other healthcare companies have been prosecuted under these laws for
allegedly inflating drug prices they report to pricing services, which in turn are used by the government to set Medicare and Medicaid reimbursement rates,
and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, certain
marketing practices, including off-label promotion, may also violate false claims laws.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for, among other things,
executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. HIPAA, as amended by the Health
Information Technology for Economic and Clinical Health Act and their implementing regulations, also imposes obligations, including mandatory contractual
terms, on certain types of individuals and entities, with respect to safeguarding the privacy, security and transmission of individually identifiable health
information.
The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment
is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare &
Medicaid Services (CMS) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists,
podiatrists and chiropractors), physician assistants, certain types of advanced practice nurses and teaching hospitals, and applicable manufacturers and
applicable group purchasing organizations to report annually to CMS ownership and investment interests held by the physicians and their immediate family
members.
The majority of states also have statutes or regulations similar to the federal Anti-Kickback Statute and false claims laws, which apply to items and
services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payer. Several states now require
pharmaceutical companies to report expenses relating to the marketing and promotion of pharmaceutical products and to report gifts and payments to
individual physicians in these states while other states prohibit various other marketing-related activities. Other states require submission or disclosure of
certain pricing information. Still other states require the posting of information relating to clinical studies and their outcomes. In addition, states including
California, Connecticut,
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Nevada and Massachusetts require pharmaceutical companies to implement compliance programs or marketing codes. Currently, several additional states
are considering similar proposals. Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws face
civil penalties. Sanctions under these federal and state laws may include significant penalties, including administrative and criminal sanctions, civil monetary
penalties, damages, monetary fines, disgorgement, exclusion of a company from federal healthcare programs, integrity oversight and reporting obligations,
criminal fines, contractual damages, reputational harm, diminished profits and future earnings, curtailment of operations and imprisonment.
The U.S. Foreign Corrupt Practices Act (FCPA), to which we are subject, prohibits corporations and individuals from engaging in certain activities to
obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value
to any non-U.S. government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise
influence a person working in an official capacity. Similar laws exist in other countries, such as the U.K., that restrict improper payments to public and private
parties. Many countries have laws prohibiting these types of payments within the respective country. In the EU, for example, harmonized rules prohibit gifts,
pecuniary advantages or benefits in kind to Health Care Professionals (HCPs) unless they are inexpensive and relevant to the practice of medicine or
pharmacy. Similarly, strict rules apply to hospitality at sales promotion events. Based on these rules, a body of industry guidelines and sometimes national
laws in force in individual EU Member States has been introduced to fight improper payments or other transfers of value to HCPs, and in general
inducements that may have a broadly promotional character. Historically, pharmaceutical companies have been the target of FCPA and other anti-corruption
and similar investigations, as well as of wide media attention, sometimes resulting in significant penalties, image and other costs for such companies.
Pricing and Reimbursement
Because the course of treatment for patients using our products is expensive, sales of our products depend, in significant part, on the availability
and extent of coverage and reimbursement offered by third-party payers, including government payers and private insurance plans. Governments may
regulate access to, prices of or reimbursement levels for our products to control costs or to affect levels of use of our products, and private insurers may be
influenced by government reimbursement methodologies.
Third-party payers carefully review and increasingly challenge the prices charged for drugs, examine their medical necessity, and review their cost
effectiveness. Reimbursement rates from private companies vary depending on the third-party payer, the insurance plan and other factors. One payer’s
determination to provide coverage for a product does not assure that other payers will also provide coverage for the product. Moreover, the process for
determining whether a third-party payer will provide coverage for a product may be separate from the process for setting the price of a product or for
establishing the reimbursement rate that such a payer will pay for the product. Obtaining coverage and adequate reimbursement for our products may be
particularly difficult because of the higher prices often associated with drugs administered under the supervision of a physician. A payer’s decision to provide
coverage for a product does not imply that an adequate reimbursement rate will be approved. Adequate third-party reimbursement may not be available to
enable us to maintain high enough price levels to realize sufficient revenues from our investment in product development. In addition, emphasis on managed
care in the U.S. has increased and we expect will continue to increase the pressure on pharmaceutical pricing. Coverage policies and third-party
reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we or our
collaborators receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
Outside of the U.S. our products are paid for by a variety of payers, with governments being the primary source of payment. Reimbursement in the
EU and many other territories must be negotiated on a country-by-country basis and in many countries the product cannot be commercially launched until
pricing and/or reimbursement is approved. In many countries the government closely regulates drug pricing and reimbursement and often has a significant
discretion in determining whether a product will be reimbursed at all and, if it is, how much will be paid. Negotiating prices with governmental authorities can
delay commercialization of our products. Payers in many countries use a variety of cost-containment measures that can include referencing prices in other
countries and using those reference prices to set their own price, mandatory price cuts and rebates. This international patchwork of price regulation has led
to different prices across countries and some cross-border trade in our products from markets with lower prices. Even after a price is negotiated, countries
frequently request or require adjustments to the price and other concessions over time.
Government Pricing and Reimbursement Programs for Marketed Drugs in the U.S.
Medicaid, the 340B Drug Pricing Program, and Medicare
Federal law requires that a pharmaceutical manufacturer, as a condition of having its products receive federal reimbursement under Medicaid and
Medicare Part B, must pay rebates to state Medicaid programs for all units of its covered outpatient drugs dispensed to Medicaid beneficiaries and paid for
by a state Medicaid program under either a fee-for-service arrangement or through a managed care organization. This federal requirement is effectuated
through a Medicaid drug rebate agreement between the manufacturer and the Secretary of Health and Human Services. CMS administers the Medicaid drug
rebate agreements, which provide, among other things, that the drug manufacturer will pay rebates to each state Medicaid agency
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on a quarterly basis and report certain price information on a monthly and quarterly basis. The rebates are based on prices reported to CMS by
manufacturers for their covered outpatient drugs. For non-innovator products, generally generic drugs marketed under abbreviated new drug applications
(referred to as ANDAs), the rebate amount is 13% of the average manufacturer price (AMP) for the quarter. The AMP is the weighted average of prices paid
to the manufacturer (1) directly by retail community pharmacies and (2) by wholesalers for drugs distributed to retail community pharmacies. For innovator
products (i.e., drugs that are marketed under NDAs or BLAs), the rebate amount is the greater of 23.1% of the AMP for the quarter or the difference between
such AMP and the best price for that same quarter. The best price is essentially the lowest price available to non-governmental entities. Innovator products
may also be subject to an additional rebate that is based on the amount, if any, by which the product’s AMP for a given quarter exceeds the inflation-adjusted
baseline AMP, which for most drugs is the AMP for the first full quarter after launch. Since 2017, non-innovator products are also subject to an additional
rebate. To date, the rebate amount for a drug has been capped at 100% of the AMP; however, effective January 1, 2024, this cap will be eliminated, which
means that a manufacturer could pay a rebate amount on a unit of the drug that is greater than the average price the manufacturer receives for the drug.
The terms of participation in the Medicaid drug rebate program impose an obligation to correct the prices reported in previous quarters, as may be
necessary. Any such corrections could result in additional or lesser rebate liability, depending on the direction of the correction. In addition to retroactive
rebates, if a manufacturer were found to have knowingly submitted false information to the government, federal law provides for civil monetary penalties for
failing to provide required information, late submission of required information, and false information.
A manufacturer must also participate in a federal program known as the 340B drug pricing program in order for federal funds to be available to pay
for the manufacturer’s drugs under Medicaid and Medicare Part B. Under this program, the participating manufacturer agrees to charge certain safety net
healthcare providers no more than an established discounted price for its covered outpatient drugs. The formula for determining the discounted price is
defined by statute and is based on the AMP and the unit rebate amount as calculated under the Medicaid drug rebate program, discussed above.
Manufacturers are required to report pricing information to the Health Resources and Services Administration (HRSA) on a quarterly basis. HRSA has also
issued regulations relating to the calculation of the ceiling price as well as imposition of civil monetary penalties for each instance of knowingly and
intentionally overcharging a 340B covered entity.
Federal law also requires that manufacturers report data on a quarterly basis to CMS regarding the pricing of drugs that are separately
reimbursable under Medicare Part B. These are generally drugs, such as injectable products, that are administered “incident to” a physician service and are
not generally self-administered. The pricing information submitted by manufacturers is the basis for reimbursement to physicians and suppliers for drugs
covered under Medicare Part B. As with the Medicaid drug rebate program, federal law provides for civil monetary penalties for failing to provide required
information, late submission of required information, and false information.
Medicare Part D provides prescription drug benefits for seniors and people with disabilities. Medicare Part D enrollees once had a gap in their
coverage (between the initial coverage limit and the point at which catastrophic coverage begins) where Medicare did not cover their prescription drug costs,
known as the coverage gap. However, beginning in 2019, Medicare Part D enrollees paid 25% of brand drug costs after they reached the initial coverage
limit - the same percentage they were responsible for before they reached that limit - thereby closing the coverage gap from the enrollee’s point of view. Most
of the cost of closing the coverage gap is being borne by innovator companies and the government through subsidies. Each manufacturer of drugs approved
under NDAs or BLAs is required to enter into a Medicare Part D coverage gap discount agreement and provide a 70% discount on those drugs dispensed to
Medicare Part D enrollees in the coverage gap, in order for its drugs to be reimbursed by Medicare Part D. Beginning in 2025, the Inflation Reduction Act
(IRA) eliminates the coverage gap under Medicare Part D by significantly lowering the enrollee maximum out-of-pocket cost and requiring manufacturers to
subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket
maximum, and 20% once the out-of-pocket maximum has been reached. Although these discounts represent a lower percentage of enrollees’ costs than the
current discounts required below the out-of-pocket maximum (that is, in the coverage gap phase of Part D coverage), the new manufacturer contribution
required above the out-of-pocket maximum could be considerable for very high-cost patients and the total contributions by manufacturers to a Part D
enrollee’s drug expenses may exceed those currently provided.
The IRA will also allow the U.S. Department of Health and Human Services (HHS) to negotiate the selling price of certain drugs and biologics that
CMS reimburses under Medicare Part B and Part D, although only high-expenditure single-source drugs that have been approved for at least 7 years (11
years for biologics) can be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year. The negotiated prices,
which will first become effective in 2026, will be capped at a statutory ceiling price. Beginning in October 2022 for Medicare Part D and January 2023 for
Medicare Part B, the IRA will also penalize drug manufacturers that increase prices of Medicare Part D and Part B drugs at a rate greater than the rate of
inflation.
U.S. Federal Contracting and Pricing Requirements
Manufacturers are also required to make their covered drugs, which are generally drugs approved under NDAs or BLAs, available to authorized
users of the Federal Supply Schedule (FSS) of the General Services Administration. The law also requires manufacturers to offer deeply discounted FSS
contract pricing for purchases of their covered drugs by the Department of Veterans
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Affairs, the Department of Defense, the Coast Guard, and the Public Health Service (including the Indian Health Service) in order for federal funding to be
available for reimbursement or purchase of the manufacturer’s drugs under certain federal programs. FSS pricing to those four federal agencies for covered
drugs must be no more than the Federal Ceiling Price (FCP), which is at least 24% below the Non-Federal Average Manufacturer Price (Non-FAMP) for the
prior year. The Non-FAMP is the average price for covered drugs sold to wholesalers or other middlemen, net of any price reductions.
The accuracy of a manufacturer’s reported Non-FAMPs, FCPs, or FSS contract prices may be audited by the government. Among the remedies
available to the government for inaccuracies is recoupment of any overcharges to the four specified federal agencies based on those inaccuracies. If a
manufacturer were found to have knowingly reported false prices, in addition to other penalties available to the government, the law provides for significant
civil monetary penalties per incorrect item. Finally, manufacturers are required to disclose in FSS contract proposals all commercial pricing that is equal to or
less than the proposed FSS pricing, and subsequent to award of an FSS contract, manufacturers are required to monitor certain commercial price reductions
and extend commensurate price reductions to the government, under the terms of the FSS contract Price Reductions Clause. Among the remedies available
to the government for any failure to properly disclose commercial pricing and/or to extend FSS contract price reductions is recoupment of any FSS
overcharges that may result from such omissions.
Disclosure of Clinical Trial Information
Sponsors of clinical trials of FDA-regulated products, including drugs and biologics, are required to register and disclose certain clinical trial
information. Information related to the product, patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial
are then made public as part of the registration. Sponsors are also obligated to discuss the results of their clinical trials after completion. In certain
circumstances, disclosure of the results of these trials can be delayed for up to two years after the date of completion of the trial. Competitors may use this
publicly available information to gain knowledge regarding the progress of development programs. In the EU there is an increasing trend requiring public
disclosure of development data, in particular clinical trial data. These data were traditionally regarded as Confidential Commercial Information (CCI);
however, under policies adopted in the EU, clinical study data submitted to the EMA in MAAs, including preclinical data, and patient level data, may be
subject to public disclosure. This is confirmed in the CTR, the new EU legislation on clinical trials, according to which clinical trial applications and all the
related documentation are uploaded and stored in the Clinical Trials Information System (CTIS) which is managed by the EMA. Confirming the transparency
principle, the CTR provides that the information stored in such system is publicly accessible unless confidentiality is justified on the basis of a limited set of
exceptions. These exceptions, which are to be interpreted narrowly in the EU, include the protection of CCI, in particular through taking into account the
status of the MA for the applicable product; however, CCI is overridden in those cases where the authorities conclude that there is an overriding public
interest in disclosure. Case law of the Court of Justice of the EU has also confirmed the absence of a general presumption of confidentiality over documents
containing clinical and preclinical data provided to the EMA in support of a MAA.
Pediatric Indications
In the U.S., under the Pediatric Research Equity Act of 2007 (PREA), NDAs or BLAs or supplements to NDAs or BLAs must contain data to assess
the safety and effectiveness of the drug for the claimed indication(s) in all relevant pediatric subpopulations and to support dosing and administration for
each pediatric subpopulation for which the drug is safe and effective. The FDA may grant deferrals for submission of data or full or partial waivers. Unless
otherwise required by statute or regulation, PREA does not apply to any drug for an indication for which orphan drug designation has been granted. The Best
Pharmaceuticals for Children Act (BPCA) provides sponsors of NDAs with an additional six-month period of market exclusivity for all unexpired patent or
non-patent exclusivity on all forms of the drug containing the active moiety if the sponsor submits results of pediatric studies specifically requested by the
FDA under BPCA within required timeframes. The BPCIA provides sponsors of BLAs an additional six-month extension for all unexpired non-patent market
exclusivity on all forms of the biological containing the active moiety pursuant to the BPCA if the conditions under the BPCA are met.
In the EU, companies developing a new medicinal product must agree to a PIP with the EMA and must conduct pediatric clinical trials in
accordance with that PIP, unless a deferral or waiver is granted by the EMA on request by the applicant (e.g., because the relevant disease or condition
occurs only in adults). The PIP requirement also applies when a MA holder intends to add a new indication, pharmaceutical form or route of administration
for a medicinal product that has already been authorized. The MAA for the product must include the results of pediatric clinical trials conducted in
accordance with the PIP, unless a waiver applies, or a deferral has been granted, in which case the pediatric clinical trials must be completed at a later date.
Once all the studies and measures agreed have been conducted in accordance with the PIP, products are eligible for a six -month extension of the protection
under a supplementary protection certificate (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two -year extension of
the orphan market exclusivity. This pediatric reward is granted subject to specific conditions. These conditions include that the applicant demonstrates
having complied with all the measures contained in the PIP, that the summary of product characteristics, and if appropriate the package leaflet, reflects the
results of studies conducted in compliance with such PIP, and that the product is authorized in all Member States. The rewards for conducting studies in the
pediatric population can be granted irrespective of the fact that the information generated in compliance with the agreed PIP fails to lead to the authorization
of a pediatric indication.
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Privacy and Security Legislation
In the ordinary course of our business, we may process personal or sensitive data. Accordingly, we are, or may become, subject to numerous data
privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, and industry standards related to data privacy,
security, and protection. Such obligations may include, without limitation, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018
(CCPA), the Canadian Personal Information Protection and Electronic Documents Act, the European Union’s General Data Protection Regulation 2016/679
(EU GDPR), the EU GDPR as it forms part of United Kingdom (UK) law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (UK GDPR).
The legislative and regulatory environments regarding privacy and data protection are continually evolving and developing, in response to
increasing global attention. In the U.S., for example, we are subject to the CCPA along with the California Privacy Rights Act of 2020 (CPRA). The CCPA
imposes obligations on covered businesses to provide specific disclosures related to a business’s collecting, using, and disclosing personal data and to
respond to certain requests from California residents related to their personal data (for example, requests to know of the business’s personal data
processing activities, to delete the individual’s personal data, and to opt out of certain personal data disclosures). Also, the CCPA provides for civil penalties
and a private right of action for data breaches which may include an award of statutory damages. In addition, the CPRA, effective January 1, 2023,
expanded the CCPA. The CPRA, among other things, gives California residents the ability to limit use of certain sensitive personal data, establish restrictions
on personal data retention, expands the types of data breaches that are subject to the CCPA’s private right of action, and establishes a new California
Privacy Protection Agency to implement and enforce the new law.
Other jurisdictions where we operate have enacted or proposed similar legislation and/or regulations. Several states within the United States have
enacted or proposed data privacy laws. Additionally, we are, or may become, subject to various U.S. federal and state consumer protection laws which
require us to publish statements that accurately and fairly describe how we handle personal data and choices individuals may have about the way we handle
their personal data.
We are also subject to the EU’s General Data Protection Regulation GDPR, which requires that personal data is only collected for specified, explicit
and legal purposes as set out in the GDPR or local laws, and the data may then only be processed in a manner consistent with those purposes. The
personal data collected and processed must be adequate, relevant and not excessive in relation to the purposes for which it is collected and processed, it
must be held securely, not transferred outside of the EEA (unless certain steps are taken to ensure an adequate level of protection), and must not be
retained for longer than necessary for the purposes for which it was collected. The GDPR also requires companies processing personal data to implement
adequate technical measures in order to ensure the most appropriate level of security which may vary depending on different factors such as the categories
of processed personal data, the state of the art, the costs of implementation and the nature, scope, context and purposes of processing as well as the risk of
varying likelihood and severity for the rights and freedoms of natural persons. In addition, the GDPR requires companies processing personal data to take
certain organizational steps to ensure that they have adequate records, policies, security, training and governance frameworks in place to ensure the
protection of data subject rights, including as required to respond to complaints and requests from data subjects. For example, the GDPR requires us to
make more detailed disclosures to data subjects, requires disclosure of the legal basis on which we can process personal data, provides for conditions under
which a valid consent for processing can be obtained, requires the appointment of a data protection officer where sensitive personal data (i.e., health data) is
processed on a large scale, imposes mandatory data breach notification throughout the EEA and imposes additional obligations when contracting with
service providers or partners. In addition, to the extent a company processes, controls or otherwise uses “special category” of personal data (including
patients’ health or medical information, genetic information and biometric information), more stringent rules apply, further limiting the circumstances and the
manner in which a company is legally permitted to process that data.
Failure to comply with these laws could result in significant penalties, including, under GDPR, fines of up to 20 million Euro or 4% of the total
worldwide annual turnover of the preceding financial year, whichever is higher. The CCPA and EU GDPR are examples of the increasingly stringent and
evolving regulatory frameworks related to personal data processing that may increase compliance obligations and exposure for any noncompliance.
Human Capital
As of December 31, 2022, we had 3,082 full-time employees worldwide, of whom 1,343 were in operations, 736 were in research and development,
495 were in sales and marketing and 508 were in administration. Of the 3,082 full-time employees as of December 31, 2022, 2,066 employees were in the
U.S. and Canada, and 1,016 employees were in other non-U.S. countries, including 818 in Europe and the Middle East, 129 in Latin America and 69 in Asia
Pacific. We also leverage temporary workers to fill short-term positions for our business and manufacturing needs. A significant portion of our employee base
in the U.S. and Ireland works onsite supporting manufacturing and laboratory operations. As restrictions from the COVID-19 pandemic have eased,
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a significant portion of our global workforce who worked remotely during the pandemic has made a return to their respective office locations on a hybrid
basis, with a small number of employees continuing to fully work remotely.
On October 6, 2022, we announced a plan to simplify our organization, which included a planned reduction in headcount of approximately 120
employees (representing approximately 4% of the Company’s global workforce), most of whom were from the Company's U.S. operations.
Diversity, Equity and Inclusion
At BioMarin, prejudice, racism and intolerance are unacceptable. We are committed to diversity, equity and inclusion (DEI) across all aspects of our
organization, including hiring, promotion and development practices. At the direction of BioMarin's senior leadership team, our human resources department
has implemented policies and programs to foster DEI at all levels of the organization. In addition, the Corporate Governance and Nominating and
Compensation Committees of our Board of Directors regularly receive reports on our DEI policies and programs and offer valuable insights and
recommendations to management in addition to providing appropriate oversight.
As of December 31, 2022, racial and ethnic minorities represented 47% of our employees in the U.S. Globally, 50% of our workforce were women
and 47% of our positions at director-level and above were held by women. We are committed to continuing our ongoing efforts to ensure diversity in all
positions, including leadership.
We remain steadfast in our commitment to fostering a community that reflects equality and inclusiveness and working towards making BioMarin a
place where every employee feels heard, respected and valued. This commitment is a cultural value, and we believe incorporating and encouraging different
perspectives from employees of varied backgrounds and experiences helps us better serve our patients, achieve our business goals and objectives and
provide employees with a fulfilling work experience. Since 2020, BioMarin’s DEI Employee Advisory Committee has helped to define our DEI roadmap and
ensure that perspectives from employees of different age, gender, sexual orientation, race, ethnicity, tenure, level and location are considered in how we
build the most inclusive environment. We also continue to support and increase the number of our employee resource groups that build community for
employees from underrepresented groups. In addition, our foundational DEI training is required for all employees, with a 100% global participation rate in
2022, and we offer opportunities for advanced DEI training as well.
We are honored to be recognized as a company of choice. In 2022, we were recognized for the second year in a row as a Best Place to Work for
lesbian, gay, bisexual, transgender and queer (LGBTQ+) equality by the Human Rights Campaign, scoring 100% on their Corporate Equality Index, one of
the foremost benchmarking surveys and reports in the U.S. measuring corporate policies and practices related to LGBTQ+ workplace equality. In JUST
Capital’s America’s Most JUST Companies 2023 rankings, our overall rank was eight out of 41 in our industry, and our “Workers” rank, which is intended to
measure how a company invests in its employees, was 29 out of 951 companies across all industries and 4 out of 41 pharmaceutical and biotechnology
companies.
Compensation, Benefits and Well-being
We offer competitive compensation and benefits in order to attract and retain excellent employees and support their overall well-being. Our total
rewards compensation package includes market-competitive salary, the potential to earn bonuses or sales commissions, equity, healthcare benefits,
retirement savings plans, paid time off and family leave, wellness programs, free flu vaccinations and an Employee Assistance Program and other mental
health services.
We believe employees should be paid for the value of their work, regardless of race, ethnicity, gender or other protected characteristics. To this end,
we benchmark and tie compensation to market data as well as to an employee’s experience, function, and performance. We regularly review our workforce
compensation practices and strive for equity. Specifically, we partner with independent, third-party experts to conduct a regular and detailed pay equity
assessment to determine whether gender and race/ethnicity have a significant impact on pay levels across the organization. This pay equity analysis is
conducted on an employee’s total compensation, including base pay, bonus and equity. If we identify any pay gap across the organization, we typically make
adjustments to mitigate such gaps. Our managers also receive training in how to recognize and prevent discrimination in hiring, performance management
and compensation decisions.
Professional Growth and Development
We help our employees develop the skills and capabilities to support BioMarin’s growth and innovation. We continually invest in our employees’
career growth and provide them with a wide range of development opportunities, including face-to-face, virtual and self-directed learning, mentoring, mobile
coaching and external development. We offer our employees career-specific training and resources and support development opportunities through
company sponsored programs in addition to our tuition
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reimbursement program. We also provide our high-potential employees with a variety of leadership coaching and management programs.
Patient and Community Connections
We are striving to support our local communities around the world by developing programs that inspire and enrich both our patient populations and
the areas where we live and work. We actively engage with underrepresented populations through a variety of outreach and programs. We collaborate with
Biotech Partners, a non-profit organization in the San Francisco Bay Area focused on helping students who are underrepresented in the biotechnology field
to gain experience through classroom instruction and paid internships. We also partner with Health Career Connection, a national non-profit that prepares
the next generation of diverse, transformational health, equity and racial justice leaders by providing promising undergraduate college students from
underrepresented backgrounds and under-resourced communities with paid internship programs, health equity scholars programs and alumni professional
development initiatives. In addition, we award annual scholarships to students living with rare disease through our Rare Scholars program.
Other Information
We were incorporated in Delaware in October 1996. Our principal executive offices are located at 770 Lindaro Street, San Rafael, California 94901
and our telephone number is (415) 506-6700. Our annual reports on Form 10-K, quarterly reports on Form 10-Q, proxy statements, current reports on Form
8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the
Exchange Act) are available free of charge at www.bmrn.com as soon as reasonably practicable after electronically filing such reports with the Security and
Exchange Commission (the SEC). Such reports and other information may be accessed through the SEC’s website at www.sec.gov. Information contained in
our website is not part of this or any other report that we file with or furnish to the SEC.
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Item 1A. Risk Factors
An investment in our securities involves a high degree of risk. We operate in a dynamic and rapidly changing industry that involves numerous risks
and uncertainties. The risks and uncertainties described below are not the only ones we face. Other risks and uncertainties, including those that we do not
currently consider material, may impair our business. If any of the risks discussed below actually occur, our business, financial condition, operating results or
cash flows could be materially adversely affected. This could cause the value of our securities to decline, and you may lose all or part of your investment.
Business and Operational Risks
If we fail to obtain and maintain an adequate level of coverage and reimbursement for our products by third-party payers, the sales of our
products would be adversely affected or there may be no commercially viable markets for our products.
The course of treatment for patients using our products is expensive. For all our products except ROCTAVIAN, we expect patients to need
treatment for extended periods, and for some products throughout the lifetimes of the patients. We expect that most families of patients will not be capable of
paying for this treatment themselves. There will be no commercially viable market for our products without coverage and reimbursement from third-party
payers. Additionally, even if there is a commercially viable market, if the level of reimbursement is below our expectations, our revenues and gross margin
will be adversely affected.
Third-party payers, such as government or private healthcare insurers, carefully review and increasingly challenge the prices charged for drugs.
Reimbursement rates from private companies vary depending on the third-party payer, the insurance plan and other factors. Obtaining coverage and
adequate reimbursement for our products may be particularly difficult because of the higher prices often associated with drugs administered under the
supervision of a physician. Reimbursement systems in international markets vary significantly by country and by region, and reimbursement approvals must
be obtained on a country-by-country basis.
Government authorities and other third-party payers are developing increasingly sophisticated methods of controlling healthcare costs, such as by
limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payers are requiring that drug companies provide
them with predetermined discounts from list prices as a condition of coverage, are using restrictive formularies and preferred drug lists to leverage greater
discounts in competitive classes, and are challenging the prices charged for medical products. Further, no uniform policy requirement for coverage and
reimbursement for drug products exists among third-party payers in the U.S. Therefore, coverage and reimbursement for drug products can differ
significantly from payer to payer. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide
scientific and clinical support for the use of our products to each payer separately, with no assurance that coverage and adequate reimbursement will be
applied consistently or obtained in the first instance.
We cannot be sure that coverage and reimbursement will be available for any product that we commercialize or will continue to be available for any
product that we have commercialized and, if reimbursement is available, what the level of reimbursement will be. Even if favorable coverage and
reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement
rates may be implemented in the future. Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which we
obtain marketing approval. If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not successfully
commercialize any product candidate for which we obtain marketing approval or continue to market any product that has already been commercialized.
Reimbursement in the European Union (EU) and many other territories must be negotiated on a country-by-country basis, and in many countries
the product cannot be commercially launched until pricing and/or reimbursement is approved. The timing to complete the negotiation process in each country
is highly uncertain, and in some countries, we expect that it will exceed 12 months. Even after a price is negotiated, countries frequently request or require
reductions to the price and other concessions over time.
For our future products, we will not know what the reimbursement rates will be until we are ready to market the product and we actually negotiate
the rates. If we are unable to obtain sufficiently high reimbursement rates for our products, they may not be commercially viable or our future revenues and
gross margin may be adversely affected.
Because the target patient populations for our products are relatively small, we must achieve significant market share and maintain high
per-patient prices for our products to achieve and maintain profitability.
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All of our products target diseases with relatively small patient populations. Our two newest products, VOXZOGO and ROCTAVIAN, address
potentially larger patient populations than most of our other products; however, their market sizes are considerably smaller than many drugs marketed by
other pharmaceutical and biotechnology companies. As a result, our per-patient prices must be relatively high in order to recover our development and
manufacturing costs and achieve and maintain profitability. For BRINEURA, NAGLAZYME and VIMIZIM in particular, we must market worldwide to achieve
significant market penetration of the product. In addition, because the number of potential patients in each disease population is small, it is not only important
to find patients who begin therapy to achieve significant market penetration of the product, but we also need to be able to maintain these patients on therapy
for an extended period of time. Due to the expected costs of treatment for our products, we may be unable to maintain or obtain sufficient market share at a
price high enough to justify our product development efforts and manufacturing expenses.
If we fail to compete successfully with respect to product sales, we may be unable to generate sufficient sales to recover our expenses
related to the development of a product program or to justify continued marketing of a product and our revenues could be adversely affected.
Our competitors may develop, manufacture and market products that are more effective or less expensive than ours. They may also obtain
regulatory approvals for their products faster than we can obtain them (including those products with orphan drug designation, which may prevent us from
marketing our product entirely) or commercialize their products before we do. With respect to ROCTAVIAN, which has been conditionally approved in the EU
and may be approved in the U.S. and other markets in the future, we face a highly developed and competitive market for hemophilia A treatments. As we
commercialize ROCTAVIAN, we may face intense competition from large pharmaceutical companies with extensive resources and established relationships
in the hemophilia A community. If we do not compete successfully, our revenues would be adversely affected, and we may be unable to generate sufficient
sales to recover our expenses related to the development of a product program or to justify continued marketing of a product.
Changes in methods of treatment of disease could reduce demand for our products and adversely affect revenues.
Even if our product candidates are approved, if doctors elect a course of treatment which does not include our products, this decision would reduce
demand for our products and adversely affect revenues. For example, if gene therapy becomes widely used as a treatment of genetic diseases, the use of
enzyme replacement therapy, such as ALDURAZYME, NAGLAZYME, and VIMIZIM in MPS diseases, could be greatly reduced. Changes in treatment
method can be caused by the introduction of other companies’ products or the development of new technologies or surgical procedures which may not
directly compete with ours, but which have the effect of changing how doctors decide to treat a disease.
If we fail to develop new products and product candidates or compete successfully with respect to acquisitions, joint ventures, licenses
or other collaboration opportunities, our ability to continue to expand our product pipeline and our growth and development would be impaired.
Our future growth and development depend in part on our ability to successfully develop new products from our research and development
activities. The development of biopharmaceutical products is very expensive and time intensive and involves a great degree of risk. The outcomes of
research and development programs, especially for innovative biopharmaceuticals, are inherently uncertain and may not result in the commercialization of
any products.
Our competitors compete with us to attract organizations for acquisitions, joint ventures, licensing arrangements or other collaborations. To date,
several of our former and current product programs have been acquired through acquisitions and several of our former and current product programs have
been developed through licensing or collaborative arrangements, such as ALDURAZYME, KUVAN and NAGLAZYME. These collaborations include licensing
proprietary technology from, and other relationships with, academic research institutions. Our future success will depend, in part, on our ability to identify
additional opportunities and to successfully enter into partnering or acquisition agreements for those opportunities. If our competitors successfully enter into
partnering arrangements or license agreements with academic research institutions, we will then be precluded from pursuing those specific opportunities.
Because each of these opportunities is unique, we may not be able to find a substitute. Several pharmaceutical and biotechnology companies have already
established themselves in the field of genetic diseases. These companies have already begun many drug development programs, some of which may target
diseases that we are also targeting, and have already entered into partnering and licensing arrangements with academic research institutions, reducing the
pool of available opportunities.
Universities and public and private research institutions also compete with us. While these organizations primarily have educational or basic
research objectives, they may develop proprietary technology and acquire patents that we may need for the development of our product candidates. We will
attempt to license this proprietary technology, if available. These licenses may not be available to us on acceptable terms, if at all. If we are unable to
compete successfully with respect to acquisitions, joint venture and other collaboration opportunities, we may be limited in our ability to develop new
products and to continue to expand our product pipeline.
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The sale of generic versions of KUVAN by generic manufacturers has adversely affected and will continue to adversely affect our
revenues and may cause a decline in KUVAN revenues faster than expected.
Generic versions of KUVAN are available in several countries around the world, including multiple generic versions in the U.S. This generic
competition has adversely affected and will continue to adversely affect our revenues from KUVAN, and we cannot accurately predict the rate of decline of
KUVAN revenues in these countries. We are also aware that manufacturers are challenging our patent portfolio related to KUVAN in several jurisdictions,
and several generic versions of KUVAN have been approved either centrally by the European Medicines Agency (EMA) or on a country-by-country basis
throughout the EU. If these patent challenges are successful, or if a manufacturer chooses to offer a generic version of KUVAN, notwithstanding our existing
patents, our revenues from KUVAN may decline faster than expected.
If we do not achieve our projected development goals in the timeframes we announce or fail to achieve such goals, the
commercialization of our product candidates may be delayed or never occur and the credibility of our management may be adversely affected
and, as a result, our stock price may decline.
For planning purposes, we estimate the timing of the accomplishment of various scientific, clinical, regulatory and other product development goals,
which we sometimes refer to as milestones. These milestones may include the commencement or completion of scientific studies and clinical trials and the
submission of regulatory filings. From time to time, we publicly announce the expected timing of some of these milestones. All of these milestones are based
on a variety of assumptions. The actual timing of these milestones can vary dramatically compared to our estimates or the milestones may never be
achieved, in many cases for reasons beyond our control. For example, in 2021 and early 2022, we announced that we planned to resubmit our Biologics
License Application (BLA) for ROCTAVIAN to the Food and Drug Administration (FDA) in the first half of 2022; however, we did not file the BLA until the third
quarter of 2022 due to the additional time we needed to include supplemental information and analyses of data requested by the FDA. If we do not meet
development milestones as publicly announced, the commercialization of our products may be delayed or never occur and the credibility of our management
may be adversely affected and, as a result, our stock price may decline.
We have in the past and may in the future enter into licensing arrangements, and we may not realize the benefits of such licensing
arrangements.
We have in the past and may in the future enter into licensing arrangements with third parties. It is possible that we may not achieve financial or
strategic benefits that justify a specific license, or we may otherwise not realize the benefits of such licensing arrangement. Further, licensing arrangements
impose various diligence, milestone and royalty payment and other obligations on us. If we fail to comply with our obligations under any current or future
licenses, our licensors may have the right to terminate these license agreements, which could harm our business prospects, financial condition and results of
operations. Additionally, counterparties to our license agreements have in the past alleged and may in the future allege that we have breached a license
agreement, which can result in litigation or other disputes that can divert management’s attention away from our business and require us to expend
resources, as well as potentially having to negotiate new or reinstated licenses with less favorable terms. Any such situation could adversely affect our
business, financial condition, and results of operations.
Regulatory Risks
If we fail to obtain regulatory approval to commercially market and sell our product candidates, or if approval of our product candidates
is delayed, we will be unable to generate revenues from the sale of these product candidates, our potential for generating positive cash flow will
be diminished, and the capital necessary to fund our operations will increase.
We must obtain regulatory approval to market and sell our product candidates. For example, in the U.S., we must obtain FDA approval for each
product candidate that we intend to commercialize, and in the EU, we must obtain approval from the European Commission (EC), based on the opinion of
the Committee for Medicinal Products for Human Use (CHMP) of the EMA. The FDA and EC approval processes are typically lengthy and expensive, and
approval is never certain. To obtain regulatory approval, we must first show that our product candidates are safe and effective for target indications through
preclinical studies and clinical trials. Preclinical studies and clinical development are long, expensive and uncertain processes. Completion of clinical trials
may take several years, and failure may occur at any stage of development. The length of time required varies substantially according to the type,
complexity, novelty and intended use of a product candidate. Interim results of a preclinical test or clinical trial do not necessarily predict final results, and
acceptable results in early clinical trials may not be repeated in later clinical trials. Accordingly, there are no assurances that we will obtain regulatory
approval for any of our product candidates. Furthermore, there can be no assurance that approval of one of our product candidates by one regulatory
authority will mean that other authorities will also approve the same product candidate. For example, the EC’s conditional approval of ROCTAVIAN in August
2022 does not guarantee that the FDA will approve the same drug. Similarly, in the EU, a positive CHMP opinion for approval of a product candidate does
not guarantee that the EC will approve a drug. Moreover, regulatory authorities may approve a product candidate for fewer or more limited indications than
requested. In addition, regulatory authorities may not approve the labeling claims that are necessary or desirable for the successful commercialization of our
product candidates.
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We have had fewer interactions with regulatory authorities outside the U.S. and the EU as compared to our interactions with the FDA and EMA. The
approval procedures vary among countries and can involve additional clinical testing, and the time required to obtain approval may differ from that required
to obtain FDA or EC approval. Moreover, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries. Approval
by the FDA or EC does not ensure approval by regulatory authorities in other countries, and approval by one or more non-U.S. regulatory authorities does
not ensure approval by regulatory authorities in other non-U.S. countries or by the FDA or EC. However, a failure or delay in obtaining regulatory approval in
one country may have a negative effect on the regulatory process in others. The non-U.S. regulatory approval process may include all of the risks associated
with obtaining FDA or EC approval. We may not obtain non-U.S. regulatory approvals on a timely basis, if at all. We may not be able to file for regulatory
approvals and even if we file, we may not receive necessary approvals to commercialize our product candidates in any market.
We also rely on independent third-party CROs to file some of our non-U.S. marketing applications, and while we keep a close oversight on the
activities we delegate to CROs, important aspects of the services performed for us by the CROs are out of our direct control. If we fail to adequately manage
our CROs, if the CRO elects to prioritize work on our projects below other projects or if there is any dispute or disruption in our relationship with our CROs,
the filing of our applications may be delayed.
Although the FDA and the EMA have programs to facilitate expedited development and accelerated approval processes, the timelines agreed under
legislative goals or mandated by regulations are subject to the possibility of substantial delays. Accordingly, even if any of our applications receives a
designation to facilitate expedited development and accelerated approval processes, these designations may not result in faster review or approval for our
product candidates compared to product candidates considered for approval under conventional procedures and, in any event, do not assure ultimate
approval of our product candidates by regulatory authorities. In addition, the FDA, the EMA and other comparable international regulatory authorities have
substantial discretion over the approval process for pharmaceutical products. These regulatory agencies may not agree that we have demonstrated the
requisite level of product safety and efficacy to grant approval and may require, and in the past have required, additional data. If we fail to obtain regulatory
approval for our product candidates, we will be unable to market and sell those product candidates, which would have a negative effect on our business and
financial condition.
Regulatory agencies and the new requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform
additional or larger studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and
commercialization of our treatment candidate or lead to significant post-approval studies, limitations or restrictions. For example, on August 18, 2020, the
FDA issued a Complete Response Letter (CRL) to our BLA for ROCTAVIAN for the treatment of adults with severe hemophilia A. In the CRL, the FDA
introduced a new request for two-year follow-up safety and efficacy data on all study participants from our ongoing Phase 3 study of ROCTAVIAN. In January
2022, we announced results from the requested two-year data analysis from our Phase 3 study. In the third quarter of 2022, we resubmitted our BLA, and
the FDA subsequently accepted our submission with a Prescription Drug User Fee Act (PDUFA) target action date of March 31, 2023. Typically, BLA
resubmissions are followed by a six-month review procedure. However, we anticipate three additional months of review may be necessary based on the data
read-out we announced on January 8, 2023.
In addition, some of our product candidates are intended to be used in combination with a medical device, such as an injector or other delivery
system or companion diagnostic. Such products may be regulated as “combination products” in the U.S. and the EU, which are generally defined as
products consisting of components from two or more regulatory categories (e.g., drug/device, device/biologic, drug/biologic). In the U.S., each component of
a combination product is subject to the requirements established by the FDA for that type of component, whether a new drug, biologic or device. In order to
facilitate pre-market review of combination products, the FDA designates one of its centers to have primary jurisdiction for the pre-market review and
regulation of the overall product based upon a determination by the FDA of the primary mode of action of the combination product. The determination
whether a product is a combination product or two separately regulated products is made by the FDA on a case-by-case basis. In the EU, if a device
intended to administer a medicinal product is sold together with such medicinal product in such a way that they form a single integral product which is
intended exclusively for use in the given combination and which is not reusable, that single integral product is regulated as a medicinal product. In addition,
the relevant general safety and performance requirements established for medical devices by EU medical devices legislation apply to the device component
of such combination products. Our product candidates intended for use with separately regulated devices, or expanded indications that we may seek for our
products used with such devices, may not be approved or may be substantially delayed in receiving approval if the devices do not gain and/or maintain their
own regulatory approvals or clearances. Where approval of the drug or biologic product and device is sought under a single application, the increased
complexity of the review process may delay approval. The FDA review process and criteria are not well-established areas, which could also lead to delays in
the approval process. In addition, because these devices are provided by unaffiliated third-party companies, we are dependent on the sustained cooperation
and effort of those third-party companies both to obtain regulatory approval and to maintain their own regulatory compliance. Failure of third-party companies
to assist in the approval process or to maintain their own regulatory compliance could delay or prevent approval of our product candidates, or limit our ability
to sell a product once it is approved.
From time to time during the development and regulatory approval process for our products and product candidates, we engage in discussions with
the FDA, the EMA and other comparable international regulatory authorities regarding our development programs, including discussions about the regulatory
requirements for approval. As part of these discussions, we sometimes seek advice in the design of our clinical programs from various regulatory agencies
globally, but we do not always follow such guidance.
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This increases the chance of adverse regulatory actions, but we try to always provide appropriate scientific evidence to support approval. Moreover,
sometimes different regulatory agencies provide different or conflicting advice. While we attempt to harmonize the advice we receive from multiple regulatory
authorities, it is not always practical to do so. Also, we may choose not to harmonize conflicting advice when harmonization would significantly delay clinical
trial data or is otherwise inappropriate. If we are unable to effectively and efficiently resolve and comply with the inquiries and requests of the FDA, the EMA
and other comparable international regulatory authorities, the approval of our product candidates may be delayed and their value may be reduced.
Any product for which we have obtained regulatory approval, or for which we obtain approval in the future, is subject to, or will be
subject to, extensive ongoing regulatory requirements by the FDA, the EMA and other comparable international regulatory authorities, and if we
fail to comply with regulatory requirements or if we experience unanticipated problems with our products, we may be subject to penalties, we will
be unable to generate revenues from the sale of such products, our potential for generating positive cash flow will be diminished, and the capital
necessary to fund our operations will be increased.
ALDURAZYME, BRINEURA, KUVAN, NAGLAZYME and VIMIZIM have received regulatory approval to be commercially marketed and sold in the
U.S., the EU and certain other countries, PALYNZIQ has received regulatory approval to be commercially marketed in the U.S., the EU, and Australia.
VOXZOGO has received regulatory approval to be commercially marketed in the U.S., the EU, and Brazil. ROCTAVIAN has received conditional approval to
be commercially marketed in the EU. Any product for which we have obtained regulatory approval, or for which we obtain regulatory approval in the future,
along with the manufacturing processes and practices, post-approval clinical research, product labeling, advertising and promotional activities for such
product, are subject to continual requirements of, and review by, the FDA, the EMA and/or other comparable international and national regulatory authorities.
These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, current good
manufacturing practices (cGMP) requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and
documents, import and export requirements and record keeping.
An example of the ongoing regulatory requirements our products are subject to is the PALYNZIQ Risk Evaluation and Mitigation Strategy (REMS)
program. In the U.S., PALYNZIQ is only available through the REMS program, which is required by the FDA to mitigate the risk of anaphylaxis while using
the product. Notable requirements of our REMS program include the following:
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prescribers must be certified by enrolling in the REMS program and completing training;
prescribers must prescribe auto-injectable epinephrine with PALYNZIQ;
pharmacies must be certified with the REMS program and must dispense PALYNZIQ only to patients who are authorized to receive it;
patients must enroll in the REMS program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the
risks and benefits of treatment with PALYNZIQ; and
patients must have auto-injectable epinephrine available at all times while taking PALYNZIQ.
Failure of prescribers, pharmacies or patients to enroll in our REMS program or to successfully complete and comply with its requirements may
result in regulatory action from the FDA or decreased sales of PALYNZIQ. The restrictions and requirements under our REMS program, as well as potential
changes to these restrictions and requirements in the future, subject us to increased risks and uncertainties, any of which could harm our business. The
requirement for a REMS program can materially affect the potential market for and profitability of a drug. We cannot predict whether the FDA will request,
seek to require or ultimately require modifications to, or impose additional requirements on, the PALYNZIQ REMS program, or whether the FDA will permit
modifications to the PALYNZIQ REMS program that we consider warranted. Any modifications required or rejected by the FDA could make it more difficult or
expensive for us to distribute PALYNZIQ in the U.S., impair the safety profile of PALYNZIQ, disrupt continuity of care for PALYNZIQ patients and/or
negatively affect sales of PALYNZIQ.
Moreover, promotional communications with respect to prescription drugs, including biologics, are subject to a variety of legal and regulatory
restrictions and must be consistent with the information in the product’s approved labeling. In particular, a product may not be promoted for uses that are not
approved by the FDA or the EC as reflected in the product’s approved labeling. Although the FDA and other comparable international and national regulatory
authorities do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional
communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued. The FDA
and other national competent authorities or international regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label
uses, and a company that is found to have improperly promoted off-label uses may be subject to significant civil, criminal and administrative penalties. Thus,
we are not able to promote any products we develop for indications or uses for which they are not approved. Additionally, in the EU, it is prohibited to
promote prescription drugs to the general public and we are therefore limited to promote our products exclusively to healthcare professionals.
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Moreover, if original FDA approval for one of our product candidates is granted via the accelerated approval pathway, we will be required to conduct
a post-marketing confirmatory trial to verify and describe the clinical benefit in support of full approval. An unsuccessful post-marketing study or failure to
complete such a study with due diligence could result in the withdrawal of the FDA’s marketing approval for a product candidate. For example, VOXZOGO is
approved in the U.S. under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in confirmatory studies. To fulfill this post-marketing requirement, we intend to use our ongoing
open-label extension studies compared to available natural history. In addition, the FDA and the EC often require post-marketing testing and surveillance to
monitor the effects of products. The FDA, the EMA and other comparable international regulatory agencies may condition approval of our product candidates
on the completion of such post-marketing clinical studies. These post-marketing studies may suggest that a product causes undesirable side effects or may
present a risk to the patient.
Discovery after approval of previously unknown problems with any of our products, manufacturers or manufacturing processes, or failure to comply
with regulatory requirements, may result in actions such as:
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restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials;
restrictions on product manufacturing processes;
restrictions on the marketing of a product;
restrictions on product distribution;
requirements to conduct post-marketing clinical trials;
untitled or warning letters or other adverse publicity;
withdrawal of the products from the market;
refusal to approve pending applications or supplements to approved applications that we submit;
recall of products;
refusal to permit the import or export of our products;
product seizure;
fines, restitution or disgorgement of profits or revenue;
injunctions; or
imposition of civil or criminal penalties.
If such regulatory actions are taken, our value and our operating results will be adversely affected. Additionally, if the FDA, the EMA or any other
comparable international regulatory authorities withdraws its approval of a product, we will be unable to generate revenues from the sale of that product in
the relevant jurisdiction, our potential for generating positive cash flow will be diminished and the capital necessary to fund our operations will be increased.
Accordingly, we continue to expend significant time, money and effort in all areas of regulatory compliance, including manufacturing, production, product
surveillance, post-marketing studies and quality control.
To obtain regulatory approval to market our products, preclinical studies and costly and lengthy clinical trials are required and the
results of the studies and trials are highly uncertain. Likewise, preliminary, initial or interim data from clinical trials should be considered
carefully and with caution because the final data may be materially different from the preliminary, initial or interim data, particularly as more
patient data become available.
As part of the drug development process we must conduct, at our own expense, preclinical studies in the laboratory, including studies in animals,
and clinical trials on humans for each product candidate. The number of preclinical studies and clinical trials that regulatory authorities require varies
depending on the product candidate, the disease or condition the drug is being developed to address and regulations applicable to the particular drug.
Generally, new drugs for diseases or conditions that affect larger patient populations, are less severe, or are treatable by alternative strategies must be
validated through additional preclinical and clinical trials and/or clinical trials with higher enrollments. With respect to our early-stage product candidates, we
may need to perform multiple preclinical studies using various doses and formulations before we can begin clinical trials, which could result in delays to our
development timeline. Furthermore, even if we obtain favorable results in preclinical studies, the results in humans may be significantly different. After we
have conducted preclinical studies, we must demonstrate that our product candidates are safe and efficacious for use in the targeted human patients in
order to receive regulatory approval for commercial sale. Clinical testing is expensive and can take many years to complete, and its outcome is inherently
uncertain. Failure can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of our product candidates
may not be
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predictive of the results of later-stage clinical trials, and favorable data from interim analyses do not ensure the final results of a trial will be favorable. From
time to time, we have and may in the future publish or report preliminary, initial or interim data from our clinical trials. Preliminary, initial or interim data from
our clinical trials may not be indicative of the final results of the trial and are subject to the risk that one or more of the clinical outcomes may materially
change as patient enrollment continues and/or more patient data become available. In this regard, such data may show initial evidence of clinical benefit, but
as patients continue to be followed and more patient data become available, there is a risk that any therapeutic effects will not be durable in patients and/or
will decrease over time or cease entirely. Preliminary, initial or interim data also remain subject to audit and verification procedures that may result in the final
data being materially different from such preliminary, initial or interim data. As a result, preliminary, initial or interim data should be considered carefully and
with caution until the final data are available.
Product candidates may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical
trials, or despite having favorable data in connection with an interim analysis. A number of companies in the biopharmaceutical industry have suffered
significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Also, as
noted above, we do not always follow the advice of regulatory authorities or comply with all of their requests regarding the design of our clinical programs. In
those cases, we may choose a development program that is inconsistent with the advice of regulatory authorities, which may limit the jurisdictions where we
conduct clinical trials and/or adversely affect our ability to obtain approval in those jurisdictions where we do not follow the regulatory advice.
Adverse or inconclusive clinical results could stop us from obtaining regulatory approval of our product candidates. Additional factors that can cause
delay or termination of our clinical trials include:
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slow or insufficient patient enrollment;
slow recruitment of, and completion of necessary institutional approvals at, clinical sites;
budgetary constraints or prohibitively high clinical trial costs;
longer treatment time required to demonstrate efficacy;
lack of sufficient supplies of the product candidate;
adverse medical events or side effects in treated patients, including immune reactions;
lack of effectiveness of the product candidate being tested;
availability of competitive therapies to treat the same indication as our product candidates;
regulatory requests for additional clinical trials or preclinical studies;
deviations in standards for Good Clinical Practice (GCP); and
disputes with or disruptions in our relationships with clinical trial partners, including CROs, clinical laboratories, clinical sites, and principal
investigators.
Government price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our current and
future products, which would adversely affect our revenues and results of operations.
We expect that coverage and reimbursement may be increasingly restricted in all the markets in which we sell our products. The escalating cost of
healthcare has led to increased pressure on the healthcare industry to reduce costs. In particular, drug pricing by pharmaceutical companies has been under
scrutiny for many years and continues to be subject to intense political and public debate in the U.S. and abroad. Governmental and private third-party
payers have proposed healthcare reforms and cost reductions. A number of federal and state proposals to control the cost of healthcare, including the cost
of drug treatments, have been made in the U.S. Specifically, there have been several recent U.S. congressional inquiries and proposed bills and enacted
legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient
programs, and reform government program reimbursement methodologies for drugs. Further, Congress and the executive branch have each indicated that
they will continue to seek new legislative and/or administrative measures to control drug costs. In some international markets, the government controls the
pricing, which can affect the profitability of drugs. Current government regulations and possible future legislation regarding healthcare may affect coverage
and reimbursement for medical treatment by third-party payers, which may render our products not commercially viable or may adversely affect our future
revenues and gross margins.
International operations are also generally subject to extensive price and market regulations, and there are many proposals for additional cost-
containment measures, including proposals that would directly or indirectly impose additional price controls or mandatory price cuts or reduce the value of
our intellectual property portfolio. As part of these cost containment
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measures, some countries have imposed and continue to propose revenue caps limiting the annual volume of sales of our products. Some of these caps are
significantly below the actual demand in certain countries, and if the trend regarding revenue caps continues, our future revenues and gross margins may be
adversely affected. For example, in the EU, governments influence the price of medicinal products through their pricing and reimbursement rules and control
of national healthcare systems that fund a large part of the cost of those products to consumers. EU Member States are free to restrict the range of
medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.
Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed to
by the government. An EU Member State may approve a specific price for the medicinal product, or it may instead adopt a system of direct or indirect
controls on the profitability of the company placing the medicinal product on the market, including volume-based arrangements, caps and reference pricing
mechanisms. Other EU Member States allow companies to fix their own prices for medicines but monitor and control company profits. The downward
pressure on healthcare costs in general, particularly prescription medicines, has become very intense. Pharmaceutical products may face competition from
lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products.
Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication or cost-effective by third-
party payers. There is also no assurance that an adequate level of reimbursement will be established even if coverage is available or that the third-party
payers’ reimbursement policies will not adversely affect our business.
We cannot predict the extent to which our business may be affected by these or other potential future legislative or regulatory developments.
However, future price controls or other changes in pricing regulation or negative publicity related to our product pricing or the pricing of pharmaceutical drugs
generally could restrict the amount that we are able to charge for our current and future products or our sales volume, which would adversely affect our
revenues and results of operations.
Government healthcare reform could increase our costs and adversely affect our revenues and results of operations.
Our industry is highly regulated and changes in law may adversely impact our business, operations or financial results. In the U.S., there have been
and continue to be a number of legislative initiatives to contain healthcare costs. In the U.S., there have been several recent congressional inquiries,
proposed and enacted federal and state legislation and executive action designed to, among other things, bring more transparency to drug pricing, review
the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program
reimbursement methodologies for drug products. Any reduction in reimbursement from Medicare and other government programs may result in a similar
reduction in payments from private payers. Recently, healthcare reform initiatives culminated in the enactment of the Inflation Reduction Act (IRA) in August
2022, which will, among other things, allow U.S. Department of Health and Human Services (HHS) to negotiate the selling price of certain drugs and
biologics that the CMS reimburses under Medicare Part B and Part D, although only high-expenditure single-source drugs that have been approved for at
least 7 years (11 years for biologics) can be selected by CMS for negotiation. The IRA permits the Secretary of HHS to implement many of these provisions
through guidance, as opposed to regulation, for the initial years. Manufacturers that fail to comply with the IRA may be subject to various penalties, including
civil monetary penalties.
Prior to the IRA, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010
(collectively, the PPACA) is a sweeping measure intended to, among other things, expand healthcare coverage within the U.S., primarily through the
imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program. Several provisions of the law have affected
us and increased certain of our costs. Since its enactment, there have been executive, judicial and congressional challenges to certain aspects of the
PPACA. Although the PPACA has generally been upheld thus far, it is unclear how continued challenges to the law may impact the PPACA and our
business. In addition, other legislative changes have been adopted since the PPACA was enacted. Some of these changes have resulted in additional
reductions in Medicare and other healthcare funding, which could have a material adverse effect on our customers and, accordingly, our financial operations.
In addition, individual states in the U.S. have also increasingly passed legislation and implemented regulations designed to control pharmaceutical
product pricing, including price or patient reimbursement constraints, price disclosure and reporting requirements, discounts, restrictions on certain product
access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk
purchasing. Moreover, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical
products and which suppliers will be included in their prescription drug and other healthcare programs.
Likewise, in many EU Member States, legislators and other policymakers continue to propose and implement healthcare cost-containing measures
in response to the increased attention being paid to healthcare costs in the EU. Certain of these changes could impose limitations on the prices we will be
able to charge for our products and any approved product candidates or the amounts of reimbursement available for these products from governmental and
private third-party payers, may increase the tax obligations on pharmaceutical companies or may facilitate the introduction of generic competition with
respect to our products. Further, an increasing number of EU Member States and other non-U.S. countries use prices for medicinal products established in
other countries as “reference prices” to help determine the price of the product in their own territory. If the price of one of our
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products decreases substantially in a reference price country, it could impact the price for that product in other countries. Consequently, a downward trend in
prices of our products in some countries could contribute to similar downward trends elsewhere, which would have a material adverse effect on our revenues
and results of operations. Moreover, in order to obtain reimbursement for our products in some countries, we may be required to conduct clinical trials that
compare the cost-effectiveness of our products to other available therapies.
We anticipate that the IRA, PPACA and other healthcare reform measures that may be adopted in the future in the U.S. or abroad, may result in
more rigorous coverage criteria and an additional downward pressure on the reimbursement our customers may receive for our products. Recently there has
been heightened governmental scrutiny in countries worldwide over the manner in which manufacturers set prices for their marketed products. Legally
mandated price controls on payment amounts by governmental and private third-party payers or other restrictions could harm our business, results of
operations, financial condition and prospects. The implementation of cost containment measures or other healthcare reforms may prevent us from being able
to generate revenue, attain profitability or commercialize our products.
If we fail to obtain or maintain orphan drug exclusivity for some of our products, our competitors may obtain approval to sell the same
drugs to treat the same conditions and our revenues will be reduced.
As part of our business strategy, we have developed and may in the future develop some drugs that may be eligible for FDA and EU orphan drug
designation. Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is intended to treat a rare disease or condition, defined as
a patient population of fewer than 200,000 in the U.S. In the EU, pursuant to the Orphan Regulation, orphan drug designation is available if a sponsor can
establish that: (1) the medicine is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no
more than five in 10,000 people in the EU at the time the application is made, or, (2) that it is intended for the diagnosis, prevention or treatment of a life-
threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives derived from the orphan status, it is unlikely that the
marketing of the medicine in the EU would generate sufficient return to justify the necessary investment. In both cases, the applicant must demonstrate that
there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if such method
exists, the medicine will be of significant benefit to those affected by that condition.
In the U.S., the company that first obtains FDA approval for a designated orphan drug for a given rare disease receives marketing exclusivity for
use of that drug for the stated condition for a period of seven years. Orphan drug exclusive marketing rights may be lost if the FDA later determines that the
request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug. In addition, the FDA may approve
another drug during a period of orphan drug exclusivity if the second drug is found to be clinically superior to the first drug. In the EU, a ten-year period of
market exclusivity (extendable to twelve years for orphan drugs that have complied with an agreed Pediatric Investigation Plan (PIP) pursuant to Regulation
1901/2006), during which similar medicines for the same indication cannot be placed on the market, is granted. MAs may also be granted to a similar
medicinal product with the same orphan indication if: (i) the applicant can establish that the second medicinal product, although similar to the orphan
medicinal product already authorized is safer, more effective or otherwise clinically superior to the orphan medicinal product already authorized; (ii) the MA
holder for the first orphan medicinal product grants its consent; or (iii) if the MA holder of the orphan medicinal product is unable to supply sufficient
quantities. The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it can be demonstrated on the basis of
available evidence that the criteria for its designation as an orphan medicine are no longer satisfied, for example if the original orphan medicinal product has
become sufficiently profitable not to justify maintenance of market exclusivity. Because the extent and scope of patent protection for some of our products is
limited, orphan drug designation is especially important for our products that are eligible for orphan drug designation. For eligible products, we plan to rely on
the exclusivity period under the Orphan Drug Act and/or the Orphan Regulation, as applicable, to maintain a competitive position. If we do not obtain orphan
drug exclusivity for our products that do not have broad patent protection, our competitors may then sell the same drug to treat the same condition and our
revenues will be reduced.
Even though we have obtained orphan drug designation for certain of our product candidates and even if we obtain orphan drug designation for our
future product candidates, due to the uncertainties associated with developing biopharmaceutical products, we may not be the first to obtain marketing
approval for any particular orphan indication, which means that we may not obtain orphan drug exclusivity and could also potentially be blocked from
approval of certain product candidates until the competitor product’s orphan drug exclusivity period expires. Moreover, with respect to certain biologics and
gene therapies, there may be some uncertainty regarding how similarity between product candidates designed to treat the same rare disease or condition
may affect such product candidates’ orphan drug exclusivities. For biologics and gene therapies, the FDA’s determination of whether a drug is the same drug
or a different drug will be based on the principal molecular structural features of the products. For gene therapy products, the FDA has stated in guidance
that it generally intends to consider certain key features such as transgenes and vectors used in gene therapy products to be principal molecular structural
features. Further, even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because
different drugs can be approved for the same condition and the same drug can be approved for different conditions and potentially used off-label in the
orphan indication. Even after an orphan drug is approved and granted orphan drug exclusivity, the FDA can subsequently approve the same drug for the
same condition if the FDA concludes that the later drug is safer or more effective or
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makes a major contribution to patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug, nor gives the
drug any advantage in the regulatory review or approval process.
We may face competition from biosimilars approved through an abbreviated regulatory pathway.
Our ALDURAZYME, BRINEURA, NAGLAZYME, PALYNZIQ and VIMIZIM products are regulated by the FDA as biologics under the Federal Food,
Drug, and Cosmetic Act and the Public Health Service Act (the PHS Act). Biologics require the submission of a BLA and approval by the FDA prior to being
marketed in the U.S. The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created a regulatory pathway under the PHS Act for the
abbreviated approval of biological products that are demonstrated to be “biosimilar” or “interchangeable” with an FDA-approved biological product. A similar
abridged MA process is available to biosimilar products in the EU. In particular, applicants for MAs of biosimilars are required to demonstrate through
comprehensive comparability studies with the reference biological medicine that: a) their biological medicine is highly similar to the reference medicine,
notwithstanding natural variability inherent to all biological medicines; and b) there are no clinically meaningful differences between the biosimilar and the
reference medicine in terms of safety, quality and efficacy.
In the U.S., in order to meet the standard of interchangeability, a sponsor must demonstrate that the biosimilar product can be expected to produce
the same clinical result as the reference product, and for a product that is administered more than once, that the risk of switching between the reference
product and biosimilar product is not greater than the risk of maintaining the patient on the reference product. The BPCIA establishes a period of 12 years of
exclusivity for reference products. In the EU, a medicinal product containing a new active substance benefits from eight years of data exclusivity, during
which biosimilar applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market
exclusivity, during which such biosimilar products may not be placed on the market. The two-year period may be extended to three years if during the first
eight years a new therapeutic indication with significant clinical benefit over existing therapies is approved. Our products approved under BLAs in the U.S. or
as a result of Marketing Authorization Applications (MAAs) in the EU, as well as our product candidates that may be approved in the future, could be
reference products for biosimilar marketing applications.
Changes in funding for the FDA, the EMA, other comparable international regulatory authorities and other government agencies or
government shutdowns could hinder the ability of such agencies to hire and retain key leadership and other personnel or otherwise prevent
those agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.
Changes in funding levels of government agencies can affect their ability to hire and retain key personnel and carry out their normal functions that
support our business. For example, the ability of the FDA or the EMA to timely review and approve INDs or MAAs for our product candidates may be
hindered by a lack of resources and qualified personnel. In addition, funding of other government agencies on which our operations rely, including those that
fund research and development activities, is subject to the political budget process, which is inherently fluid and unpredictable.
Government shutdowns could also impact the ability of government agencies to function normally and support our operations. For example, the
U.S. federal government has shut down repeatedly since 1980, including for a period of 35 days beginning on December 22, 2018. During a shutdown,
certain regulatory agencies, such as the FDA, have had to furlough key personnel and stop critical activities. If a prolonged government shutdown occurs, it
could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our
business.
Risks Related to Our Gene Therapy Programs
Our gene therapy products and product candidates are based on a novel technology, which presents additional development,
manufacturing, regulatory and treatment risks in relation to our other, more traditional drug development programs.
In addition to the risks set forth in this Risk Factors section associated with more traditional pharmaceutical drugs, there are additional, unique
development, manufacturing, regulatory and treatment risks associated with gene therapy products and product candidates like ROCTAVIAN and BMN 331.
The goal of gene therapy is to be able to correct an inborn genetic defect through administration of therapeutic genetic material containing non-
defective gene copies. The gene copies are designed to reside permanently in a patient, allowing the patient to produce an essential protein or ribonucleic
acid (RNA) molecule that a healthy person would normally produce. There is a risk, however, that the new gene copies will produce too little or too much of
the desired protein or RNA. Although administration of a gene therapy product like ROCTAVIAN is intended to correct an inborn genetic defect for at least
several years, there is a risk that the therapeutic effect will not be durable and production of the desired protein or RNA will decrease more quickly or cease
entirely earlier than expected. If the therapeutic effect decreases significantly or ceases entirely, it is uncertain whether redosing is possible or would be
effective. Furthermore, because gene therapy treatment is irreversible, there may be challenges in managing side effects, particularly those caused by
potential overproduction of the desired protein. Adverse effects would not be able to be reversed or relieved by stopping dosing, and we may have to
develop additional clinical safety procedures. Additionally, because
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the new gene copies are designed to reside permanently in a patient, there is a risk that they will disrupt other normal biological molecules and processes,
including other healthy genes, and we may not learn the nature and magnitude of these side effects until long after clinical trials have been completed.
Moreover, gene therapy products are relatively novel and complex and have only in limited cases been manufactured at scales sufficient for pivotal
trials and commercialization. Few pharmaceutical contract manufacturers specialize in gene therapy products and those that do are still developing
appropriate processes and facilities for large-scale production. We invested a considerable amount of capital building our own commercial gene therapy
manufacturing facility, which may be subject to significant impairment if our gene therapy programs are unsuccessful. As we develop, seek to optimize and
operate the gene therapy manufacturing process, we will likely face technical and scientific challenges, considerable capital costs, and potential difficulty in
recruiting and hiring experienced, qualified personnel. There may also be unexpected technical or operational issues during clinical or commercial
manufacturing campaigns. As a result, we could experience manufacturing delays that prevent us from completing our clinical studies in a timely manner, if
at all, or commercializing our gene therapy products on a profitable basis, if at all.
Furthermore, we may experience regulatory challenges specific to gene therapy that cause significant delays or unanticipated costs, or that cannot
be solved. Although numerous companies are currently advancing gene therapy product candidates through clinical trials, the FDA has only approved a very
small number of vector-based gene therapy products thus far. Moreover, there are very few approved gene therapy products outside the U.S. As a result, it
is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for our gene therapy product candidates in any jurisdiction.
Regulatory requirements governing gene and cell therapy products are still evolving and may continue to change in the future. For example, in October
2020, it was reported that the Director of the Center for Biologics Evaluation and Research, the center of the FDA responsible for reviewing marketing
applications for gene therapies, stated that the FDA will assess the importance of durability of effect differently for a gene therapy that treats a disease that
has no other available therapies versus a condition for which there are multiple approved treatments. Additionally, in September 2021, the FDA held a
Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) to discuss toxicity risks of adeno-associated virus (AAV) vectors for gene therapy and
to seek the CTGTAC’s insight into strategies to evaluate and mitigate risks in the context of AAV vector-based product design and quality, preclinical studies,
and clinical trials. ROCTAVIAN and BMN 331 are AAV vector-based product candidates. Further, the FDA continues to develop and publish new guidance
and policies, such as the publication of four draft or final gene therapy-specific guidance documents in 2022. These guidance documents and other recent
policy statements demonstrate that the FDA’s regulatory requirements for gene therapies are likely to continue to evolve based upon factors such as the
intended disease or class of diseases, product type or mechanism of action, as well as broader considerations such as the kinds of evidence that will be
required for gene therapy products to take advantage of expedited development programs. Delay or failure to obtain, or unexpected costs in obtaining, the
regulatory approval necessary to bring our gene therapy product candidates to market could have a negative effect on our business and financial condition.
As compared to our other, more traditional products, gene therapy products may present additional problems with respect to the pricing,
coverage, and reimbursement and acceptance of the product.
In addition to the risks set forth in this Risk Factors section associated with commercializing more traditional pharmaceutical drugs, there are
additional, unique commercial risks associated with gene therapy products like ROCTAVIAN. Due to the relative novelty of gene therapy and the potential to
provide extended duration therapeutic treatment with a one-time administration, we face uncertainty with respect to the pricing, coverage and reimbursement
of these products. In order to recover our research and development costs and commercialize one-time treatments on a profitable basis, the cost of a single
administration of ROCTAVIAN is substantial, and it is likely other gene therapy products would also require relatively high prices. Therefore, coverage and
reimbursement by governments and other third-party payers is essential for the vast majority of patients to be able to afford ROCTAVIAN or other gene
therapy products that we may commercialize in the future. Accordingly, sales of our gene therapy products will depend substantially on the extent to which its
cost will be paid by third-party payers. Even if coverage is provided, the reimbursement amounts approved by third-party payers may not be high enough to
allow us to realize sufficient revenues from our investment in the development of our gene therapy products.
With respect to ROCTAVIAN specifically, we have entered into, and plan to enter into additional, outcomes-based agreements for the product with
third-party payers to assist with realizing the value and sharing the risk of a one-time treatment, which make us subject to potential repayments if a patient
does not respond to therapy or the therapeutic effect of the drug falls below specified thresholds. Although we will record reserves for potential refunds under
the outcomes-based agreements for ROCTAVIAN in the same period as sales, our revenues and financial results could be adversely affected if our
assumptions underlying our refund reserves differ from actual experience or otherwise underestimate refund obligations. Additionally, the increased
complexity of reimbursement with outcomes-based arrangements heightens the risk that our price reporting may be inaccurate or delayed, which may result
in fines and liability.
We also face uncertainty as to whether gene therapy will gain the acceptance of the public or the medical community. The commercial success of
ROCTAVIAN or any other gene therapy product candidate that may be approved in the future will depend, in part, on the acceptance of physicians, patients
and third-party payers of gene therapy products in general, and our product in particular, as medically necessary, cost-effective and safe. In particular, our
success will depend upon physicians prescribing our
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product in lieu of existing treatments they are already familiar with and for which greater clinical data may be available. Moreover, physicians and patients
may delay acceptance of one of our gene therapy treatments until the product has been on the market for a certain amount of time. Negative public opinion
or more restrictive government regulations could have a negative effect on our business and financial condition and may delay or impair the successful
commercialization of, and demand for, ROCTAVIAN or future gene therapy products.
We have implemented data access plans for our main clinical trials of ROCTAVIAN, which restrict our management’s review of emerging
key efficacy data from these trials. Without access to this ongoing data, management does not have the ability to adjust the trials based on such
emerging data, which could adversely impact the ultimate outcome of these trials.
In order to preserve the scientific integrity of our main ROCTAVIAN clinical trials and to allow us to only report on data at intervals that we believe
will be meaningful to investors, we have implemented data access plans related to these ongoing open-label trials, which plans are designed to significantly
mirror blinded trials. Pursuant to the plans, the ongoing emerging data for key endpoints are generally not accessed by us, with the exception that certain
specific data points are reviewed by a small group of medical personnel monitoring and managing the trials, and then, only to the extent necessary to allow
them to perform their monitoring responsibilities. As we disclose and publicly discuss prior data from one of these trials, such discussions do not incorporate
any of the currently emerging data that are being collected and reviewed by personnel monitoring the trial and, accordingly, this prior data may differ
significantly from more recent data that are only available to such personnel. Further, because our management does not have access to any of the ongoing
key efficacy data and does not have the ability to adjust the trials based on such emerging data, the data access plans could adversely impact the ultimate
outcome of the trials.
Financial and Financing Risks
If we incur operating losses or are unable to sustain positive cash flows for a period longer than anticipated, we may be unable to
continue our operations at planned levels and may be forced to reduce our operations.
Since we began operations in March 1997, we have been engaged in substantial research and development and capital investments, and we have
operated at a net loss for each year since our inception, with the exceptions of 2008, 2010, 2020 and 2022. Our future profitability and cash flows depend on
our marketing and selling of our products, the receipt of regulatory approval of our product candidates, our ability to successfully manufacture and market
any products, either by ourselves or jointly with others, our spending on our development programs, the impact of any possible future business development
transactions and other risks set forth in this Risk Factors section. The extent of our future losses and the timing of profitability and positive cash flows are
highly uncertain. If we fail to become profitable or are unable to sustain profitability and positive cash flows on a continuing basis, then we may be unable to
continue our operations at planned levels and be forced to reduce our operations.
If we fail to obtain the capital necessary to fund our operations, our financial results and financial condition will be adversely affected
and we will have to delay or terminate some or all of our product development programs.
As of December 31, 2022, we had cash, cash equivalents and investments totaling $1.6 billion and debt obligations of $1.1 billion (undiscounted),
which consisted of our 0.599% senior subordinated convertible notes due in 2024 (the 2024 Notes) and our 1.25% senior subordinated convertible notes due
in 2027 (the 2027 Notes). The 2024 Notes and the 2027 Notes (collectively, the Notes), if not converted, will be required to be repaid in cash at maturity in
August 2024 and May 2027, respectively. We will need cash not only to pay the ongoing interest due on the Notes during their term, but also to repay the
principal amount of the Notes if not converted.
We may require additional financing to fund the repayment of the Notes, future milestone payments and our future operations, including the
commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and
acquisitions. We may be unable to raise additional financing due to a variety of factors, including our financial condition, the status of our product programs,
and the general condition of the financial markets. If we fail to raise any necessary additional financing we may have to delay or terminate some or all of our
product development programs and our financial condition and operating results will be adversely affected.
We expect to continue to spend substantial amounts of capital for our operations for the foreseeable future. The amount of capital we will need
depends on many factors, including:
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our ability to successfully market and sell our products;
the time and cost necessary to develop commercial manufacturing processes, including quality systems, and to build or acquire manufacturing
capabilities;
the progress and success of our preclinical studies and clinical trials (including studies and the manufacture of materials);
the timing, number, size and scope of our preclinical studies and clinical trials;
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the time and cost necessary to obtain regulatory approvals and the costs of post-marketing studies which may be required by regulatory authorities;
the progress of research programs carried out by us;
any changes made to, or new developments in, our existing collaborative, licensing and other commercial relationships or any new collaborative,
licensing and other commercial relationships that we may establish;
Sanofi’s ability to continue to successfully commercialize ALDURAZYME; and
whether our convertible debt is converted to common stock in the future.
Moreover, our fixed expenses such as rent, license payments, interest expense and other contractual commitments are substantial and may
increase in the future. These fixed expenses may increase because we may enter into:
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additional licenses and collaborative agreements;
additional contracts for product manufacturing; and
additional financing facilities or arrangements.
We will need to raise additional funds from equity or debt securities, loans or collaborative agreements if we are unable to satisfy our liquidity
requirements. The sale of additional equity and/or equity-linked securities will result in additional dilution to our stockholders. Furthermore, additional
financing may not be available in amounts or on terms satisfactory to us or at all. This could result in the delay, reduction or termination of our research,
which could harm our business.
We have incurred substantial indebtedness that may decrease our business flexibility, access to capital, and/or increase our borrowing
costs, which may adversely affect our operations and financial results.
As of December 31, 2022, we had $1.1 billion (undiscounted) principal amount of indebtedness, including $495.0 million (undiscounted) principal
amount of indebtedness under the 2024 Notes and $600.0 million (undiscounted) principal amount of indebtedness under the 2027 Notes. In October 2018,
we entered into an unsecured credit agreement (the 2018 Credit Agreement) with Bank of America, N.A., as the administrative agent, swingline lender and a
lender, Citibank, N.A. as letter of credit issuer and each of Merrill Lynch, Pierce, Fenner & Smith Incorporated, Citibank, N.A. and Wells Fargo Securities,
LLC as joint lead arrangers and joint bookrunners, providing up to $200.0 million in revolving loan commitments (the 2018 Credit Facility). In May 2021, we
amended the 2018 Credit Facility to, among other things, extend the maturity date of the 2018 Credit Facility from October 19, 2021 to May 28, 2024. Our
indebtedness may:
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limit our ability to borrow additional funds for working capital, capital expenditures, acquisitions or other general business purposes;
limit our ability to use our cash flow or obtain additional financing for future working capital, capital expenditures, acquisitions or other general
business purposes;
require us to use a substantial portion of our cash flow from operations to make debt service payments;
limit our flexibility to plan for, or react to, changes in our business and industry;
place us at a competitive disadvantage compared to our less leveraged competitors; and
increase our vulnerability to the impact of adverse economic and industry conditions.
In addition, the 2018 Credit Facility contains, and any future indebtedness that we may incur may contain, financial and other restrictive covenants
that limit our ability to operate our business, raise capital or make payments under our other indebtedness. If we fail to comply with these covenants or to
make payments under our indebtedness when due, then we would be in default under that indebtedness, which could, in turn, result in that and our other
indebtedness becoming immediately payable in full. If we default under the 2018 Credit Facility, the outstanding borrowings thereunder could become
immediately due and payable, the 2018 Credit Facility lenders could refuse to permit additional borrowings under the facility, or it could lead to defaults under
agreements governing our current or future indebtedness, including the indentures governing the Notes. If we default under any series of the Notes, such
series of Notes could become immediately due and payable and it could lead to defaults under the other series of Notes and/or the 2018 Credit Facility.
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In addition, our ability to refinance our indebtedness will depend on the capital markets and our financial condition at such time.
Our outstanding indebtedness consists primarily of the 2024 Notes and 2027 Notes, which, if not converted, will be required to be repaid in cash at
maturity in August 2024 and May 2027, respectively. While we could seek to obtain additional third-party financing to pay for any amounts due in cash upon
maturity of the Notes, we cannot be sure that such third-party financing will be available on commercially reasonable terms, if at all.
In addition, we also may borrow up to $200.0 million in revolving loans under the 2018 Credit Facility, which would be required to be repaid in cash
at maturity on May 28, 2024.
Manufacturing Risks
If we fail to comply with manufacturing regulations, our financial results and financial condition will be adversely affected.
Before we can begin commercial manufacture of our products, regulatory authorities must approve marketing applications that identify authorized
manufacturing facilities operated by us or our contract manufacturers that have passed regulatory inspection and manufacturing processes that are
acceptable to the regulatory authorities. In addition, our pharmaceutical manufacturing facilities are continuously subject to scheduled and unannounced
inspection by the FDA, and other comparable EU and other national and international regulatory authorities, before and after product approval, to monitor
and ensure compliance with cGMP and other regulations. Our manufacturing facility in the U.S. has received a good manufacturing practice certificate from
the EMA for the manufacture and distribution of ROCTAVIAN in the EU, been approved by the FDA and the EC for the manufacture of PALYNZIQ, and been
approved by the FDA, the EC, and health agencies in other countries for the manufacture of ALDURAZYME, BRINEURA, NAGLAZYME, VIMIZIM and
VOXZOGO. Our manufacturing facility in Shanbally, Cork, Ireland has been approved by the FDA, the EC, and health agencies in other countries for the
manufacture of VIMIZIM and BRINEURA. In addition, our third-party manufacturers’ facilities involved with the manufacture of our products have also been
inspected and approved by various regulatory authorities. Although we are not involved in the day-to-day operations of our contract manufacturers, we are
ultimately responsible for ensuring that our products are manufactured in accordance with cGMP regulations.
Due to the complexity of the processes used to manufacture our products and product candidates, we may be unable to continue to pass or initially
pass federal or international regulatory inspections in a cost-effective manner. For the same reason, any potential third-party manufacturer of our products or
our product candidates may be unable to comply with cGMP regulations in a cost-effective manner and may be unable to initially or continue to pass a
federal or international regulatory inspection.
If we, or third-party manufacturers with whom we contract, are unable to comply with manufacturing regulations, we may be subject to delay of
approval of our product candidates, warning or untitled letters, fines, unanticipated compliance expenses, recall or seizure of our products, total or partial
suspension of production and/or enforcement actions, including injunctions, and criminal or civil prosecution. These possible sanctions would adversely
affect our financial results and financial condition.
If we are unable to successfully develop and maintain manufacturing processes for our product candidates to produce sufficient
quantities at acceptable costs, we may be unable to support a clinical trial or be forced to terminate a program, or if we are unable to produce
sufficient quantities of our products at acceptable costs, we may be unable to meet commercial demand, lose potential revenue, have reduced
margins or be forced to terminate a program.
Due to the complexity of manufacturing our product candidates and products, we may not be able to manufacture sufficient quantities. Our inability
to produce enough of our product candidate at acceptable costs may result in the delay or termination of development programs. With respect to our
commercial portfolio, we may not be able to manufacture our products successfully with a commercially viable process or at a scale large enough to support
their respective commercial markets or at acceptable margins.
The development of commercially viable manufacturing processes typically is very difficult to achieve and is often very expensive and may require
extended periods of time. Changes in manufacturing processes (including manufacturing cell lines), equipment or facilities (including moving manufacturing
from one of our facilities to another one of our facilities or a third-party facility, or from a third-party facility to one of our facilities) may require us to complete
clinical trials to receive regulatory approval of any manufacturing modifications.
Also, we may be required to demonstrate product comparability between a biological product made after a manufacturing change and the product
made before implementation of the change through additional types of analytical and functional testing or may have to complete additional clinical studies. If
we contract for manufacturing services with an unproven process, our contractor is subject to the same uncertainties, high standards and regulatory controls,
and may therefore experience difficulty if further process development is necessary.
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Even a developed manufacturing process can encounter difficulties. Problems may arise during manufacturing for a variety of reasons, including
human error, mechanical breakdowns, problems with raw materials and cell banks, malfunctions of internal information technology systems, and other
events that cannot always be prevented or anticipated. Many of the processes include biological systems, which add significant complexity, as compared to
chemical synthesis. We expect that, from time to time, consistent with biotechnology industry expectations, certain production lots will fail to produce product
that meets our quality control release acceptance criteria. To date, our historical failure rates for all of our product programs have been within our
expectations, which are based on industry norms. If the failure rate increased substantially, we could experience increased costs, lost revenue, damage to
customer relations, time and expense investigating the cause and, depending upon the cause, similar losses with respect to other lots or products. If
problems are not discovered before the product is released to the market, recall and product liability costs may also be incurred.
In order to produce product within our time and cost parameters, we must continue to produce product within our expected success rate and yield
expectations. Because of the complexity of our manufacturing processes, it may be difficult or impossible for us to determine the cause of any particular lot
failure and we must effectively take corrective action in response to any failure in a timely manner.
We currently rely on third parties for portions of the manufacture of each of our products. If those manufacturers are unwilling or unable to fulfill their
contractual obligations or satisfy demand outside of or in excess of the contractual obligations, we may be unable to meet demand for these products or sell
these products at all and we may lose potential revenue. Further, the availability of suitable contract manufacturing capacity at scheduled or optimum times
is not certain.
In addition, our manufacturing processes subject us to a variety of federal, state and local laws and regulations governing the use, generation,
manufacture, storage, handling and disposal of hazardous materials and wastes resulting from their use. We incur significant costs in complying with these
laws and regulations.
Supply interruptions may disrupt our inventory levels and the availability of our products and product candidates and cause delays in
obtaining regulatory approval for our product candidates, or harm our business by reducing our revenues.
We depend on single-source suppliers for critical raw materials and a limited number of manufacturing facilities to manufacture our finished
products and product candidates. Numerous factors could cause interruptions in the supply or manufacture of our products and product candidates,
including:
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timing, scheduling and prioritization of production by our contract manufacturers or a breach of our agreements by our contract manufacturers;
labor interruptions;
changes in our sources for manufacturing;
the timing and delivery of shipments;
our failure to locate and obtain replacement suppliers and manufacturers as needed on a timely basis; and
conditions affecting the cost and availability of raw materials, including inflation.
If one of our suppliers or manufacturers fails or refuses to supply us with necessary raw materials or finished products or product candidates on a
timely basis or at all, it would take a significant amount of time and expense to qualify a new supplier or manufacturer. We may not be able to obtain active
ingredients or finished products from new suppliers or manufacturers on acceptable terms and at reasonable prices, or at all.
Any interruption in the supply of finished products could hinder our ability to distribute finished products to meet commercial demand and adversely
affect our financial results and financial condition.
With respect to our product candidates, production of product is necessary to perform clinical trials and successful registration batches are
necessary to file for approval to commercially market and sell product candidates. Delays in obtaining clinical material or registration batches could adversely
impact our clinical trials and delay regulatory approval for our product candidates.
If our Manufacturing, Marketing and Sales Agreement with Sanofi were terminated, we could be prevented from continuing to
commercialize ALDURAZYME or our ability to successfully commercialize ALDURAZYME would be delayed or diminished.
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Either party may terminate the Manufacturing, Marketing and Sales Agreement (the MMS Agreement) between Sanofi and us related to
ALDURAZYME for specified reasons, including if the other party is in material breach of the MMS Agreement, has experienced a change of control, as such
term is defined in the MMS Agreement, or has declared bankruptcy and also is in breach of the MMS Agreement. Although we are not currently in breach of
the MMS Agreement, there is a risk that either party could breach the MMS Agreement in the future. Either party may also terminate the MMS Agreement
upon one-year prior written notice for any reason.
If the MMS Agreement is terminated for breach, the breaching party will transfer its interest in the BioMarin/Genzyme LLC to the non-breaching
party, and the non-breaching party will pay a specified buyout amount for the breaching party’s interest in ALDURAZYME and in the BioMarin/Genzyme LLC.
If we are the breaching party, we would lose our rights to ALDURAZYME and the related intellectual property and regulatory approvals. If the MMS
Agreement is terminated without cause, the non-terminating party would have the option, exercisable for one year, to buy out the terminating party’s interest
in ALDURAZYME and in the BioMarin/Genzyme LLC at a specified buyout amount. If such option is not exercised, all rights to ALDURAZYME will be sold
and the BioMarin/Genzyme LLC will be dissolved. In the event of termination of the buyout option without exercise by the non-terminating party as described
above, all right and title to ALDURAZYME is to be sold to the highest bidder, with the proceeds to be split between Sanofi and us in accordance with our
percentage interest in the BioMarin/Genzyme LLC.
If the MMS Agreement is terminated by either party because the other party declared bankruptcy, the terminating party would be obligated to buy
out the other party and would obtain all rights to ALDURAZYME exclusively. If the MMS Agreement is terminated by a party because the other party
experienced a change of control, the terminating party shall notify the other party, the offeree, of its intent to buy out the offeree’s interest in ALDURAZYME
and the BioMarin/Genzyme LLC for a stated amount set by the terminating party at its discretion. The offeree must then either accept this offer or agree to
buy the terminating party’s interest in ALDURAZYME and the BioMarin/Genzyme LLC on those same terms. The party who buys out the other party would
then have exclusive worldwide rights to ALDURAZYME. The Amended and Restated Collaboration Agreement between us and Sanofi will automatically
terminate upon the effective date of the termination of the MMS Agreement and may not be terminated independently from the MMS Agreement.
If we were obligated or given the option to buy out Sanofi’s interest in ALDURAZYME and the BioMarin/Genzyme LLC, and thereby gain exclusive
rights to ALDURAZYME, we may not have sufficient funds to do so and we may not be able to obtain the financing to do so. If we fail to buy out Sanofi’s
interest, we may be held in breach of the agreement and may lose any claim to the rights to ALDURAZYME and the related intellectual property and
regulatory approvals. We would then effectively be prohibited from developing and commercializing ALDURAZYME. If this happened, not only would our
product revenues decrease, but our share price would also decline.
Risks Related to International Operations
We conduct a significant amount of our sales and operations outside of the U.S., which subjects us to additional business risks that
could adversely affect our revenues and results of operations.
A significant portion of the sales of our products are generated from countries other than the U.S., and we expect international markets will continue
to be important for the sales of any products approved in the future. We have operations in Canada and in several European, Middle Eastern, Asian, and
Latin American countries. We expect that we will continue to expand our international operations in the future. International operations inherently subject us
to a number of risks and uncertainties, including:
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the increased complexity and costs inherent in managing international operations;
diverse regulatory and compliance requirements, and changes in those requirements that could restrict our ability to manufacture, market and sell
our products;
political and economic instability, such as the instability caused by Russia’s invasion of Ukraine;
diminished protection of intellectual property in some countries outside of the U.S.;
trade protection measures and import or export licensing requirements;
difficulty in staffing and managing international operations;
differing labor regulations and business practices;
potentially negative consequences from changes in or interpretations of tax laws;
changes in international medical reimbursement policies and programs;
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financial risks such as longer payment cycles, difficulty collecting accounts receivable, exposure to fluctuations in foreign currency exchange rates
and potential currency controls imposed by non-U.S. governments;
regulatory and compliance risks that relate to maintaining accurate information and control over sales and distributors’ and service providers’
activities that may fall within the purview of the Foreign Corrupt Practices Act (the FCPA); and
rapidly evolving global laws and regulations relating to data protection and the privacy and security of commercial and personal information.
Any of these factors may, individually or as a group, have a material adverse effect on our business and results of operations. For example,
Russia’s invasion of Ukraine and the related impacts to Ukraine’s infrastructure and healthcare system has significantly impacted our ability to provide our
therapies to patients in Ukraine. Sanctions issued by the U.S. and other countries against Russia and Belarus in response to the attack on Ukraine and
related counter-sanctions issued by Russia have made it very difficult for us to operate in Russia and may have a material adverse impact on our ability to
sell our products and/or collect receivables from customers in Russia and Belarus.
As we continue to expand our existing international operations, we may encounter new risks. For example, as we focus on building our international
sales and distribution networks in new geographic regions, we must continue to develop relationships with qualified local distributors and trading companies.
If we are not successful in developing and maintaining these relationships, we may not be able to grow sales in these geographic regions. These or other
similar risks could adversely affect our revenues and profitability.
A significant portion of our international sales are made based on special access programs, and changes to these programs could
adversely affect our product sales and revenues in these countries.
We make a significant portion of our initial international sales of newly launched products through early access, special access or “named patient
sales” programs in markets where we are not required to obtain regulatory approval. For example, a significant portion of our international sales of
VOXZOGO since the product’s launch have been made through such programs. The specifics of the programs vary from country to country. Generally,
special approval must be obtained to initiate such programs, and in some cases, special approval must be obtained for each patient. The approval normally
requires an application or a lawsuit accompanied by evidence of medical need.
These programs are not well defined in some countries and are subject to changes in requirements, funding levels, unmet medical need and
classification of the disease treated by our product. Any change to these programs could adversely affect our ability to sell our products in those countries
and delay sales. If the programs are not funded by the respective government, there could be insufficient funds to pay for all patients. Further, governments
have and may continue to undertake unofficial measures to limit purchases of our products, including initially denying coverage for purchasers, delaying
orders, requiring additional in-country testing and denying or taking excessively long to approve customs clearance. Any such actions could materially delay
or reduce our revenues from such countries.
Without the special access programs, we would need to seek full product approval or official reimbursement to commercially market and sell our
products in certain jurisdictions. This can be an expensive and time-consuming process and may subject our products to additional price controls. Because
the number of patients is so small in some countries, it may not be economically feasible to seek, obtain and maintain a full product approval or official
reimbursement, and therefore the sales in such country would be permanently reduced or eliminated. For all of these reasons, if the special access
programs that we are currently using are eliminated or restricted, our revenues could be adversely affected.
Our international operations pose currency risks, which may adversely affect our operating results and net income.
A significant and growing portion of our revenues and earnings, as well as our substantial international net assets, are exposed to changes in
foreign exchange rates. As we operate in multiple foreign currencies, including the Euro, the Brazilian Real, the Canadian Dollar, the Colombian Peso, the
Argentine Peso and several other currencies, changes in those currencies relative to the U.S. Dollar (USD) will impact our revenues and expenses. If the
USD were to weaken against another currency, assuming all other variables remained constant, our revenues would increase, having a positive impact on
earnings, and our overall expenses would increase, having a negative impact on earnings. Conversely, if the USD were to strengthen against another
currency (as was the case for many currencies in 2022), assuming all other variables remained constant, our revenues would decrease, having a negative
impact on earnings, and our overall expenses would decrease, having a positive impact on earnings. In addition, because our financial statements are
reported in USD, changes in currency exchange rates between the USD and other currencies have had, and will continue to have, an impact on our results
of operations. Therefore, significant changes in foreign exchange rates can impact our results and our financial guidance.
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We implement currency hedges intended to reduce our exposure to changes in certain foreign currency exchange rates. However, our hedging
strategies may not be successful, and any of our unhedged foreign exchange exposures will continue to be subject to market fluctuations. These risks could
cause a material adverse effect on our business, financial position and results of operations and could cause the market value of our common stock to
decline.
U.S. export control and economic sanctions may adversely affect our business, financial condition and operating results. Moreover,
compliance with such regulatory requirements may increase our costs and negatively impact our ability to sell our products and collect cash
from customers.
Our products are subject to U.S. export control laws and regulations, including the U.S. Export Administration Regulations and various economic
and trade sanctions regulations administered by the U.S. Treasury Department’s Office of Foreign Assets Control (OFAC). Exports of our products and
solutions must be made in compliance with these laws and regulations. Changes to these laws and regulations, or to the countries, governments, persons or
activities targeted by such laws, could result in decreased use of our products, or hinder our ability to export or sell our products to existing or potential
customers, which would likely adversely affect our results of operations, financial condition or strategic objectives. For example, sanctions issued by the U.S.
and other jurisdictions against Russia and Belarus in response to the invasion of Ukraine have made it very difficult for us to operate in Russia and may have
a material adverse impact on our ability to sell our products and/or collect receivables from customers in Russia and Belarus. Moreover, if we fail to comply
with these laws and regulations, we could be subject to substantial civil or criminal penalties, including the possible loss of export or import privileges and
fines.
We rely on a general license from OFAC to sell our medicines for eventual use by hospital and clinic end-users in Iran. The use of this OFAC
general license requires us to observe strict conditions with respect to products sold, end-user limitations and payment requirements. Although we believe
we have maintained compliance with the general license requirements, there can be no assurance that the general license will not be revoked, the general
license will be renewed in the future or we will remain in compliance with the general license. A violation of the OFAC general license could result in
substantial fines, sanctions, civil or criminal penalties, competitive or reputational harm, litigation or regulatory action and other consequences that might
adversely affect our results of operations, financial condition or strategic objectives.
Moreover, U.S. export control and economic sanctions may make operating in certain countries more difficult and expensive. For example, we may
be unable to find distributors or financial institutions willing to facilitate the sale of our products and collection of cash from such sales in a cost-effective
manner, if at all.
Failure to comply with applicable anti-corruption legislation could result in fines, criminal penalties and materially adversely affect our
business, financial condition and results of operations.
We are required to comply with anti-corruption and anti-bribery laws in the jurisdictions in which we operate, including the FCPA in the U.S. and
other similar laws in other countries in which we do business. We operate in a number of countries that are recognized to have a reputation for corruption
and pose an increased risk of corrupt practices. We also regularly interact with government regulators in many countries, including those that are considered
higher risk for corruption, in order to secure regulatory approval to manufacture and distribute our products. The anti-corruption and anti-bribery laws to
which we are subject generally prohibit companies and their intermediaries from making improper payments to non-U.S. government officials or other
persons for the purposes of influencing official decisions or obtaining or retaining business and/or other benefits. These laws also require us to make and
keep books and records that accurately and fairly reflect our transactions and to devise and maintain an adequate system of internal accounting controls. As
part of our business, we deal with state-owned business enterprises, the employees and representatives of which may be considered non-U.S. government
officials for purposes of applicable anti-corruption laws.
Although we have adopted policies and procedures designed to ensure that we, our employees and third-party agents will comply with such laws,
there can be no assurance that such policies or procedures will work effectively at all times or protect us against liability under these or other laws for actions
taken by our employees, partners and other third parties with respect to our business. If we are not in compliance with anti-corruption laws and other laws
governing the conduct of business with government entities and/or officials (including local laws), we may be subject to criminal and civil penalties and other
remedial measures, which could harm our business, financial condition, results of operations, cash flows and prospects. Investigations of any actual or
alleged violations of such laws or policies related to us could harm our business, financial condition, results of operations, cash flows and prospects.
Moreover, there has been enhanced scrutiny of company-sponsored patient assistance programs, including insurance premium and co-pay
assistance programs and donations to third-party independent charities that provide such assistance. There has also been enhanced scrutiny by
governments on reimbursement support offerings, clinical education programs and promotional speaker programs. If we, our third-party agents or donation
recipients are deemed to have failed to comply with laws, regulations or government guidance in any of these areas, we could be subject to criminal or civil
sanctions. Any similar violations by our competitors could also negatively impact our industry reputation and increase scrutiny over our business and our
products.
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We face credit risks from government-owned or sponsored customers outside of the U.S. that may adversely affect our results of
operations.
Our product sales to government-owned or supported customers in various countries outside of the U.S. are subject to significant payment delays
due to government funding and reimbursement practices. This has resulted and may continue to result in an increase in days sales outstanding due to the
average length of time that we have accounts receivable outstanding. If significant changes were to occur in the reimbursement practices of these
governments or if government funding becomes unavailable, we may not be able to collect on amounts due to us from these customers and our results of
operations would be adversely affected.
Intellectual Property Risks
If we are unable to protect our intellectual property, we may not be able to compete effectively or preserve our market shares.
Where appropriate, we seek patent protection for certain aspects of our technology. Patent protection may not be available for some of the products
we are developing. If we must spend significant time and money protecting or enforcing our patents, designing around patents held by others or licensing,
potentially for large fees, patents or other proprietary rights held by others, our business and financial prospects may be harmed.
The patent positions of biopharmaceutical products are complex and uncertain. The scope and extent of patent protection for some of our products
and product candidates are particularly uncertain because key information on some of our product candidates has existed in the public domain for many
years. The composition and genetic sequences of animal and/or human versions of ALDURAZYME, NAGLAZYME and many of our product candidates have
been published and are believed to be in the public domain. The chemical structure of 6R-BH4 (the active ingredient in KUVAN) has also been published.
Publication of this information may prevent us from obtaining or enforcing patents relating to our products and product candidates, including without limitation
composition-of-matter patents, which are generally believed to offer the strongest patent protection.
We own or have licensed patents and patent applications related to our products. However, these patents and patent applications do not ensure the
protection of our intellectual property for a number of reasons, including without limitation the following:
• With respect to pending patent applications, unless and until actually issued, the protective value of these applications is impossible to determine.
We do not know whether our patent applications will result in issued patents.
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Patents have limited duration and expire.
Enforcing patents is expensive and may absorb significant time of our management. Management would spend less time and resources on
developing products, which could increase our operating expenses and delay product programs
Receipt of a patent may not provide much, if any, practical protection. For example, if we receive a patent with a narrow scope, then it will be easier
for competitors to design products that do not infringe on our patent.
The Leahy-Smith America Invents Act of 2011, which reformed certain patent laws in the U.S., may create additional uncertainty. Among the
significant changes are switching from a “first-to-invent” system to a “first-to-file” system, and the implementation of new procedures that permit
competitors to challenge our patents in the U.S. Patent and Trademark Office after grant.
It is also unclear whether our trade secrets are adequately protected. Our current and former employees, consultants or contractors may
unintentionally or willfully disclose trade secrets to competitors. Enforcing a claim that someone else illegally obtained and is using our trade secrets, as with
patent litigation, is expensive and time consuming, requires significant resources and has an unpredictable outcome. In addition, courts outside of the U.S.
are sometimes less willing to protect trade secrets. Furthermore, our competitors may independently develop equivalent knowledge, methods and know-how,
in which case we would not be able to enforce our trade secret rights against such competitors.
In the EU, materials we submit to the EMA in connection with our clinical trials that were traditionally regarded as confidential, proprietary
information, such as study protocols, information regarding manufacturing methods and controls, and intermediate data analyses, are now subject to public
disclosure. Moreover, clinical trial data submitted to the EMA in our MAAs are also available to the public. We are only permitted to redact from public
disclosures commercially confidential information, a standard which is construed narrowly and subject to the interpretation and final decision of the EU
regulatory authorities. EU regulations have resulted and will continue to result in the EMA’s public disclosure of certain of our proprietary information related
to recently completed and future clinical trials and MAA submissions. The move toward public disclosure of such development
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information could adversely affect our business in many ways, including, for example, resulting in the disclosure of our confidential methodologies for
development of our products, preventing us from obtaining intellectual property right protection for innovations, requiring us to allocate significant resources
to prevent other companies from violating our intellectual property rights, adding even more complexity to processing health data from clinical trials
consistent with applicable data privacy regulations, increasing scrutiny of our product candidates and products, and enabling competitors to use our clinical
trial information and data to gain approvals for their own products.
Competitors may interfere with our patent process in a variety of ways. Competitors may claim that they invented the claimed invention prior to us
or that they filed their application for a patent on a claimed invention before we did. Competitors may also claim that we are infringing on their patents and
therefore we cannot practice our technology. Competitors may also contest our patents by showing the patent examiner or a court that the invention was not
original, was not novel or was obvious, for example. In litigation, a competitor could claim that our issued patents are not valid or are unenforceable for a
number of reasons. If a court agrees, we would not be able to enforce that patent. Moreover, generic manufacturers may use litigation and regulatory means
to obtain approval for generic versions of our products notwithstanding our filed patents or patent applications.
If we are unable to protect our intellectual property, third parties could develop competing products, which could adversely affect our revenues and
financial results generally.
Competitors and other third parties may have developed intellectual property that could limit our ability to market and commercialize our
products and product candidates, if approved.
Similar to us, competitors continually seek intellectual property protection for their technology. Several of our development programs, such as
ROCTAVIAN, focus on therapeutic areas that have been the subject of extensive research and development by third parties for many years. Due to the
amount of intellectual property in our field of technology, we cannot be certain that we do not infringe intellectual property rights of competitors or that we will
not infringe intellectual property rights of competitors granted or created in the future. For example, if a patent holder believes our product infringes its patent,
the patent holder may sue us even if we have received patent protection for our technology. If someone else claims we infringe their intellectual property, we
would face a number of issues, including the following:
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Defending a lawsuit takes significant executive resources and can be very expensive.
If a court decides that our product infringes a competitor’s intellectual property, we may have to pay substantial damages.
• With respect to patents, in addition to requiring us to pay substantial damages, a court may prohibit us from making, selling, offering to sell,
importing or using our product unless the patent holder licenses the patent to us. The patent holder is not required to grant us a license. If a license
is available, it may not be available on commercially reasonable terms. For example, we may have to pay substantial royalties or grant cross
licenses to our patents and patent applications.
• We may need to redesign our product so it does not infringe the intellectual property rights of others.
•
Redesigning our product so it does not infringe the intellectual property rights of competitors may not be possible or could require substantial funds
and time.
We may also support and collaborate in research conducted by government organizations, hospitals, universities or other educational institutions.
These research partners may be unwilling to grant us any exclusive rights to technology or products derived from these collaborations.
If we do not obtain required licenses or rights, we could encounter delays in our product development efforts while we attempt to design around
other patents or may be prohibited from making, using, importing, offering to sell or selling products requiring these licenses or rights. There is also a risk
that disputes may arise as to the rights to technology or products developed in collaboration with other parties. If we are not able to resolve such disputes
and obtain the licenses or rights we need, we may not be able to develop or market our products.
Risks Related to Ownership of Our Securities
Our stock price has been and may in the future be volatile, and an investment in our stock could suffer a decline in value.
Our stock price has been and may in the future be volatile. Our valuation and stock price may have no meaningful relationship to current or
historical earnings, asset values, book value or many other criteria based on conventional measures of stock value. The market price of our common stock
will fluctuate due to factors including:
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product sales and profitability of our products;
• manufacturing, supply or distribution of our product candidates and products;
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progress of our product candidates through the regulatory process and our ability to successfully commercialize any such products that receive
regulatory approval;
results of clinical trials, announcements of technological innovations or new products by us or our competitors;
generic competition to KUVAN tablets and powder described above in this Risk Factors section or potential generic competition from future
competitors;
government regulatory action affecting our product candidates, our products or our competitors’ product candidates and products in both the U.S.
and non-U.S. countries;
developments or disputes concerning patent or proprietary rights;
general market conditions and fluctuations for the emerging growth and pharmaceutical market sectors;
economic conditions in the U.S. or abroad;
negative publicity about us or the pharmaceutical industry;
changes in the structure of healthcare payment systems;
cybersecurity incidents experienced by us or others in our industry;
broad market fluctuations in the U.S., the EU or in other parts of the world;
actual or anticipated fluctuations in our operating results, including due to timing of large periodic orders for our products by governments in certain
countries;
changes in company assessments or financial estimates by securities analysts;
acquisitions of products, businesses, or other assets; and
sales of our shares of stock by us, our significant stockholders, or members of our management or Board of Directors.
Furthermore, the stock markets have recently experienced extreme price and volume fluctuations that have affected and continue to affect the
market prices of equity securities of many companies. In some cases, these fluctuations have been unrelated or disproportionate to the operating
performance of those companies. In the past, companies that have experienced volatility in the market price of their stock have been subject to securities
class action litigation. For example, in September 2020, after a substantial drop in our stock price that followed an announcement providing a regulatory
update regarding ROCTAVIAN, we and certain of our officers were sued in a putative class action lawsuit alleging violations of the federal securities laws for
allegedly making materially false or misleading statements. In addition, in October 2021, after a drop in our stock price that followed an announcement
providing a regulatory update regarding BMN 307, we and certain of our current and former officers were sued in a putative class action lawsuit alleging
violations of the federal securities laws for allegedly making materially false or misleading statements. We may be the target of additional litigation of this
type in the future as well. Securities litigation against us could result in substantial costs and divert our management’s time and attention from other business
concerns, which could harm our business.
In addition, our stock price can be materially adversely affected by factors beyond our control, such as disruptions in global financial markets or
negative trends in the biotechnology sector of the economy, even if our business is operating well.
Conversion of the Notes will dilute the ownership interest of existing stockholders, including holders who had previously converted their
Notes, or may otherwise depress the price of our common stock.
The conversion of some or all of the Notes will dilute the ownership interests of existing stockholders. Any sales in the public market of the common
stock issuable upon such conversion could adversely affect prevailing market prices of our common stock. In addition, the existence of the Notes may
encourage short selling by market participants because the conversion of the Notes could be used to satisfy short positions, or anticipated conversion of the
Notes into shares of our common stock could depress the price of our common stock.
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The fundamental change repurchase feature of the Notes may delay or prevent an otherwise beneficial attempt to take us over.
The terms of the Notes require us to offer to repurchase the Notes in the event of a fundamental change (as defined in each indenture governing
the Notes). A takeover of us would trigger options by the respective holders of the applicable Notes to require us to repurchase such Notes. This may have
the effect of delaying or preventing a takeover of us that would otherwise be beneficial to our stockholders or investors in the Notes.
Anti-takeover provisions in our charter documents and under Delaware law may make an acquisition of us, which may be beneficial to
our stockholders, more difficult.
We are incorporated in Delaware. Certain anti-takeover provisions of Delaware law and our charter documents as currently in effect may make a
change in control of us more difficult, even if a change in control would be beneficial to the stockholders. Our anti-takeover provisions include provisions in
our restated certificate of incorporation and amended and restated bylaws providing that stockholders’ meetings may only be called by our Chairman, the
lead independent director or the majority of our Board of Directors and that the stockholders may not take action by written consent and requiring that
stockholders that desire to nominate any person for election to our Board of Directors or to make any proposal with respect to business to be conducted at a
meeting of our stockholders be submitted in appropriate form to our Secretary within a specified period of time in advance of any such meeting. Additionally,
our Board of Directors has the authority to issue shares of preferred stock and to determine the terms of those shares of stock without any further action by
our stockholders. The rights of holders of our common stock are subject to the rights of the holders of any preferred stock that may be issued. The issuance
of preferred stock could make it more difficult for a third party to acquire a majority of our outstanding voting stock. Delaware law also prohibits corporations
from engaging in a business combination with any holders of 15% or more of their capital stock until the holder has held the stock for three years unless,
among other possibilities, our Board of Directors approves the transaction. Our Board of Directors may use these provisions to prevent changes in the
management and control of us. Also, under applicable Delaware law, our Board of Directors may adopt additional anti-takeover measures in the future.
Our amended and restated bylaws designate the Court of Chancery of the State of Delaware and the federal district courts of the U.S. as
the exclusive forums for the adjudication of certain disputes, which could limit our stockholders’ ability to obtain a favorable judicial forum for
disputes with us or our directors, officers, or employees.
Our amended and restated bylaws provide that the Court of Chancery of the State of Delaware is the sole and exclusive forum for the following
types of actions or proceedings under Delaware statutory or common law:
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any derivative claim or cause of action brought on our behalf;
any claim or cause of action for breach of a fiduciary duty owed by any director, officer or other employee of BioMarin to us or our stockholders;
any claim or cause of action against us or any of our directors, officers or other employees arising pursuant to any provision of the General
Corporation Law of the State of Delaware, our restated certificate of incorporation or our amended and restated bylaws; any claim or cause of
action seeking to interpret, apply, enforce or determine the validity of our restated certificate of incorporation or our amended and restated bylaws;
any claim or cause of action as to which the General Corporation Law of the State of Delaware confers jurisdiction to the Court of Chancery of the
State of Delaware; and
any claim or cause of action against us or any of our directors, officers or other employees that is governed by the internal affairs doctrine.
This exclusive-forum provision would not apply to suits brought to enforce a duty or liability created by the Securities Act of 1933, as amended, the
Exchange Act or any other claim for which the U.S. federal courts have exclusive jurisdiction. In addition, our amended and restated bylaws provide that the
federal district courts of the U.S. of America will be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities
Act.
While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a
claim in a venue other than those designated in the exclusive forum provisions. In such instance, we would expect to vigorously assert the validity and
enforceability of the exclusive forum provisions of our amended and restated bylaws. This may require significant additional costs associated with resolving
such action in other jurisdictions and there can be no assurance that the provisions will be enforced by a court in those other jurisdictions.
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These exclusive forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our
directors, officers, or other employees, which may discourage lawsuits against us and our directors, officers, and other employees. If a court were to find
either of our exclusive forum provisions to be inapplicable or unenforceable in an action, we may incur further significant additional costs associated with
resolving the dispute in other jurisdictions, all of which could seriously harm our business. Our amended and restated bylaws further provide that any person
or entity that acquires any interest in shares of our capital stock will be deemed to have notice of and consented to the provisions of such provisions.
We depend upon our key personnel and our ability to attract and retain qualified employees.
General Risk Factors
Our future growth and success will depend in large part on our continued ability to attract, retain, manage and motivate our employees. The loss of
the services of a significant portion of our workforce or any member of our senior management or the inability to hire or retain qualified personnel could
adversely affect our ability to execute our business plan and harm our operating results.
Because of the specialized nature of our business, we rely heavily on our ability to attract and retain qualified scientific, technical and managerial
personnel. In particular, the loss of one or more of our senior executive officers could be detrimental to us if we do not have an adequate succession plan or
if we cannot recruit suitable replacements in a timely manner. While our senior executive officers are parties to employment agreements with us, these
agreements do not guarantee that they will remain employed with us in the future. In addition, in many cases, these agreements do not restrict our senior
executive officers’ ability to compete with us after their employment is terminated.
The competition for qualified personnel in the pharmaceutical field is intense, and there is a limited pool of qualified potential employees to recruit.
This competition was exacerbated during the COVID-19 pandemic, and we have recently experienced increased employee turnover like many other
employers in the U.S. during the “great resignation.” Due to the intense competition for talent, we may be unable to continue to attract and retain qualified
personnel necessary for the development of our business or to recruit suitable replacement personnel. If we are unsuccessful in our recruitment and
retention efforts, our business may be harmed.
Our success depends on our ability to manage our growth.
Our two newest products, VOXZOGO and ROCTAVIAN, address potentially larger patient populations than most of our other products, and product
candidates that we are currently developing or may license or acquire in the future may be intended for similarly larger patient populations than we have
historically targeted. In order to continue development of such product candidates and marketing of products with larger markets, we will need to continue
expanding our operations. To manage expansion effectively, we need to continue to develop and improve our research and development capabilities,
manufacturing and quality capacities, sales and marketing capabilities, financial and administrative systems and standard processes for global operations.
Our staff, financial resources, systems, procedures or controls may be inadequate to support our operations and may increase our exposure to regulatory,
competitive, and corruption risks and our management may be unable to manage successfully current or future market opportunities or our relationships with
customers and other third parties.
New tax laws or regulations that are enacted or existing tax laws and regulations that are interpreted, modified or applied adversely to us
or our customers may have a material adverse effect on our business and financial condition.
New tax laws or regulations could be enacted at any time, and existing tax laws or regulations could be interpreted, modified or applied in a manner
that is adverse to us or our customers, which could adversely affect our business and financial condition. For example, the Tax Cuts and Jobs Act, the
Coronavirus Aid, Relief, and Economic Security Act and the Inflation Reduction Act enacted many significant changes to the U.S. tax laws. Future guidance
from the Internal Revenue Service and other tax authorities with respect to such legislation may affect us, and certain aspects of such legislation could be
repealed or modified in future legislation. In addition, it is uncertain if and to what extent various states will conform to federal tax laws. Any future tax
legislation could increase our U.S. tax expense and could have a material adverse impact on our business and financial condition.
Moreover, changes in the tax laws of jurisdictions in which we conduct business could arise, including as a result of the base erosion and profit
shifting (BEPS) project that is being led by the Organization for Economic Co-operation and Development (OECD), and other initiatives led by the OECD or
the EC. For example, the OECD, which represents a coalition of member countries including the U.S. and other countries in which we have operations, is
working on proposals, commonly referred to as “BEPS 2.0”, which, if implemented, would make important changes to the international tax system. These
proposals are based on two “pillars”, Pillar One focuses on the allocation of taxing rights in respect of certain profits of multinational enterprises with annual
global revenue above 20 billion euros and profitability above 10% to the jurisdictions within which they carry on business (based on the thresholds, we
currently expect to be outside the scope of the Pillar One proposals) and Pillar Two imposes a minimum effective tax rate of 15% on certain multinational
enterprises that have consolidated revenues of at least 750 million euros in at least two out of the last four years (based on the thresholds, we currently
expect that we could fall within the scope of the Pillar Two
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proposals). The EU has adopted a Council Directive requiring aspects of the Pillar Two proposal to be transposed into the national laws of EU Member
States by December 31, 2023, and a number of other countries in which we conduct business are also planning to enact such rules. The implementation of
such rules may increase the amount of tax we have to pay, increase tax uncertainty and may adversely affect our provision for income taxes, results of
operations and cash flows. It is not uncommon for taxing authorities in different countries to have conflicting views, for instance, with respect to, among other
things, the manner in which the arm’s length standard is applied for transfer pricing purposes, or with respect to the valuation of intellectual property. If tax
authorities successfully challenge our transfer prices as not reflecting arm’s length transactions, they could require us to adjust our transfer prices and
thereby reallocate our income to reflect these revised transfer prices, resulting in a higher tax liability. In addition, if a country from which income is
reallocated does not agree with the reallocation, both that country and the other country to which the income was allocated could tax the same income,
potentially resulting in double taxation. If tax authorities were to allocate income to a higher tax jurisdiction, subject our income to double taxation or assess
interest and penalties, it would increase our consolidated tax liability, which could adversely affect our business, financial condition, results of operations and
cash flows.
If we are found in violation of healthcare laws or privacy and data protection laws, we may be required to pay penalties, be subjected to
scrutiny by regulators or governmental entities, or be suspended from participation in government healthcare programs, which may adversely
affect our business, reputation, financial condition and results of operations.
We are subject to various healthcare laws and regulations in the U.S. and internationally, including anti-kickback laws, false claims laws, data
privacy and security laws, and laws related to ensuring compliance. In the U.S., the federal Anti-Kickback Statute makes it illegal for any person or entity,
including a pharmaceutical company, to knowingly and willfully offer, solicit, pay or receive any remuneration, directly or indirectly, in exchange for or to
induce the referral of business, including the purchase, order or prescription of a particular drug, for which payment may be made under federal healthcare
programs, such as Medicare and Medicaid. Under the federal Anti-Kickback Statute and related regulations, certain arrangements are deemed not to violate
the federal Anti-Kickback Statute if they fit within a statutory exception or regulatory safe harbor. However, the exceptions and safe harbors are drawn
narrowly, and practices that involve remuneration not intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do
not qualify for an exception or safe harbor. Our practices may not in all cases meet all of the criteria for safe harbor protection from Anti-Kickback liability,
although we seek to comply with these safe harbors. Many states have adopted laws similar to the federal Anti-Kickback Statute, some of which apply to
referral of patients for healthcare services reimbursed by any source, not just governmental payers.
Federal and state false claims laws, including the civil False Claims Act and the Civil Monetary Penalties Law, prohibit any person or entity from
knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false
statement to have a false claim paid, or knowingly making, using, or causing to be made or used, a false record or statement to avoid, decrease or conceal
an obligation to pay money to the federal government. In addition, certain marketing practices, including off-label promotion, may also violate false claims
laws.
Under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), we also are prohibited from, among other things, knowingly and
willfully executing a scheme to defraud any healthcare benefit program, including private payers, or knowingly and willfully falsifying, concealing or covering
up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items
or services.
In addition, recent healthcare reform legislation has strengthened these laws in the U.S. For example, the PPACA, among other things, amends the
intent requirement of the federal Anti-Kickback Statute and criminal healthcare fraud statutes. A person or entity no longer needs to have actual knowledge
of these statutes or specific intent to violate them in order to commit a violation. Moreover, the PPACA provides that the government may assert that a claim
including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False
Claims Act.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes
obligations, including mandatory contractual terms, on certain types of individuals and entities, with respect to safeguarding the privacy, integrity, availability,
security and transmission of individually identifiable health information. Many state and non-U.S. laws also govern the privacy and security of health
information. They often differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. The global
data protection landscape is rapidly evolving, and implementation standards and enforcement practices are likely to remain uncertain for the foreseeable
future. In the U.S., California enacted the California Consumer Privacy Act (CCPA), which took effect on January 1, 2020. The CCPA gives California
consumers expanded rights to access and delete their personal information, opt out of certain personal information sales, and receive detailed information
about how their personal information is used. The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that is
expected to increase data breach litigation. The CCPA was expanded substantially on January 1, 2023 when the California Privacy Rights Act of 2020
(CPRA) took effect and amended the CCPA. Following the CPRA amendments, the CCPA, among other things, give consumers the ability to limit use of
information deemed to be sensitive, increase the maximum penalties for violations concerning consumers under age 16, expands an individual’s private right
of action and establishes the California Privacy Protection Agency to implement and enforce the new law and impose administrative fines.
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In addition to California, other U.S. states have recently adopted consumer data protection and privacy laws, and more U.S. states may do so in the
future. This creates the potential for a patchwork of overlapping but different state laws and could mark the beginning of a trend toward more stringent
privacy legislation in the U.S., which could increase our potential liability and adversely affect our business, financial condition, and results of operations.
Many other states are considering proposed comprehensive data privacy legislation and all 50 states have passed some form of legislation relating to
privacy or cybersecurity.
Aspects of the CCPA, CPRA and similar laws in other states and their interpretation and enforcement remain uncertain. The potential effects of
these laws are far-reaching and may require us to modify our data processing practices and policies and to incur substantial costs and expenses in an effort
to comply. Complying with these or other similar laws, regulations, amendments to or re-interpretations of existing laws and regulations, and contractual or
other obligations relating to privacy, data protection, data transfers, data localization, or information security may require us to make changes to our services
to enable us or our customers to meet new legal requirements, incur substantial operational costs, modify our data practices and policies, and restrict our
business operations. Any actual or perceived failure by us to comply with these laws, regulations, or other obligations may lead to significant fines, penalties,
regulatory investigations, lawsuits, significant costs for remediation, damage to our reputation, or other liabilities.
The European Regulation 2016/679, known as the General Data Protection Regulation (GDPR), as well as EEA Member State legislations
supplementing such regulation, apply to the processing of personal data of individuals located in the EEA, including health-related information, by companies
located in the EEA, or in certain circumstances, by companies located outside of the EEA. These laws impose strict obligations on the ability to collect,
record, store, disclose, use and transmit personal data, including health-related information. These include several requirements relating to (i) obtaining, in
some situations, the informed consent of the individuals to whom the personal data relates, (ii) the information provided to the individuals about how their
personal information is used, (iii) ensuring the security and confidentiality of the personal data, (iv) the obligation to notify regulatory authorities and affected
individuals of personal data breaches, (v) extensive internal privacy governance obligations, and (vi) obligations to honor rights of individuals in relation to
their personal data (for example, the right to access, correct and delete their data). Switzerland has adopted similar restrictions.
The GDPR and other European data protection laws generally restrict the transfer of personal information from Europe, including the EEA and
Switzerland, to the U.S. and most other countries unless the parties to the transfer have implemented specific safeguards to protect the transferred personal
information. One of the primary safeguards allowing U.S. companies to import personal information from the EEA has been the EC’s Standard Contractual
Clauses (SCCs). However, the Court of Justice of the EU (CJEU) issued a decision that called into question whether the SCCs can lawfully be used for
transfers of personal information from Europe to the United States or most other countries. At present, there are few, if any, viable alternatives to the SCCs,
on which we have relied for personal information transfers from Europe to the United States and other “third countries.” After the mentioned CJEU judgment,
new sets of SCCs were published on June 4, 2021. Most importantly, the use of SCCs does not any longer automatically ensure compliance with the GDPR.
Instead, companies remain required to conduct a data transfer impact assessment for each transfer, which adds a compliance burden.
Potential pecuniary fines for noncompliance with the GDPR may be up to the greater of €20 million or 4% of annual global revenue. The GDPR has
increased our responsibility and liability in relation to personal data that we process and has increased our compliance costs. The EU regulations that make
certain materials we submit to the EMA in connection with our clinical trials subject to public disclosure have increased the risk that we may unintentionally
disclose personal information protected under the GDPR and thereby incur associated penalties and suffer reputational damage.
In addition to the U.S. and European countries, other countries in which we operate have also enacted data privacy laws or may do so in the future.
For example, Brazil’s General Data Protection Law (LGPD), which is modeled on the GDPR, took effect on August 16, 2020.
Substantial new laws and regulations affecting compliance have also been adopted in the U.S. and certain non-U.S. countries, which may require
us to modify our business practices with healthcare practitioners. For example, in the U.S., the PPACA, through the Physician Payments Sunshine Act,
requires certain drug, biologicals and medical supply manufacturers to collect and report to CMS information on payments or transfers of value to physicians
(defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physicians assistants and nurse
practitioners), and teaching hospitals, as well as investment and ownership interests held by such physicians and their immediate family members during the
preceding calendar year. In addition, there has been a recent trend of increased state regulation of payments made to physicians. Certain states and/or local
jurisdictions mandate implementation of compliance programs, compliance with the Office of Inspector General Compliance Program Guidance for
Pharmaceutical Manufacturers and the Pharmaceutical Research and Manufacturers of America (PhRMA) Code on Interactions with Healthcare
Professionals, the registration of pharmaceutical sales representatives and/or the tracking and reporting of gifts, compensation and other remuneration to
physicians, marketing expenditures, and drug pricing. Likewise, in many non-U.S. countries there is an increasing focus on the relationship between drug
companies and healthcare practitioners. Recently enacted non-U.S. legislation creates reporting obligations on payments, gifts and benefits made to these
professionals. The shifting regulatory environment and the need to implement systems to comply with multiple jurisdictions with different compliance and/or
reporting requirements increases the costs of maintaining compliance and the possibility that we may violate one or more of the requirements and be subject
to fines or sanctions.
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Due to the breadth of the healthcare and privacy and data protection laws described above, the narrowness of available statutory and regulatory
exceptions and safe harbors and the increased focus by law enforcement agencies in enforcing such laws, our business activities could be subject to
challenge under one or more of such laws. If we are found in violation of one of these laws, we may be subject to significant criminal, civil or administrative
sanctions, including damages, fines, disgorgement, imprisonment, contractual damages, reputational harm, diminished profits and future earnings, additional
reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance
with these laws, curtailment of our operations, and debarment, suspension or exclusion from participation in government healthcare programs, any of which
could adversely affect our business, financial condition and results of operations.
If product liability lawsuits are successfully brought against us, we may incur substantial liabilities.
We are exposed to the potential product liability risks inherent in the testing, manufacturing and marketing of human pharmaceuticals. We currently
maintain insurance against product liability lawsuits for the commercial sale of our products and for the clinical trials of our product candidates.
Pharmaceutical companies must balance the cost of insurance with the level of coverage based on estimates of potential liability. Historically, the potential
liability associated with product liability lawsuits for pharmaceutical products has been unpredictable. Although we believe that our current insurance is a
reasonable estimate of our potential liability and represents a commercially reasonable balancing of the level of coverage as compared to the cost of the
insurance, we may be subject to claims in connection with our clinical trials and commercial use of our products and product candidates for which our
insurance coverage may not be adequate and we may be unable to avoid significant liability if any product liability lawsuit is brought against us. If we are the
subject of a successful product liability claim that exceeds the limits of any insurance coverage we obtain, we may incur substantial charges that would
adversely affect our earnings and require the commitment of capital resources that might otherwise be available for the development and commercialization
of our product programs.
We rely significantly on information technology systems and any failure, inadequacy, interruption or security lapse of that technology,
including any cybersecurity incidents, could harm our ability to operate our business effectively and have a material adverse effect on our
business, reputation, financial condition, and results of operations.
We rely significantly on our information technology systems to effectively manage and maintain our operations, inventory and internal reports, to
manufacture and ship products to customers and to timely invoice them. Any failure, inadequacy or interruption of that infrastructure or security lapse
(whether intentional or inadvertent) of that technology, including cybersecurity incidents or attacks, could harm our ability to operate our business effectively.
Our ability to manage and maintain our operations, inventory and internal reports, to manufacture and ship our products to customers and timely invoice
them depends significantly on our enterprise resource planning, production management and other information systems. Our technology systems, including
our cloud technologies, continue to increase in multitude and complexity, making them potentially vulnerable to breakdown, cyberattack and other
disruptions. Potential problems and interruptions associated with the implementation of new or upgraded technology systems or with maintenance or
adequate support of existing systems could disrupt or reduce the efficiency of our operations and expose us to greater risk of security breaches.
Cybersecurity incidents resulting in the failure of our enterprise resource planning system, production management or other systems to operate effectively or
to integrate with other systems, or a breach in security or other unauthorized access or unavailability of these systems or those of any third parties in our
supply chain or on whom we otherwise depend, have occurred in the past and may affect our ability in the future to manage and maintain our operations,
inventory and internal reports, and result in delays in product fulfillment and reduced efficiency of our operations.
As part of our business, we collect, store, and transmit large amounts of confidential information, proprietary data, intellectual property, and
personal data. The information and data processed and stored in our technology systems, and those of our research collaborators, CROs, contract
manufacturers, suppliers, distributors, or other third parties on whom we depend to operate our business, may be vulnerable to loss, damage, denial-of-
service, unauthorized access or misappropriation. Data security breaches may be the result of unauthorized or unintended activity (or lack of activity) by our
employees, contractors, or others with authorized access to our network or malware, hacking, business email compromise, phishing, ransomware or other
cyberattacks directed by third parties. While we have implemented measures to protect our information and data stored in our technology systems and those
of the third parties that we rely on, our efforts may not be successful.
We have experienced and may continue to experience cybersecurity incidents, although to our knowledge we have not experienced any material
incident or interruption to date. If such a significant event were to occur, it could result in a material disruption of our development programs and commercial
operations, including due to a loss, corruption or unauthorized disclosure of our trade secrets, personal data or other proprietary or sensitive information.
Further, these cybersecurity incidents can lead to the public disclosure of personal information (including sensitive personal information) of our employees,
clinical trial patients and others and result in demands for ransom or other forms of blackmail. Such attacks, including phishing attacks and attempts to
misappropriate or compromise confidential or proprietary information or sabotage enterprise IT systems, are of ever-increasing levels of sophistication and
are made by groups and individuals with a wide range of motives (including industrial espionage) and expertise, including by organized criminal groups,
“hacktivists”, nation states and others. Moreover, the costs to us to investigate and mitigate cybersecurity incidents could be significant. For example, the
loss of clinical trial data could result in delays in our product development or regulatory approval efforts and significantly increase our costs to recover or
reproduce the data. Any security breach that results in the unauthorized access, use or disclosure of personal data may require us to notify individuals,
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governmental authorities, credit reporting agencies, or other parties pursuant to privacy and security laws and regulations or other obligations. Such a
security compromise could harm our reputation, erode confidence in our information security measures, and lead to regulatory scrutiny. To the extent that
any disruption or security breach resulted in a loss of, or damage to, our data or systems, or inappropriate disclosure of confidential, proprietary or personal
information, we could be exposed to a risk of loss, enforcement measures, penalties, fines, indemnification claims, litigation and potential civil or criminal
liability, which could materially adversely affect our business, financial condition and results of operations.
Not all our contracts contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are
sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations. We cannot be sure that our insurance
coverage will be adequate or sufficient to protect us from or to mitigate liabilities arising out of our privacy and security practices, that such coverage will
continue to be available on commercially reasonable terms or at all, or that such coverage will pay future claims.
If a natural disaster, terrorist or criminal activity or other unforeseen event caused significant damage to our facilities or those of our
third-party manufacturers and suppliers or significantly disrupted our operations or those of our third-party manufacturers and suppliers, we may
be unable to meet demand for our products and lose potential revenue, have reduced margins, or be forced to terminate a program.
The occurrence of an earthquake or other catastrophic disaster could cause damage to our facility and equipment, or that of our third-party
manufacturers or single-source suppliers, which could materially impair the ability for us or our third-party manufacturers to manufacture our products and
product candidates. Our Galli Drive facility, located in Novato, California, is currently our only manufacturing facility for ALDURAZYME, NAGLAZYME,
VOXZOGO and PALYNZIQ and is one of two manufacturing facilities for BRINEURA and VIMIZIM. Our gene therapy manufacturing facility is also located in
Novato, California, and it is currently our only manufacturing facility to support ROCTAVIAN clinical development activities, commercial demand for
ROCTAVIAN in the EU, and anticipated commercial demand for ROCTAVIAN to the extent it receives approval by the FDA or other regulatory authorities.
These facilities are located in the San Francisco Bay Area near known earthquake fault zones and are vulnerable to significant damage from earthquakes.
We, the third-party manufacturers with whom we contract and our single-source suppliers of raw materials, which include many of our critical raw materials,
are also vulnerable to damage from other types of disasters, including fires, explosions, floods, and similar events. If any disaster were to occur, or any
terrorist or criminal activity caused significant damage to our facilities or the facilities of our third-party manufacturers and suppliers, our ability to
manufacture our products, or to have our products manufactured, could be seriously, or potentially completely, impaired, and our commercialization efforts
and revenues could be seriously impaired.
Moreover, other unforeseen events, such as power outages, could significantly disrupt our operations or those of our third-party manufacturers and
suppliers, which could result in significant delays in the manufacture of our products and adversely impact our commercial operations and revenues. Pacific
Gas and Electric Company, the electric utility in the San Francisco Bay Area where many of our facilities are located, commenced widespread blackouts
during the fall of 2019 to avoid and contain wildfires sparked during strong wind events by downed power lines or equipment failures. While we have not
experienced damage to our facilities or material disruption to our operations as a result of these power outages, ongoing blackouts, particularly if prolonged
or frequent, could impact our business going forward. The insurance that we carry, the inventory that we maintain and our risk mitigation plans may not be
adequate to cover our losses resulting from disasters or other business interruptions.
Our business is affected by macroeconomic conditions.
Various macroeconomic factors could adversely affect our business and the results of our operations and financial condition, including changes in
inflation, interest rates, foreign currency exchange rates, natural disasters, lasting effects of the COVID-19 pandemic or other global public health threats and
overall economic conditions and uncertainties, including those resulting from the current and future conditions in the global financial markets and volatility
and disruptions in the equity and debt markets. For instance, COVID-19 previously adversely affected our ability to source materials and supplies. If inflation
(such as that recently observed in the U.S. and elsewhere) or other factors were to significantly increase our business costs, it may not be feasible to pass
price increases on to our customers due to the process by which healthcare providers are reimbursed for our products by the government. Interest rates, the
liquidity of the credit markets and the volatility of the capital markets could also affect the value of our investments and our ability to liquidate our investments
in order to fund our operations. We purchase or enter into a variety of financial instruments and transactions, including investments in commercial paper, the
extension of credit to corporations, institutions and governments and hedging contracts. If any of the issuers or counterparties to these instruments were to
default on their obligations, it could materially reduce the value of the transaction and adversely affect our cash flows.
We sell our products in countries that face economic volatility and weakness. Although we have historically collected receivables from customers in
those countries, sustained weakness or further deterioration of the local economies and currencies may cause customers in those countries to be unable to
pay for our products. Additionally, if one or more of these countries were unable to purchase our products, our revenues would be adversely affected.
Interest rates and the ability to access credit markets could also adversely affect the ability of our customers/distributors to purchase, pay for and
effectively distribute our products, which could limit our ability to obtain sufficient materials and supplies
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necessary for production of our therapies. Similarly, these macroeconomic factors could affect the ability of our contract manufacturers, sole-source or
single-source suppliers to remain in business or otherwise manufacture or supply product. Failure by any of them to remain a going concern could affect our
ability to manufacture products.
Additionally, the lasting effects of the COVID-19 pandemic could continue to adversely affect our business, results of our operations, and financial
condition. The COVID-19 pandemic impacted our global revenue sources and overall business operations by, for example, presenting challenges to our
ability to find adequate resources to staff clinical trials, impacting patients’ ability to participate in trials, affecting our ability to source materials and supplies
for trials and otherwise delaying trials, and the pandemic could continue to adversely impact our financial results and our business generally in 2023.
Ongoing and future effects of the COVID-19 pandemic (or any future pandemic or other global public health threat) on all aspects of our business and
operations and the duration of such effects are highly uncertain and difficult to predict. Moreover, while the long-term economic impact and the duration of
the COVID-19 pandemic may be difficult to predict, the pandemic has resulted in, and may continue to result in, significant disruption of global financial
markets, which could reduce our ability to access capital and could negatively affect our liquidity and the liquidity and stability of markets for our common
stock and Notes. In addition, a recession, further market correction or depression resulting from the COVID-19 pandemic or other global public health threat
could materially adversely affect our business and the value of our common stock and Notes.
To the extent macroeconomic conditions continue to adversely affect our business and financial results, they may also have the effect of
heightening many of the other risks described in this Risk Factors section, such as those relating to our conducting a significant amount of our sales and
operations outside of the U.S., exposure to changes in foreign exchange rates, our need to generate sufficient cash flows to service our indebtedness and
finance our operations and the volatility of our stock price.
54
Item 1B. Unresolved Staff Comments
None.
Item 2. Properties
The following table contains information about our significant owned and leased properties as of December 31, 2022:
Location
Approximate
Square Feet
Use
San Rafael facility, San Rafael, California
407,300 Corporate headquarters, laboratory and office
Several facilities in Novato, California
Several leased facilities in Novato, California
Clinical and commercial manufacturing, laboratory and
office
293,300
164,000 Office and warehouse
Shanbally facility, Cork, Ireland
260,700 Manufacturing, laboratory and office
Lease
Expiration
Date
Owned
property
Owned
property
2023
Owned
property
We expect that these properties, together with our other smaller leased office facilities in various countries, will be adequate for our operations for
the foreseeable future.
Item 3. Legal Proceedings
On September 25, 2020, a purported shareholder class action lawsuit was filed against us, our Chief Executive Officer, our President of Worldwide
Research and Development and our Chief Financial Officer in the United States District Court in the Northern District of California, alleging violations under
Sections 10(b) and 20(a) of the Securities Exchange Act of 1934 as amended (the Exchange Act). The complaint alleges that we made materially false or
misleading statements regarding the clinical trials and Biologics License Application (BLA) for ROCTAVIAN (formerly known as valoctocogene roxaparvovec)
by purportedly failing to disclose that differences between the Company’s Phase 1/2 and Phase 3 clinical studies limited the ability of the Phase 1/2 study to
support ROCTAVIAN’s durability of effect and, as a result, that it was foreseeable that the Food and Drug Administration (FDA) would not approve the BLA
without additional data. The complaint seeks an unspecified amount of damages, prejudgment and post-judgment interest, attorneys’ fees, expert fees, and
other costs. The lead plaintiff filed an amended complaint in February 2021, dropping our Chief Financial Officer as a defendant, and asserting that the
Company misled investors about the progress of the FDA's review of our BLA for ROCTAVIAN. On April 22, 2021, we moved to dismiss the amended
complaint. On January 6, 2022, the court denied our motion to dismiss. We answered the amended complaint on February 15, 2022. Plaintiff filed a motion
for class certification on October 17, 2022. We filed an opposition to Plaintiff’s motion for class certification on January 27, 2023. Trial is scheduled to begin
on May 20, 2024. We believe that the claims have no merit and we intend to vigorously defend this action.
On October 22, 2021, a purported securities class action lawsuit was filed against us, our Chief Executive Officer, our current and prior Chief
Financial Officers, and our President of Worldwide Research & Development in the United States District Court for the Northern District of California, alleging
violations under Sections 10(b) and 20(a) of the Exchange Act. The complaint alleges that we made materially false or misleading statements regarding
BMN 307 by purportedly failing to disclose information about BMN 307’s safety profile, and by purportedly overstating BMN 307’s clinical and commercial
prospects. The complaint seeks an unspecified amount of damages, pre-judgment and post-judgment interest, attorneys’ fees, expert fees, and other costs.
The Court appointed lead plaintiffs and lead counsel on January 10, 2022. Lead plaintiffs filed an amended complaint on March 25, 2022. We filed a motion
to dismiss the amended complaint on May 25, 2022. On January 19, 2023, the Court granted our motion to dismiss the complaint without prejudice. On
February 21, 2023, the court dismissed the complaint with prejudice at plaintiffs’ request. Plaintiffs filed a notice indicating that they plan to appeal the court’s
January 19, 2023 order. We believe that the claims have no merit and we intend to vigorously defend this action.
On January 19, 2023, certain of our officers and directors were named as defendants in a shareholder derivative action filed in the Delaware Court
of Chancery. The complaint asserts, inter alia, breach of fiduciary duty claims arising from the facts underlying the securities class action related to
ROCTAVIAN. The complaint seeks unspecified monetary damages, internal governance reforms by the Company, attorneys fees and costs, and any other
relief the court may deem just and proper. We believe that the claims have no merit and we intend to vigorously defend this action.
55
On February 23, 2023, purported shareholders filed a lawsuit against us, our Chief Executive Officer, and our President of Worldwide Research and
Development in the United States District Court in the Northern District of California, alleging violations under Sections 10(b) and 20(a) of the Exchange Act
and a common law fraud claim. The complaint is similar to the ROCTAVIAN putative class action and largely premised on the same underlying facts. The
complaint seeks an unspecified amount of compensatory damages, punitive damages, prejudgment and post-judgment interest, attorneys’ fees and other
costs, and any further relief the court may deem just and proper. We believe that the claims have no merit and we intend to vigorously defend this action.
Item 4. Mine Safety Disclosures
Not applicable.
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Part II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Our common stock is listed under the symbol “BMRN” on the Nasdaq Global Select Market.
We have never paid any cash dividends on our common stock and we do not anticipate paying cash dividends in the foreseeable future.
Recent Sales of Unregistered Securities
We did not sell any unregistered securities during the year ended December 31, 2022.
Issuer Purchases of Equity Securities
None.
Holders
As of February 16, 2023, there were 35 holders of record of 186,528,784 outstanding shares of our common stock.
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Performance Graph
The following is not deemed “filed” with the Securities and Exchange Commission and is not to be incorporated by reference into any filing we make
under the Securities Act of 1933, as amended, whether made before or after the date hereof and irrespective of any general incorporation by reference
language in such filing.
The following graph shows the value of an investment in BioMarin common stock, the Nasdaq Composite Index, the Nasdaq Biotechnology Index,
and the Standard and Poor's (S&P) Depository Receipts S&P Biotech Exchange-traded Funds Index (SPDR S&P Biotech ETF), assuming the investment of
$100.00 at the beginning of the period and the reinvestment of dividends, if any. Our common stock is traded on the Nasdaq Global Select Market and is a
component of the Nasdaq Composite Index, the Nasdaq Biotechnology Index and the SPDR S&P Biotech ETF. The comparisons shown in the graph are
based upon historical data and we caution that the stock price performance shown in the graph is not indicative of, nor intended to forecast, the potential
future performance of our stock.
* $100 invested on December 31, 2017 in stock or index, including reinvestment of dividends
2017
2018
2019
2020
2021
2022
$
$
$
$
100.00 $
100.00 $
100.00 $
100.00 $
95.49 $
97.16 $
91.14 $
84.72 $
94.82 $
132.81 $
114.02 $
112.31 $
98.34 $
192.47 $
144.15 $
166.59 $
99.08 $
235.15 $
144.18 $
132.53 $
116.06
158.65
129.59
98.25
BioMarin Pharmaceutical Inc.
Nasdaq Composite Index
Nasdaq Biotechnology
SPDR S&P Biotech ETF
Item 6. [Reserved]
58
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following Management’s Discussion and Analysis of Financial Condition and Results of Operations (MD&A) is intended to help the reader
understand our results of operations and financial condition. MD&A is provided as a supplement to, and should be read in conjunction with, our audited
Consolidated Financial Statements and the accompanying notes to the Consolidated Financial Statements and other disclosures included in this Annual
Report on Form 10-K, including the disclosures under “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K. These risks and uncertainties
could cause actual results to differ significantly from those projected in forward-looking statements contained in this report or implied by past results and
trends. Forward-looking statements are statements that attempt to forecast or anticipate future developments in our business, financial condition or results of
operations. See the section titled “Forward-Looking Statements” that appears at the beginning of this Annual Report on Form 10-K. These statements, like
all statements in this report, speak only as of the date of this Annual Report on Form 10-K (unless another date is indicated), and, except as required by law,
we undertake no obligation to update or revise these statements in light of future developments. Our Consolidated Financial Statements have been prepared
in accordance with United States (U.S.) generally accepted accounting principles (GAAP) and are presented in U.S. Dollars (USD).
Overview
Founded in 1997, we are a global biotechnology company dedicated to transforming lives through genetic discovery. We develop and
commercialize targeted therapies that address the root cause of genetic conditions. Our robust research and development capabilities have resulted in
multiple innovative commercial therapies for patients with rare genetic disorders. Our distinctive approach to drug discovery has produced a diverse pipeline
of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity
to be first-to-market or offer a substantial benefit over existing treatment options. A summary of our commercial products, as of December 31, 2022, is
provided below:
Commercial Products
Products marketed by BioMarin:
VIMIZIM (elosulfase alpha)
NAGLAZYME (galsulfase)
PALYNZIQ (pegvaliase-pqpz)
KUVAN (sapropterin dihydrochloride)
VOXZOGO (vosoritide)
BRINEURA (cerliponase alfa)
ROCTAVIAN (valoctocogene roxaparvovec)
(2)
Products not marketed by BioMarin:
ALDURAZYME (laronidase)
Indication
(1)
MPS IVA
MPS VI
PKU
PKU
Achondroplasia
CLN2
Severe Hemophilia A
(4)
(3)
(5)
MPS I
(1)
(2)
(3)
(4)
(5)
Mucopolysaccharidosis
For the treatment of adult patients with phenylketonuria (PKU)
For the treatment of achondroplasia in children aged five years and older for the U.S., aged two years and older for the European Union (EU) and
for various age ranges for other markets
For the treatment of neuronal ceroid lipofuscinosis type 2
ROCTAVIAN (formerly known as valoctocogene roxaparvovec) for the treatment of adults with severe hemophilia A was conditionally approved by
the European Commission (EC) in August 2022
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
A summary of our clinical development programs as of December 31, 2022, is provided below:
Clinical Development Programs
ROCTAVIAN
BMN 255
BMN 331
(1) U.S. Food and Drug Administration
2022 Financial Highlights
Target
Indication
Severe Hemophilia A
Hyperoxaluria
Hereditary Angioedema (HAE)
(1)
Stage
FDA regulatory review
Clinical Phase 1/2
Clinical Phase 1/2
Key components of our results of operations include the following:
Total revenues
Cost of sales
Research and development (R&D) expense
Selling, general and administrative (SG&A) expense
Gain on sale of nonfinancial assets, net
Provision for (benefit from) income taxes
Net income (loss)
Years Ended December 31,
2021
2020
(1)
2022
2,096.0 $
483.7 $
649.6 $
854.0 $
(108.0) $
8.0 $
141.6 $
1,846.3 $
470.5 $
628.8 $
759.4 $
— $
(11.3) $
(64.1) $
1,860.5
524.3
628.1
737.7
(52.8)
(903.0)
854.0
$
$
$
$
$
$
$
(1)
Certain December 31, 2020 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
See “Results of Operations” below for discussion of our results for the periods presented.
Uncertainty Relating to Macroeconomic Environment
Conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange rates, natural disasters,
the continuing effects of the COVID-19 pandemic, and supply chain disruptions, could impact our global revenue sources and our overall business
operations. The extent and duration of such effects remain uncertain and difficult to predict. We are actively monitoring and managing our response and
assessing actual and potential impacts to our operating results and financial condition, as well as developments in our business, which could further impact
the developments, trends and expectations described below. See the risk factor, “Our business is affected by macroeconomic conditions.” described in “Risk
Factors” in Part I, Item 1A of this Annual Report on Form 10-K.
Business Developments
We continued to grow our commercial business and advance our product candidate pipeline during 2022. We believe that the combination of our
internal research programs, acquisitions and partnerships will allow us to continue to develop and commercialize innovative therapies for people with serious
and life-threatening rare diseases and medical conditions. Below is a summary of key business developments:
Continued Emphasis on Research and Development
New Product Launches, Approvals and Mid-stage Product Life Cycle Expansion Opportunities
•
VOXZOGO: The global expansion of VOXZOGO continues, with market access and reimbursement activities progressing as anticipated. As
of December 31, 2022, we have seen worldwide increases in the number of children being treated with commercial VOXZOGO and in the
number of active markets contributing to VOXZOGO sales.
During the fourth quarter, we submitted supplemental marketing applications in the U.S. and EU to expand VOXZOGO access to younger
age groups, based on favorable results from a Phase 2 study in infants and young
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
children. In January 2023, the European Medicines Agency (EMA) validated our application for extension of indications for VOXZOGO for
the treatment of children under the age of two. We expect action by U.S. and EU health authorities on the applications in the second half of
2023, and if accepted, this will increase the number of children eligible for VOXZOGO treatment in the U.S. and Europe.
•
ROCTAVIAN: Following conditional EMA approval in the third quarter of 2022, the European launch of ROCTAVIAN is underway. Since
approval, we continue to collaborate with German health insurers to secure novel Outcomes Based Agreements (OBAs) to enable access to
ROCTAVIAN treatment. The first OBA has been completed, allowing for a significant percentage of people in Germany affected by severe
hemophilia A to pursue treatment with ROCTAVIAN. Patient testing to determine eligibility for ROCTAVIAN treatment is ongoing throughout
Germany.
Our Biologics License Application (BLA) for ROCTAVIAN is currently under review by the FDA with a current Prescription Drug User Fee Act
(PDUFA) target action date of March 31, 2023, subject to a potential three-month extension, if deemed necessary during the review
procedure. We recently submitted to the FDA results from three or more years of follow up from our ongoing global Phase 3 GENEr8-1 study
of ROCTAVIAN, the largest and longest global Phase 3 study to date for any gene therapy in hemophilia with 134 participants. As part of the
ongoing review, the FDA completed the Pre-License Inspection of our dedicated gene therapy facility in December 2022. We have provided
responses to the comments and observations received at the close of the FDA inspection, and believe all are addressable. Also in the U.S.,
the Premarket Approval application is under review at the Center for Devices and Radiological Health to support contemporaneous approval
of a companion diagnostic (CDx) along with the ROCTAVIAN BLA.
Product expansion opportunities with ROCTAVIAN are supported by a number of clinical studies currently underway. Two additional studies
are ongoing, one investigating ROCTAVIAN treatment in those with active or prior inhibitors, as well as one study investigating ROCTAVIAN
in people with pre-existing antibodies against AAV5.
Select Earlier-stage Development Portfolio
•
•
BMN 255 for hyperoxaluria in chronic liver disease: We have concluded the multi-ascending dose phase of the First-in-Human study with
BMN 255. In January 2023, we shared early data that demonstrated a rapid and potent increase in plasma glycolate following treatment with
BMN 255, which is predicted to have a profound reduction in oxalate excretion in patients. We now plan to initiate and fully enroll an
expanded study in patients with chronic liver disease and hyperoxaluria in 2023. We believe the availability of a potent, orally bioavailable,
small molecule like BMN 255 may be able to significantly reduce disease and treatment burden in a patient population with significant unmet
need.
BMN 331 gene therapy product candidate for HAE: Dosing continues in the Phase 1/2 HAERMONY study to evaluate BMN 331, an
investigational AAV5-mediated gene therapy for people living with HAE. In January 2023, we shared that the first participant treated with the
6e13vg/kg dose demonstrated C1-Inhibitor levels that were approaching the therapeutically relevant range.
Reorganization Plan
On October 6, 2022, we announced our decision to redesign and simplify the organization to focus our resources on investments that advance our
R&D pipeline, maximize recent commercial launch success, prepare for commercial launch of ROCTAVIAN in the EU and potential U.S. launch, if approved
by the FDA, and drive core infrastructure optimization. As a result, there was a planned reduction in force of approximately 120 employees (representing
approximately 4% of our global workforce), most of whom are from our U.S. operations, and we incurred pre-tax severance and employee termination
benefit charges of $23.0 million in 2022.
2023 Outlook
We expect that our product pipeline investments and supporting our commercial infrastructure will enable us to execute on our 2023 operating
objectives. From an R&D perspective, we expect to continue to invest in our various ongoing clinical studies which support both our commercial products
and research and early development pipeline. We expect to move forward on our late and early-stage clinical studies for new product candidates, including
supporting the review of our BLA submission of ROCTAVIAN by the FDA. From a commercial perspective, we expect to continue to support our global
business as it grows, including support of the global commercialization of VOXZOGO and ROCTAVIAN in the EU.
We expect to experience growth in Net Product Revenues with respect to our new and other existing commercial products, with the exception of
KUVAN due to its loss of market exclusivity. We continue to monitor conditions in the macroeconomic environment that could affect our ability to achieve our
goals, such as changes in the reimbursement and payer landscape, changes in economic conditions in certain key markets throughout the world, market
competition and the launch of
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
generic competitors, international government pricing pressures and the potential volatility in foreign currency exchange rates. We will adjust our business
processes, as appropriate, to attempt to mitigate these risks to our business.
Critical Accounting Estimates
In preparing our Consolidated Financial Statements in accordance with U.S. GAAP and pursuant to the rules and regulations promulgated by the
Securities and Exchange Commission (the SEC), we make assumptions, judgments and estimates that can have a significant impact on our net income/loss
and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures. On an ongoing basis, we evaluate our
estimates and discuss our critical accounting policies and estimates with the Audit Committee of our Board of Directors. We base our estimates on historical
experience and various other assumptions that we believe to be reasonable under the circumstances. Actual results could differ materially from these
estimates under different assumptions or conditions. Historically, our assumptions, judgments and estimates relative to our critical accounting policies have
not differed materially from actual results.
Our significant accounting policies are described in Note 1 to our accompanying Consolidated Financial Statements included in this Annual Report
on Form 10-K. We believe the critical accounting policies below reflect the most critical judgments and estimates used in the preparation of our Consolidated
Financial Statements.
Revenue Recognition and Related Allowances
Net Product Revenues – We recognize revenue when the customer obtains control of promised goods or services, in an amount that reflects the
consideration which we expect to receive in exchange for those goods or services. For ALDURAZYME revenues, we receive a payment ranging from 39.5%
to 50% on worldwide net ALDURAZYME sales by Sanofi depending on sales volume, which is included in Net Product Revenues in our Consolidated
Statements of Operations. We recognize our best estimate of the entire revenue that we expect to receive when the product is released and control is
transferred to Sanofi. We record ALDURAZYME net product revenues based on the estimated variable consideration payable when the product is sold
through by Sanofi. Differences between the estimated variable consideration to be received from Sanofi and actual payments received are not expected to
be material. If actual results vary from our estimates, we will make adjustments, which would affect Net Product Revenues and earnings in the period such
variances become known.
Gross-to-Net Sales Adjustments – We record product sales net of estimated mandatory and supplemental discounts to government payers,
discounts to private payers and other related charges. Rebates, cash discounts and distributor fees represent the majority of our gross-to-net deductions and
are recorded in the same period the related sales occur. Rebates may include amounts paid to Medicaid or other U.S. or foreign government programs,
certain managed care providers, or other payers. Rebates, branded co-pay assistance programs, cash discounts and distributor fees are estimates based on
contractual arrangements or statutory obligations, which may vary by product and payer. Estimation requires evaluation of our actual historical experience,
customer mix, current contractual and statutory obligations, patient outcomes, specific known market events and trends and industry data. We evaluate our
customer mix to estimate which sales will be subject to these revenue dilutive items and consider changes to government program guidelines or contractual
obligations that would impact the actual rebates and/or our estimates of which sales qualify for such rebates. Any necessary adjustments to our reserves are
made each quarter to reflect current information. We believe the methodologies that we use to estimate allowances are reasonable and appropriate given
the facts and circumstances. However, actual results may differ significantly from our estimates.
The following table summarizes the consolidated activities and ending balances of all our gross-to-net sales adjustments:
Year ended December 31, 2022
Year ended December 31, 2021
Year ended December 31, 2020
Inventory Produced Prior to Regulatory Approval
Balance at
Beginning of Year
$
$
$
85.6 $
104.4 $
114.4 $
Provision for
Current Period
Sales
Payments
Balance at End of
Year
282.5 $
252.9 $
239.9 $
(253.1) $
(271.7) $
(249.9) $
115.0
85.6
104.4
When future commercialization for a product candidate is considered probable and management believes that material uncertainties related to the
ultimate regulatory approval have been significantly reduced and we expect to realize economic benefit in the future, we capitalize pre-launch or pre-
qualification manufacturing costs prior to regulatory approval. For inventories that are capitalized in preparation of product launch, management considers a
number of factors based on the information available at the time, including the product candidate’s current status in the drug development and regulatory
approval process, results from the related pivotal clinical trial, results from meetings with relevant regulatory agencies prior to the filing of regulatory
applications,
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
historical experience, as well as potential impediments to the approval process such as product safety or efficacy, as well as commercialization and market
trends.
In applying the lower of cost or net realizable value to pre-launch inventory, we estimate a range of likely commercial prices based on our
comparable commercial products and consider the product candidate’s stability data for all of the pre-approval production to date to determine whether there
is adequate expected shelf life for the capitalized pre-launch production costs. If additional requirements are subsequently presented by the regulatory
authorities prior to their final decision, thus extending anticipated regulatory approval timelines resulting in expiration of the product prior to revised demand
forecasts, as occurred in the third quarter of 2020 with ROCTAVIAN, the pre-launch inventory costs are expensed to Cost of Sales. If the marketing
application is ultimately rejected by the applicable regulators and the pre-launch inventory cannot be sold for commercial use, the pre-launch inventory costs
are expensed to R&D. As of December 31, 2022 and 2021, there were no pre-launch inventory costs on our Consolidated Balance Sheets.
Income Taxes
We calculate and provide for income taxes in each of the tax jurisdictions in which we operate. Our Consolidated Balance Sheets reflect net
deferred tax assets and liabilities, which are measured using enacted tax rates. The net deferred tax assets primarily represent the tax benefit of tax credits
and timing differences between book and tax recognition of certain revenue and expense items, net of a valuation allowance. When it is more likely than not
that all or some portion of deferred tax assets may not be realized, we establish a valuation allowance for the amount that may not be realized. We utilize
financial projections to support our net deferred tax assets, which contain significant assumptions and estimates of future operations. If such assumptions
were to differ significantly, it may have a material impact on our ability to realize our net deferred tax assets. Changes in our valuation allowance will result in
a change to tax expense.
We establish liabilities or reduce assets for certain tax positions when we believe those certain tax positions are not more likely than not to be
sustained if challenged. Each quarter, we evaluate these uncertain tax positions and adjust the related tax assets and liabilities in light of changing facts and
circumstances.
We are subject to income taxes in the U.S. and various foreign jurisdictions, including Ireland. Due to economic and political conditions, various
countries are actively considering changes to existing tax laws. We cannot predict the form or timing of potential legislative changes that could have a
material adverse impact on our results of operations. Management is not aware of any potential changes that would have a material effect on our
Consolidated Financial Statements. See Note 15 to our accompanying Consolidated Financial Statements for additional discussion.
Recent Accounting Pronouncements
See Note 1 to our accompanying Consolidated Financial Statements for a full description of recent accounting pronouncements and our expectation
of their impact, if any, on our results of operations and financial condition.
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
Results of Operations
Net Product Revenues
Net Product Revenues consisted of the following:
Net product revenues by product:
VIMIZIM
NAGLAZYME
PALYNZIQ
KUVAN
VOXZOGO
BRINEURA
FIRDAPSE
Total net product revenues marketed by us
ALDURAZYME net product revenues marketed
by Sanofi
Total net product revenues
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
$
$
$
663.8 $
443.8
255.0
227.6
169.1
154.3
—
1,913.6 $
128.4
2,042.0 $
623.1 $
380.4
237.5
285.8
5.9
128.0
—
1,660.7 $
122.8
1,783.5 $
544.4 $
391.3
171.0
457.7
—
110.2
1.2
1,675.8 $
130.1
1,805.9 $
40.7 $
63.4
17.5
(58.2)
163.2
26.3
—
252.9 $
5.6
258.5 $
78.7
(10.9)
66.5
(171.9)
5.9
17.8
(1.2)
(15.1)
(7.3)
(22.4)
The increase in Net Product Revenues in 2022 as compared to 2021 was primarily attributed to the following:
•
•
•
•
VOXZOGO: ramp up of commercial sales due to new patients initiating therapy globally following regulatory approvals in late 2021 and
2022;
NAGLAZYME and VIMIZIM: new patients initiating therapy and the timing of orders in countries that place large government orders,
particularly in Latin America, the Middle East and Europe; and
BRINEURA: higher sales primarily due to new patients initiating therapy globally; partially offset by
KUVAN: lower sales primarily attributed to increasing generic competition over time as a result of the loss of exclusivity in the U.S. that
occurred in October 2020.
In certain countries, governments place large periodic orders for our products. We expect that the timing of these large government orders will
continue to be inconsistent, which has created and may continue to create significant period to period variation in our revenues.
See the risk factor “The sale of generic versions of KUVAN by generic manufacturers has adversely affected and will continue to adversely affect
our revenues and may cause a decline in KUVAN revenues faster than expected” in “Risk Factors” included in Part I, Item 1A of this Annual Report for
additional information on risks we face.
We face exposure to movements in foreign currency exchange rates, primarily the Euro, which we expect to continue in future periods. We use
foreign currency exchange forward contracts to hedge a percentage of our foreign currency exposure. The following table shows our Net Product Revenues
denominated in USD and foreign currencies:
Sales denominated in USD
Sales denominated in foreign currencies
Total net product revenues
$
$
1,008.8 $
1,033.2
2,042.0 $
961.1 $
822.4
1,783.5 $
1,063.2 $
742.7
1,805.9 $
47.7 $
210.8
258.5 $
(102.1)
79.7
(22.4)
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
Favorable (unfavorable) impact of foreign currency
exchange rates on product sales denominated in
currencies other than USD
$
(59.0) $
2.3 $
(23.3) $
(61.3) $
25.6
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
Relative to the USD, the unfavorable impact in 2022 was primarily driven by weakening of the Euro, currencies from certain Latin American
markets, Japanese Yen and Turkish Lira.
See “Quantitative and Qualitative Disclosures about Market Risk” in Part II, Item 7A of this Annual Report on Form 10-K and the risk factor “Our
international operations pose currency risks, which may adversely affect our operating and net income” in “Risk Factors” included in Part I, Item 1A of this
Annual Report for information on currency exchange rate risk related to our Net Product Revenues.
Royalty and Other Revenues
Royalty and Other Revenues include royalties earned on net sales of products sold by third parties, up-front licensing fees, milestones achieved by
licensees or sublicensees and rental income associated with the tenants in our facilities.
Royalty and other revenues
$
54.0 $
62.8 $
54.6 $
(8.8) $
8.2
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
The decrease in Royalty and Other Revenues in 2022 as compared to 2021 was primarily due to the absence of license revenues earned from a
third party due to their achievement of a regulatory milestone in the first quarter of 2021.
We expect to continue to earn royalties from third parties in the future.
Cost of Sales and Gross Margin
Cost of Sales includes raw materials, personnel, facility and other costs associated with manufacturing our commercial products. These costs
include production materials, production costs at our manufacturing facilities, third-party manufacturing costs, amortization of technology transfer intangible
assets and internal and external final formulation and packaging costs. Cost of Sales also includes royalties payable to third parties based on sales of our
products and charges for inventory valuation reserves.
The following table summarizes our Cost of Sales and gross margin:
Total revenues
Cost of sales
Gross margin
2022
Years Ended December 31,
2021
2020
$
$
2,096.0
483.7
$
$
76.9 %
1,846.3
470.5
$
$
74.5 %
1,860.5
524.3
71.8 %
2022 vs. 2021
249.7
13.2
$
$
2021 vs. 2020
(14.2)
(53.8)
$
$
2.4 %
2.7 %
Cost of Sales increased for 2022 compared to 2021 primarily due to increased sales volumes. Gross margin for 2022 increased compared to 2021
primarily due to lower per unit manufacturing costs, lower inventory reserves and higher sales volume of products with higher margins.
We expect gross margin to range between 77.5% and 79% over the next twelve months.
Research and Development
R&D expense includes costs associated with the research and development of product candidates and post-marketing research commitments
related to our approved products. R&D expense primarily includes preclinical and clinical studies, personnel
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
and raw materials costs associated with manufacturing clinical product, quality control and assurance, other R&D activities, facilities and regulatory costs.
We manage our R&D expense by identifying the R&D activities we anticipate will be performed during a given period and then prioritizing efforts
based on scientific data, probability of successful development, market potential, available human and capital resources and other similar considerations.
We continually review our product pipeline and the development status of product candidates and, as necessary, reallocate resources among the research
and development portfolio that we believe will best support the future growth of our business.
We continuously evaluate the recoverability of costs associated with pre-launch or pre-qualification manufacturing activities, and capitalize the costs
incurred related to those activities if we determine that recoverability is highly likely and therefore future revenues are expected. If the related product
candidate's marketing application is rejected by the applicable regulators and the likelihood of future revenues for a product candidate become uncertain, the
related manufacturing costs are expensed as R&D expenses. We did not have any pre-launch or pre-qualification manufacturing activities capitalized in
inventory as of December 31, 2022 and 2021. See "Critical Accounting Estimates — Inventory Produced Prior to Regulatory Approval" above for additional
discussion.
R&D expense consisted of the following:
Research and early development
ROCTAVIAN
Other approved products
VOXZOGO
BMN 331
BMN 255
Other
Total R&D expense
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
$
$
264.3 $
119.0
115.8
101.0
29.9
9.0
10.6
649.6 $
213.8 $
115.1
108.5
129.3
38.0
8.7
15.4
628.8 $
186.8 $
116.2
133.7
130.8
42.2
8.6
9.8
628.1 $
50.5 $
3.9
7.3
(28.3)
(8.1)
0.3
(4.8)
20.8 $
27.0
(1.1)
(25.2)
(1.5)
(4.2)
0.1
5.6
0.7
R&D expense increased for 2022 compared to 2021 primarily due to the following:
•
•
higher spend in research and early development programs due to increased costs associated with manufacturing clinical product,
Investigational New Drug (IND)-enabling studies for planned IND filings and pre-clinical activities; partially offset by
a decrease in VOXZOGO related expenses due to capitalization of manufacturing costs and lower regulatory activity costs following the
regulatory approvals in the third and fourth quarters of 2021.
We expect R&D expense to increase in future periods compared to 2022, primarily due to higher spend on early research and clinical programs.
Selling, General and Administrative
Sales and marketing (S&M) expense primarily consisted of employee-related expenses for our sales group, brand marketing, patient support
groups and pre-commercialization expenses related to our product candidates. General and administrative (G&A) expense primarily consisted of corporate
support and other administrative expenses, including employee-related expenses.
SG&A expenses consisted of the following:
S&M expense
G&A expense
Total SG&A expense
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
$
$
450.3 $
403.7
854.0 $
405.1 $
354.3
759.4 $
403.4 $
334.3
737.7 $
45.2 $
49.4
94.6 $
1.7
20.0
21.7
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
S&M expenses by product were as follows:
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
PKU Products (Kuvan and Palynziq)
MPS Products (Aldurazyme, Naglazyme and
Vimizim)
VOXZOGO
ROCTAVIAN
BRINEURA
Other
Total S&M expense
$
$
122.7 $
124.6 $
127.5 $
104.3
102.3
73.6
31.4
16.0
450.3 $
102.9
75.1
54.0
36.2
12.3
405.1 $
108.1
34.5
87.3
37.8
8.2
403.4 $
(1.9) $
1.4
27.2
19.6
(4.8)
3.7
45.2 $
(2.9)
(5.2)
40.6
(33.3)
(1.6)
4.1
1.7
The increase in S&M expense for 2022 compared to 2021 was primarily a result of increased activities in 2022 in support of the VOXZOGO
commercial launch following EU and U.S. regulatory approvals in the latter half of 2021 and an increase in ROCTAVIAN commercial launch preparation
activities in connection with its conditional approval in the EU in August 2022.
The increase in G&A expense was primarily due to increased severance, employee termination benefits and external costs related to our
reorganization plan and higher legal expenses, partially offset by lower idle plant time related to maintaining our gene therapy manufacturing facility.
We expect SG&A expense to increase in future periods as we prepare to launch new products and support the expansion of our global brands.
Intangible Asset Amortization and Contingent Consideration and Gain on Sale of Nonfinancial Assets
Changes during the periods presented for Intangible Asset Amortization and Contingent Consideration and Gain on Sale of Nonfinancial Assets
were as follows:
Amortization of intangible assets
Changes in the fair value of contingent
consideration
Total intangible asset amortization and contingent
consideration
Gain on sale of nonfinancial assets
$
$
$
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
62.8 $
61.9 $
62.2 $
4.4
8.0
4.5
67.2 $
69.9 $
66.7 $
0.9 $
(3.6)
(2.7) $
(0.3)
3.5
3.2
108.0 $
— $
52.8 $
108.0 $
(52.8)
Amortization of intangible assets: the expense in 2022 as compared to 2021 was relatively flat.
Changes in the fair value of contingent consideration: the 2022 decrease in expense as compared to 2021 was attributable to the attainment of
milestones during the year equal to €45.0 million.
Gain on Sale of Nonfinancial Assets: the increase in 2022 as compared to 2021 was due to the sale in the first quarter of 2022 of the Priority
Review Voucher (PRV) that we received in connection with the FDA approval of VOXZOGO in 2021. In exchange for the PRV, we received a gross lump
sum payment of $110.0 million. This amount, net of broker fees, was recognized as a gain on the sale of intangible assets.
Interest Income
We invest our cash equivalents and investments in U.S. government securities and other high credit quality debt securities in order to limit default
and market risk.
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
Interest income
$
18.0 $
10.5 $
16.6 $
7.5 $
(6.1)
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
The increase in Interest Income during 2022 compared to 2021 was primarily due to higher interest rates and total portfolio returns.
We expect Interest Income to be higher over the next 12 months due to anticipated higher interest rates and yields on our cash equivalents and
investments.
Interest Expense
We incur interest expense primarily on our convertible debt. Interest Expense for the periods presented was as follows:
Interest expense
$
16.0 $
15.3 $
29.3 $
0.7 $
(14.0)
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
Interest Expense in 2022 was relatively flat compared to 2021. We do not expect Interest Expense to fluctuate significantly over the next 12 months
as the rates on our convertible debt are fixed. See Note 10 to our accompanying Consolidated Financial Statements for additional information regarding our
convertible debt.
Other Income (Expense), Net
Other Income (Expense), Net for the periods presented was as follows:
Other Income (Expense), net
$
(2.1) $
11.8 $
7.1 $
(13.9) $
4.7
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
The decrease in Other Income (Expense), Net in 2022 compared to 2021 was primarily due to the absence of insurance proceeds received in 2021
that were in excess of direct costs incurred as well as attributed to the loss on the fair value of assets held in our nonqualified deferred compensation
(NQDC) plan.
Provision for (Benefit from) Income Taxes
Provision for (Benefit from) Income Taxes for the periods presented was as follows:
Provision for (benefit from) income taxes
$
8.0 $
(11.3) $
(903.0) $
19.3 $
891.7
Years Ended December 31,
2021
2022
2020
2022 vs. 2021
2021 vs. 2020
Provision for (Benefit from) Income Taxes in 2022 increased compared to 2021, primarily due to taxes on higher income recognized, which includes
income recognized in the first quarter of 2022 from the sale of the PRV. Our Provision for (Benefit from) Income Taxes in 2022 and 2021 consisted of state,
federal and foreign current tax expense which was offset by tax benefits related to stock option exercises, foreign tax credits, and deferred tax benefits from
federal orphan drug credits and federal R&D credits. See Note 15 to our accompanying Consolidated Financial Statements for additional information.
Results of Operations 2021 Compared to 2020
For a discussion of our results of operations pertaining to 2021 as compared to 2020 see Item 7, "Management's Discussion and Analysis of
Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the year ended December 31, 2021.
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
Financial Condition, Liquidity and Capital Resources
Our cash, cash equivalents, and investments were as follows:
Cash and cash equivalents
Short-term investments
Long-term investments
Total cash, cash equivalents and investments
$
December 31, 2022
$
724.5 $
567.0
333.9
1,625.4 $
December 31, 2021
Change
587.3 $
426.6
507.8
1,521.7 $
137.2
140.4
(173.9)
103.7
We believe our cash generated from sales of our commercial products, in addition to our cash, cash equivalents and investments, will be sufficient
to satisfy our liquidity requirements for at least the next 12 months. We believe we will meet longer-term expected future cash requirements and obligations
through a combination of cash flows from operating activities, available cash and investments balances and available revolving loan balances. We will need
to raise additional funds from equity or debt securities, loans or collaborative agreements if we are unable to satisfy our liquidity requirements. For example,
we may require additional financing to fund the repayment of our convertible debt, future milestone payments and our future operations, including the
commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and
acquisitions. The timing and mix of our funding alternatives could change depending on many factors, including how much we elect to spend on our
development programs, potential licenses and acquisitions of complementary technologies, products and companies or if we settle our convertible debt in
cash.
We are mindful that conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange
rates, natural disasters, the continuing effects of the COVID-19 pandemic, and supply chain disruptions, could affect our ability to achieve our goals. In
addition, we sell our products in certain countries that face economic volatility and weakness. Although we have historically collected receivables from
customers in such countries, sustained weakness or further deterioration of the local economies and currencies may cause customers in those countries to
be unable to pay for our products. We will continue to monitor these conditions and will attempt to adjust our business processes, as appropriate, to mitigate
macroeconomic risks to our business.
Our cash flows for each of the years ended December 31, 2022 and 2021 were as follows:
Net cash provided by operating activities
Net cash used in investing activities
Net cash used in financing activities
2022
2021
2022 vs. 2021
$
$
$
175.9 $
(20.0) $
(18.7) $
304.5 $
(366.3) $
— $
(128.6)
346.3
(18.7)
The decrease in net cash provided by operating activities in 2022 compared to 2021 was primarily attributed to the timing of cash receipts from our
customers and the absence of a tax refund received in 2021.
The decrease in net cash used in investing activities in 2022 compared to 2021 was primarily attributable to lower net purchases of investments and
the $110.0 million gross proceeds from the sale of PRV in the first quarter of 2022.
The increase in net cash used by financing activities in 2022 compared to 2021 was primarily attributed to payments to a third party related to PKU
sales milestones that were achieved in 2022, partially offset by higher exercises of awards under our equity incentive plans.
Financing and Credit Facilities
Our $1.1 billion (undiscounted) of total convertible debt as of December 31, 2022 will impact our liquidity due to the semi-annual cash interest
payments as well as the repayment of the principal amount, if not converted. As of December 31, 2022, our indebtedness consisted of our 1.250% senior
subordinated convertible notes due in 2027 (the 2027 Notes) and our 0.599% senior subordinated convertible notes due in 2024 (the 2024 Notes and
together with the 2027 Notes, the Notes), which, if not converted, will be required to be repaid in cash at maturity in May 2027 and August 2024, respectively.
In October 2018, we entered into an unsecured revolving credit facility of up to $200.0 million that included a letter of credit subfacility and a
swingline loan subfacility. The credit facility is intended to finance ongoing working capital needs and for
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Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued)
(In millions of U.S. Dollars, except as otherwise disclosed)
other general corporate purposes. In May 2021, we amended the credit facility agreement, extending the maturity date from October 19, 2021 to May 28,
2024, among other changes. The amended credit facility contains financial covenants including a maximum leverage ratio and a minimum interest coverage
ratio. As of December 31, 2022, there were no outstanding amounts due on nor any usage of the credit facility and we were in compliance with all
covenants.
See Note 10 to our accompanying Consolidated Financial Statements for additional discussion on our convertible debt and credit facility.
Material Cash Requirements
Funding Commitments
Our investment in our research and early development of product candidates and continued development of our existing commercial products has a
major impact on our operating performance. R&D expenses for our commercial products and certain product candidates for the period since inception as of
December 31, 2022 were as follows:
ROCTAVIAN
VOXZOGO
BMN 331
BMN 255
Other approved products
Since Program
Inception
944.1
801.0
109.9
34.9
2,489.0
$
$
$
$
$
We cannot estimate with certainty the cost to complete any of our product development programs. We may need or elect to increase our spending
above our current long-term plans to be able to achieve our long-term goals. This may increase our capital requirements, including: costs associated with the
commercialization of our products; additional clinical trials; investments in the manufacturing of our commercial products; preclinical studies and clinical trials
for our product candidates; potential licenses and other acquisitions of complementary technologies, products and companies; and general corporate
purposes. Additionally, we cannot precisely estimate the time to complete any of our product development programs or when we expect to receive net cash
inflows from any of our product development programs. Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K, for a
discussion of the reasons we are unable to estimate such information.
Purchase and Lease Obligations
As of December 31, 2022, we had purchase obligations of approximately $225.5 million, of which $188.7 million is expected to be paid in 2023. Our
purchase obligations are primarily related to firm purchase commitments entered into in the normal course of business to procure active pharmaceutical
ingredients, certain inventory-related items, certain third-party R&D services, production services and facility construction services.
As of December 31, 2022, we had lease payment obligations of $42.3 million, of which $12.0 million is payable within the next 12 months. See Note
9 to our accompanying Consolidated Financial Statements for details on our lease liabilities.
Contingent Obligations
As of December 31, 2022, we had $15.9 million of acquisition-related contingent consideration on our Consolidated Balance Sheets related to our
achievement of a PKU sales milestone during the fourth quarter of 2022. The December 31, 2022 balance was subsequently paid in cash in the first quarter
of 2023. See Note 17 to our accompanying Consolidated Financial Statements for details on this arrangement.
As of December 31, 2022, we were subject to contingent payments considered reasonably possible of $762.5 million, including $381.5 million and
$210.0 million for two early-stage development programs licensed from third parties. See Note 18 to our accompanying Consolidated Financial Statements
for additional discussion on our contingent obligations.
Unrecognized Tax Benefits
As of December 31, 2022, our liability for unrecognized tax benefits was $232.9 million. Due to their nature, we cannot reasonably estimate the
timing of future payments. See Note 15 to our accompanying Consolidated Financial Statements for a full discussion on our income taxes.
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Item 7A. Quantitative and Qualitative Disclosure About Market Risk
We are exposed to market risks that may result from changes in foreign currency exchange rates, interest rates and credit risks. To reduce certain
of these risks, we enter into foreign currency derivative hedging transactions, follow investment guidelines and monitor outstanding trade receivables as part
of our risk management program.
Foreign Currency Exchange Rate Risk
Our operations include manufacturing activities in the U.S. and Ireland and sales activities in the U.S. as well as in regions outside the U.S,
including Europe, Latin America and Asia Pacific. As a result, our financial results may be significantly affected by factors such as changes in foreign
currency exchange rates or weak economic conditions in the foreign markets in which we sell our products. Our operating results are exposed to changes in
foreign currency exchange rates between the U.S. Dollar (USD) and various foreign currencies, primarily the Euro. When the USD strengthens against these
currencies, the relative value of the sales and operating expenses made in the respective foreign currency decreases. Conversely, when the USD weakens
against these currencies, the relative value of such sales and operating expenses increases. Overall, we are a net receiver of foreign currencies and,
therefore, benefit from a weaker USD and are adversely affected by a stronger USD relative to those foreign currencies in which we transact significant
business.
During 2022, approximately 51% of our net product sales were denominated in foreign currencies and 19% of our operating expenses, excluding
Cost of Sales, were denominated in foreign currencies. To partially mitigate the impact of changes in currency exchange rates on net cash flows from our
foreign currency denominated sales and operating expenses, we may enter into foreign currency exchange forward contracts (forward contracts). We also
hedge certain monetary assets and liabilities, primarily those denominated in Euros, using forward contracts, which reduces but does not eliminate our
exposure to currency fluctuations between the date the transaction is recorded and the date the cash is collected or paid. Generally, the market risks of
these contracts are offset by the corresponding gains and losses on the transactions being hedged.
We do not use derivative financial instruments for speculative trading purposes, nor do we hedge foreign currency exchange rate exposure in a
manner that entirely offsets the effects of changes in foreign currency exchange rates. The counterparties to these forward contracts are creditworthy
multinational commercial banks, which minimizes the risk of counterparty nonperformance. We regularly review our hedging program and may, as part of this
review, make changes to the program.
As of December 31, 2022, we had open forward contracts with net notional amounts of $843.4 million. A hypothetical 10% adverse movement in
foreign currency exchange rates compared with the USD relative to exchange rates as of December 31, 2022 would have resulted in a reduction in the value
received over the remaining life of these contracts by approximately $83.2 million on this date and, if realized, would negatively affect earnings during the
remaining life of the contracts. The estimated fair value change was determined by measuring the impact of the hypothetical exchange rate movement on
outstanding forward contracts. This analysis does not consider the impact of the hypothetical changes in foreign currency rates would have on the forecasted
transactions that these foreign currency sensitive instruments were designated to offset. Our use of this methodology to quantify the market risk of such
instruments is subject to assumptions and actual impact could be significantly different.
Based on our overall foreign currency denominated exposures as of December 31, 2022, we believe that a near-term 10% fluctuation of the USD
exchange rate could result in a potential change in the fair value of our net foreign currency denominated assets and liabilities, excluding our investments
and open forward contracts, by approximately $20.6 million. We expect to continue to enter into transactions based in foreign currencies that could be
impacted by changes in exchange rates.
Interest Rate Market Risk
Our exposure to market risk for changes in interest rates relates primarily to our investment portfolio, which includes our cash equivalents and
marketable debt securities. By policy, we place our investments with highly rated credit issuers and limit the amount of credit exposure to any one issuer. As
stated in our investment policy, we seek to improve the safety and likelihood of preservation of our invested funds by limiting default risk and market risk.
We mitigate default risk by investing in high credit quality securities and by positioning our portfolio to respond appropriately to a significant
reduction in a credit rating of any investment issuer or guarantor. The portfolio includes only marketable securities with active secondary or resale markets to
ensure portfolio liquidity.
We have outstanding $495.0 million (undiscounted) of the 2024 Notes and $600.0 million (undiscounted) of the 2027 Notes. The interest rates on
these notes are fixed and therefore they do not expose us to risk related to rising interest rates. As of December 31, 2022, the fair value of our convertible
debt was $1.2 billion.
As of December 31, 2022, our investment portfolio did not include any investments with significant exposure to countries that face economic
volatility and weakness. Although not predictive in nature, based on our investment portfolio and interest rates for the period ending December 31, 2022, we
believe a 100 basis point increase in interest rates could result in a potential loss in
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fair value of our investment portfolio of approximately $6.3 million. Changes in interest rates may affect the fair value of our investment portfolio. However,
we will not recognize such gains or losses in our Consolidated Statements of Operations unless the investments are sold or we determine that the declines
in the investment’s fair values below the cost basis are a result of a credit loss, which, if any, are reported in Other Income (Expense), Net in the current
period through an allowance for credit losses.
The table below summarizes the expected maturities and average interest rates of our interest-generating investments as of December 31, 2022 (in
millions of U.S. Dollars):
Available-for-sale debt securities
$
579.4
$
230.7
$
81.4
$
13.5
$
8.2
$
913.2
Average interest rate
4.2 %
5.1 %
5.1 %
4.9 %
4.3 %
4.5 %
2023
2024
Expected Maturity
2025
2026
2027
Total
Counterparty Credit Risks
Our financial instruments, including derivatives, are subject to counterparty credit risk that we consider as part of the overall fair value
measurement. Our financial risk management policy limits derivative transactions by requiring transactions to be with institutions with minimum credit ratings
of A- or equivalent by Standards & Poor’s, Moody's or Fitch. In addition, we have an investment policy that limits investments to certain types of debt and
money market instruments issued by institutions primarily with investment grade credit ratings and places restriction on maturities and concentrations by
asset class and issuer.
Item 8. Financial Statements and Supplementary Data
The information required to be filed in this item appears under “Exhibits, Financial Statement Schedules” in Part IV, Item 15 of this Annual Report on
Form 10-K.
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Evaluation of Disclosure Controls and Procedures
An evaluation was carried out, under the supervision of and with the participation of our management, including our Chief Executive Officer and our
Chief Financial Officer, of the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act)
as of the end of the period covered by this report. Based on the evaluation, our Chief Executive Officer and our Chief Financial Officer have concluded that
our disclosure controls and procedures were effective as of December 31, 2022.
Management’s Annual Report on Internal Control Over Financial Reporting
Our management is responsible for establishing and maintaining an adequate internal control structure and procedures for financial reporting.
Under the supervision of and with the participation of our management, including our Chief Executive Officer and our Chief Financial Officer, our
management has assessed the effectiveness of our internal control over financial reporting as defined in Rule 13a-15(f) under the Exchange Act as of
December 31, 2022. Our management’s assessment was based on criteria set forth by the Committee of Sponsoring Organizations of the Treadway
Commission (COSO), Internal Control-Integrated Framework (2013).
Based on the COSO criteria, our management has concluded that our internal control over financial reporting as of December 31, 2022 was
effective at the reasonable assurance level.
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Our independent registered public accounting firm, KPMG LLP, has audited the financial statements included in this Annual Report on Form 10-K
and has issued a report on the effectiveness of our internal control over financial reporting. The report of KPMG LLP is incorporated by reference to Item 8 of
this Annual Report on Form 10-K.
Changes in Internal Control Over Financial Reporting
There were no changes in our internal control over financial reporting, as such term is defined in Rules 13a-15(f) and 15d-15(f) under the Exchange
Act, during our most recently completed quarter that have materially affected or are reasonably likely to materially affect our internal control over financial
reporting. We continue to utilize the Committee of Sponsoring Organizations of the Treadway Commission (COSO) 2013 Framework on internal control.
Scope of the Effectiveness of Controls
Our internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and
the preparation of financial statements for external purposes in accordance with GAAP. Our internal control over financial reporting includes those policies
and procedures that:
•
•
•
pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect our transactions and dispositions of our assets;
provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance
with GAAP, and that our receipts and expenditures are being made only in accordance with authorizations of our management and our
board of directors; and
provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of our assets that
could have a material effect on our financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any
evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions or that the degree
of compliance with the policies or procedures may deteriorate.
Item 9B. Other Information
None.
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Not applicable.
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Item 10. Directors, Executive Officers and Corporate Governance
Part III
The information required by this Item regarding our directors, executive officers and corporate governance is incorporated into this section by
reference to the sections captioned “Election of Directors” and “Executive Officers” in the proxy statement for our 2023 annual meeting of stockholders.
Item 11. Executive Compensation
The information required by this Item regarding executive compensation is incorporated into this section by reference to the section captioned
“Executive Compensation” in the proxy statement for our 2023 annual meeting of stockholders.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required by this Item regarding security ownership of our beneficial owners, management and related stockholder matters is
incorporated into this section by reference to the section captioned “Security Ownership of Certain Beneficial Owners and Management” in the proxy
statement for our 2023 annual meeting of stockholders.
The information required by this Item regarding the securities authorized for issuance under our equity compensation plans is incorporated into this
section by reference to the section captioned “Equity Compensation Plan Information” in the proxy statement for our 2023 annual meeting of stockholders.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this Item regarding certain relationships, related transactions and director independence is incorporated into this
section by reference to the sections captioned “Other Board Governance Information — Transactions with Related Persons, Promoters and Certain Control
Persons,” “Other Board Governance Information — Review, Approval and Ratification of Transactions with Related Parties” and “Director Independence” in
the proxy statement for our 2023 annual meeting of stockholders.
Item 14. Principal Accountant Fees and Services
The information required by this Item regarding our principal accountant fees and services is incorporated into this section by reference to the
section captioned “Independent Registered Public Accounting Firm” in the proxy statement for our 2023 annual meeting of stockholders.
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Item 15. Exhibits, Financial Statement Schedules
Exhibit Index
Financial Statements
Part IV
Reports of Independent Registered Public Accounting Firm (KPMG LLP, San Francisco, CA, Auditor Firm ID: 185)
Consolidated Financial Statements as of December 31, 2022 and 2021, and for the three years ended December 31, 2022:
Consolidated Balance Sheets
Consolidated Statements of Operations
Consolidated Statements of Comprehensive Income (Loss)
Consolidated Statements of Changes in Stockholders’ Equity
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
75
Page
76
83
86
87
88
89
90
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Exhibit Index
Exhibit Number
Description
2.1
2.2
2.3
3.1
3.2
4.1
4.2
4.3
4.4
10.1†
10.2†
10.3†
10.4†
10.5†
Amended and Restated Termination and Transition Agreement, dated as of December 23, 2015, between BioMarin Pharmaceutical
Inc. and Ares Trading S.A., previously filed with the SEC on January 7, 2016 as Exhibit 2.1 to the Company’s Current Report on
Form 8-K (File No. 000-26727), which is incorporated herein by reference. Portions of this exhibit (indicated by asterisks) have been
omitted pursuant to a request for confidential treatment. Omitted portions have been filed separately with the SEC.
Termination and Transition Agreement, dated as of October 1, 2015, between BioMarin Pharmaceutical Inc. and Ares Trading S.A.,
previously filed with the SEC on January 7, 2016 as Exhibit 2.3 to the Company’s Current Report on Form 8-K (File No. 000-26727),
which is incorporated herein by reference. Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request
for confidential treatment. Omitted portions have been filed separately with the SEC.
First Amendment, dated as of December 12, 2016, to the Amended and Restated Termination and Transition Agreement, dated as
of December 23, 2015 and effective as of October 1, 2015, between BioMarin Pharmaceutical Inc. and Ares Trading S.A.,
previously filed with the SEC on February 27, 2017 as Exhibit 2.6 to the Company’s Annual Report on Form 10-K (File No. 000-
26727), which is incorporated herein by reference. Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a
request for confidential treatment. Omitted portions have been filed separately with the SEC.
Restated Certificate of Incorporation of BioMarin Pharmaceutical Inc., previously filed with the SEC on June 12, 2017 as Exhibit 3.2
to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by reference.
Amended and Restated Bylaws of BioMarin Pharmaceutical Inc., previously filed with the SEC on December 21, 2022 as Exhibit 3.1
to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by reference.
Base Indenture, dated August 11, 2017, between the Company and Wilmington Trust, National Association, as Trustee, previously
filed with the SEC on August 11, 2017 as Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is
incorporated herein by reference.
First Supplemental Indenture, dated August 11, 2017, between the Company and Wilmington Trust, National Association, as
Trustee (including the form of 0.599% Senior Subordinated Convertible Note due 2024), previously filed with the SEC on August 11,
2017 as Exhibit 4.2 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by reference.
Indenture, dated as of May 14, 2020, between BioMarin Pharmaceutical Inc. and U.S. Bank National Association, as trustee,
including the Form of Global Note representing BioMarin Pharmaceutical, Inc.’s 1.25% Senior Subordinated Convertible Notes due
2027 as Exhibit A thereto, previously filed with the SEC on May 14, 2020 as Exhibit 4.1 to the Company’s Current Report on Form
8-K (File No. 000-26727), which is incorporated herein by reference.
Description of Capital Stock, previously filed with the SEC on February 27, 2020 as Exhibit 4.6 to the Company’s Annual Report on
Form 10-K (File No. 000-26727), which is incorporated herein by reference.
Form of Indemnification Agreement for Directors and Officers, previously filed with the SEC on December 19, 2016 as Exhibit 10.1
to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by reference.
BioMarin Pharmaceutical Inc. Amended and Restated 2006 Employee Stock Purchase Plan, as amended and restated April 12,
2019, previously filed with the SEC on August 2, 2019 as Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No.
000-26727), which is incorporated herein by reference.
BioMarin Pharmaceutical Inc. Amended and Restated 2006 Share Incentive Plan, as adopted on May 2, 2006 and as amended and
restated on April 16, 2015, previously filed with the SEC on June 15, 2015 as Exhibit 10.1 to the Company’s Current Report on
Form 8-K (File No. 000-26727), which is incorporated herein by reference.
Form of Agreement Regarding Restricted Share Units for the BioMarin Pharmaceutical Inc. 2006 Share Incentive Plan, previously
filed with the SEC on May 16, 2013 as Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is
incorporated herein by reference.
Form of Amendment to Agreement Regarding Restricted Share Units for the BioMarin Pharmaceutical Inc. 2006 Share Incentive
Plan, previously filed with the SEC on December 9, 2016 as Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No.
000-26727), which is incorporated herein by reference.
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Table of Contents
10.6†
10.7†
10.8
10.9
10.10
10.11
10.12
10.13†
10.14†
10.15†
10.16
10.17†
10.18†
10.19†
10.20†
10.21
Amended and Restated BioMarin Pharmaceutical Inc. Nonqualified Deferred Compensation Plan, as adopted on December 1, 2005
and as amended and restated on January 1, 2009 and further amended and restated on December 19, 2013 and October 7, 2014,
previously filed with the SEC on October 14, 2014 as Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 000-
26727), which is incorporated herein by reference.
Amended and Restated Employment Agreement with Jean-Jacques Bienaimé effective December 13, 2016 previously filed with the
SEC on December 19, 2016 as Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is
incorporated herein by reference.
License Agreement dated July 30, 2004, between BioMarin Pharmaceutical Inc. and Daiichi Suntory Pharma Co., Ltd., as amended
by Amendment No. 1 to License Agreement dated November 19, 2004, previously filed with the SEC on March 16, 2005 as Exhibit
10.25 to the Company’s Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein by reference. The SEC
has granted confidential treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with
the SEC.
Operating Agreement with Genzyme Corporation, previously filed with the SEC on July 6, 1999 as Exhibit 10.30 to the Company’s
Amendment No. 2 to Registration Statement on Form S-1 (File No. 333-77701), which is incorporated herein by reference.
Manufacturing, Marketing and Sales Agreement dated as of January 1, 2008, by and among BioMarin Pharmaceutical Inc.,
Genzyme Corporation and BioMarin/Genzyme LLC previously filed with the SEC on February 28, 2008 as Exhibit 10.30 to the
Company’s Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein by reference. The SEC has granted
confidential treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with the SEC.
Amended and Restated Collaboration Agreement dated as of January 1, 2008, by and among BioMarin Pharmaceutical Inc.,
Genzyme Corporation and BioMarin/Genzyme LLC previously filed with the SEC on February 28, 2008 as Exhibit 10.31 to the
Company’s Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein by reference. The SEC has granted
confidential treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with the SEC.
Members Agreement dated as of January 1, 2008 by and among BioMarin Pharmaceutical Inc., Genzyme Corporation, BioMarin
Genetics Inc., and BioMarin/Genzyme LLC previously filed with the SEC on February 28, 2008 as Exhibit 10.32 to the Company’s
Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein by reference. The SEC has granted confidential
treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with the SEC.
BioMarin Pharmaceutical Inc. 2012 Inducement Plan, adopted May 8, 2012, previously filed with the SEC on May 9, 2012 as Exhibit
10.2 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by reference.
Form of Stock Options Agreement for the BioMarin Pharmaceutical Inc. 2006 Share Incentive Plan. (as Amended and Restated
2010), previously filed with the SEC on August 2, 2012 as Exhibit 10.11 to the Company’s Quarterly Report on Form 10-Q (File No.
000-26727), which is incorporated herein by reference.
Form of Stock Options Agreement for the BioMarin Pharmaceutical Inc. 2012 Inducement Plan, previously filed with the SEC on
August 2, 2012 as Exhibit 10.13 to the Company’s Quarterly Report on Form 10-Q (File No. 000-26727), which is incorporated
herein by reference.
Contract of Purchase and Sale and Joint Escrow Instructions, dated December 17, 2013, for the San Rafael Corporate Center, by
and among BioMarin Pharmaceutical Inc., through its wholly-owned subsidiary, California Corporate Center Acquisition, LLC, SR
Corporate Center Phase One, LLC, and SR Corporate Center Phase Two, previously filed with the SEC on February 26, 2014 as
Exhibit 10.68 to the Company’s Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein by reference.
BioMarin Pharmaceutical Inc. 2014 Inducement Plan, adopted December 17, 2014, previously filed with the SEC on December 23,
2014 as Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by
reference.
Form of Stock Options Agreement for the BioMarin Pharmaceutical Inc. 2014 Inducement Plan, previously filed with the SEC on
March 2, 2015 as Exhibit 10.60 to the Company’s Annual Report on Form 10-K (File No. 000-26727), which is incorporated herein
by reference.
Form of Agreement Regarding Restricted Share Units for the BioMarin Pharmaceutical Inc. 2014 Inducement Plan, previously filed
with the SEC on March 2, 2015 as Exhibit 10.61 to the Company’s Annual Report on Form 10-K (File No. 000-26727), which is
incorporated herein by reference.
Form of Amended and Restated Employment Agreement for the Company’s Executive Officers (other than the Company’s Chief
Executive Officer) previously filed with the SEC on June 15, 2015 as Exhibit 10.2 to the Company’s Current Report on Form 8-K
(File No. 000-26727), which is incorporated herein by reference.
Settlement and License Agreement among BioMarin Pharmaceutical Inc., Merck & Cie, Dr. Reddy’s Laboratories, Inc. and Dr.
Reddy’s Laboratories, Ltd., dated September 14, 2015, previously filed with the SEC on November 2, 2015 as Exhibit 10.2 to the
Company’s Quarterly Report on Form 10-Q (File No. 000-26727), which is incorporated herein by reference. The SEC has granted
confidential treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with the SEC.
77
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10.22
10.23†
10.24†
10.25†
10.26†
10.27†
10.28†
10.29
10.30
10.31†
10.32†
10.33
10.34†
10.35†*
10.36†*
10.37†*
21.1*
Settlement and License Agreement among BioMarin Pharmaceutical Inc., Merck & Cie and Par Pharmaceutical, Inc., dated as of
April 12, 2017, previously filed with the SEC on November 13, 2017 as Exhibit 10.1 to the Company’s Amendment No. 1 to
Quarterly Report on Form 10-Q/A (File No. 000-26727), which is incorporated herein by reference. The SEC has granted
confidential treatment with respect to certain portions of this exhibit. Omitted portions have been filed separately with the SEC.
Form of Agreement Regarding Performance Stock Award in the Form of Restricted Stock Units for the BioMarin Pharmaceutical Inc.
2006 Share Incentive Plan, previously filed with the SEC on February 27, 2017 as Exhibit 10.50 to the Company’s Annual Report on
Form 10-K (File No. 000-26727), which is incorporated herein by reference.
BioMarin Pharmaceutical Inc. 2017 Equity Incentive Plan, as adopted April 10, 2017 and amended April 5, 2021, previously filed
with the SEC on February 17, 2022 as Exhibit 99.1 to the Company’s Registration Statement on Form S-8 (File No. 333-262824),
which is incorporated herein by reference.
Form of Stock Options Agreement for the BioMarin Pharmaceutical Inc. 2017 Equity Incentive Plan, previously filed with the SEC on
June 12, 2017 as Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is incorporated herein by
reference.
Form of Agreement Regarding Restricted Stock Units for the BioMarin Pharmaceutical Inc. 2017 Equity Incentive Plan, previously
filed with the SEC on June 12, 2017 as Exhibit 10.3 to the Company’s Current Report on Form 8-K (File No. 000-26727), which is
incorporated herein by reference.
Form of Agreement Regarding Performance Stock Award in the Form of Restricted Stock Units for the BioMarin Pharmaceutical Inc.
2017 Equity Incentive Plan, previously filed with the SEC on June 12, 2017 as Exhibit 10.4 to the Company’s Current Report on
Form 8-K (File No. 000-26727), which is incorporated herein by reference.
BioMarin Pharmaceutical Inc. Summary of Independent Director Compensation, previously filed with the SEC on October 28, 2022
as Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 000-26727), which is incorporated herein by reference.
Credit Agreement by and among BioMarin Pharmaceutical Inc., as the Borrower, Bank of America, N.A., as Administrative Agent,
Swing Line Lender and a Lender, and Citibank N.A. as L/C Issuer, and the Lenders party thereto, dated as of October 19, 2018,
previously filed with the SEC on February 28, 2019 as Exhibit 10.48 to the Company’s Annual Report on Form 10-K (File No. 000-
26727), which is herein incorporated by reference.
First Amendment, dated May 28, 2021, to the Credit Agreement by and among BioMarin Pharmaceutical Inc., as the Borrower,
Bank of America, N.A., as Administrative Agent, Swing Line Lender and a Lender, and Citibank N.A. as L/C Issuer, and the Lenders
party thereto, previously filed with the SEC on July 30, 2021 as Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File
No. 000-26727), which is incorporated herein by reference.
First Amendment to the Amended and Restated BioMarin Pharmaceutical Inc. Nonqualified Deferred Compensation Plan, as
adopted June 4, 2019, previously filed with the SEC on August 2, 2019 as Exhibit 10.1 to the Company’s Quarterly Report on
Form 10-Q (File No. 000-26727), which is incorporated herein by reference.
Second amendment to the Amended and Restated BioMarin Pharmaceutical Inc. Nonqualified Deferred Compensation Plan, as
adopted on October 5, 2021, previously filed with the SEC on February 25, 2022 as Exhibit 10.32 to the Company’s Annual Report
on Form 10-K (File No. 000-26727), which is incorporated herein by reference.
Asset Purchase Agreement by and between Eli Lilly and Company, BioMarin Pharmaceutical Inc., and BioMarin International Ltd.,
dated February 8, 2022, previously filed with the SEC on April 29, 2022 as Exhibit 10.1 to the Company’s Quarterly Report on Form
10-Q (File No. 000-26727), which is incorporated herein by reference. Portions of this exhibit have been omitted because they are
not material and the type that the registrant treats as private or confidential.
Third Amendment to the Amended and Restated BioMarin Pharmaceutical Inc. Nonqualified Deferred Compensation Plan, as
adopted October 4, 2022, previously filed with the SEC on October 28, 2022 as Exhibit 10.1 to the Company’s Quarterly Report on
Form 10-Q (File No. 000-26727), which is incorporated herein by reference.
Form of Agreement Regarding Non-Employee Director Restricted Stock Units for the BioMarin Pharmaceutical Inc. 2017 Equity
Incentive Plan.
Form of Agreement Regarding Restricted Stock Units for the BioMarin Pharmaceutical Inc. 2017 Equity Incentive Plan.
Form of Stock Options Agreement for the BioMarin Pharmaceutical Inc. 2017 Equity Incentive Plan.
Subsidiaries of BioMarin Pharmaceutical Inc.
78
Table of Contents
23.1*
24.1*
31.1*
31.2*
32.1*
101.INS
101.SCH
101.CAL
101.DEF
101.LAB
101.PRE
104
Consent of KPMG LLP, Independent Registered Public Accounting Firm for BioMarin Pharmaceutical Inc.
Power of Attorney (Included in Signature Page to this Report)
Certification of Chief Executive Officer pursuant to Rules 13a-14(a)/15d-14(a) of the Securities Exchange Act of 1934, as amended.
Certification of Chief Financial Officer pursuant to Rules 13a-14(a)/15d-14(a) of the Securities Exchange Act of 1934, as amended.
Certification of Chief Executive Officer and Chief Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to
Section 906 of the Sarbanes-Oxley Act of 2002. This Certification accompanies this report and shall not, except to the extent
required by the Sarbanes-Oxley Act of 2002, be deemed filed for purposes of §18 of the Securities Exchange Act of 1934, as
amended.
XBRL Instance Document - the instance document does not appear in the Interactive Data File because its XBRL tags are
embedded within the Inline XBRL document.
Inline XBRL Taxonomy Extension Schema Document
Inline XBRL Taxonomy Extension Calculation Document
Inline XBRL Taxonomy Extension Definition Linkbase
Inline XBRL Taxonomy Extension Labels Linkbase Document
Inline XBRL Taxonomy Extension Presentation Link Document
XBRL tags for the cover page from the Company’s Quarterly Report on Form 10-K for the year ended December 31, 2022, are
embedded within the Inline XBRL document.
* Filed herewith
† Management contract or compensatory plan or arrangement
Attached as Exhibit 101 to this report are documents formatted in XBRL (Extensible Business Reporting Language): (i) Consolidated Balance
Sheets as of December 31, 2022 and December 31, 2021, (ii) Consolidated Statements of Operations for the years ended December 31, 2022, 2021 and
2020, (iii) Consolidated Statements of Comprehensive Income (Loss) for the years ended December 31, 2022, 2021 and 2020, (iv) Consolidated Statements
of Stockholders’ Equity for the years ended December 31, 2022, 2021 and 2020, (v) Consolidated Statements of Cash Flows for the years ended
December 31, 2022, 2021 and 2020, and (vi) Notes to Consolidated Financial Statements.
Item 16. Form 10-K Summary
None.
79
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SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed
on its behalf by the undersigned, thereunto duly authorized.
Dated: February 27, 2023
By:
/S/ BRIAN R. MUELLER
Brian R. Mueller
Executive Vice President, Finance & Chief Financial Officer
BIOMARIN PHARMACEUTICAL INC.
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POWER OF ATTORNEY
Exhibit 24.1
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Jean-Jacques
Bienaimé and Brian R. Mueller, his or her attorney-in-fact, with the power of substitution, for him or her in any and all capacities, to sign any amendments to
the Report on Form 10-K and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange
Commission, hereby ratifying and confirming all that each of said attorneys-in-fact, or his substitute or substitutes, may do or cause to be done by virtue
hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the
registrant and in the capacities and on the dates indicated:
Signature
/S/ JEAN-JACQUES BIENAIMÉ
Jean-Jacques Bienaimé
Title
Chairman and Chief Executive Officer
(Principal Executive Officer)
/S/ BRIAN R. MUELLER
Brian R. Mueller
/S/ ERIN BURKHART
Erin Burkhart
/S/ MARK J. ALLES
Mark J. Alles
Executive Vice President, Finance & Chief Financial
Officer
(Principal Financial Officer)
Group Vice President, Chief Accounting Officer
(Principal Accounting Officer)
Director
/S/ ELIZABETH MCKEE ANDERSON
Director
Elizabeth McKee Anderson
/S/ WILLARD H. DERE, M.D.
Director
Willard H. Dere, M.D.
/S/ ELAINE J. HERON
Elaine J. Heron
/S/ MAYKIN HO
Maykin Ho
/S/ ROBERT J. HOMBACH
Robert J. Hombach
/S/ V. BRYAN LAWLIS
V. Bryan Lawlis
Director
Director
Director
Director
Date
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
February 27, 2023
/S/ RICHARD A. MEIER
Lead Independent Director
February 27, 2023
Richard A. Meier
/S/ DAVID PYOTT
David Pyott
/S/ DENNIS J. SLAMON
Dennis J. Slamon
Director
Director
81
February 27, 2023
February 27, 2023
Table of Contents
BIOMARIN PHARMACEUTICAL INC.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Reports of Independent Registered Public Accounting Firm (KPMG LLP, San Francisco, CA, Firm ID: 185)
Consolidated Financial Statements as of December 31, 2022 and 2021, and for the three years ended December 31, 2022:
Consolidated Balance Sheets
Consolidated Statements of Operations
Consolidated Statements of Comprehensive Income (Loss)
Consolidated Statements of Stockholders’ Equity
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
PAGE
83
86
87
88
89
90
91
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Table of Contents
Report of Independent Registered Public Accounting Firm
To the Stockholders and Board of Directors
BioMarin Pharmaceutical Inc.:
Opinion on the Consolidated Financial Statements
We have audited the accompanying consolidated balance sheets of BioMarin Pharmaceutical Inc. and subsidiaries (the Company) as of December 31, 2022
and December 31, 2021, the related consolidated statements of operations, comprehensive income (loss), stockholders’ equity, and cash flows for each of
the years in the three-year period ended December 31, 2022, and the related notes (collectively, the consolidated financial statements). In our opinion, the
consolidated financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 2022 and December 31,
2021, and the results of its operations and its cash flows for each of the years in the three-year period ended December 31, 2022, in conformity with U.S.
generally accepted accounting principles.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company’s
internal control over financial reporting as of December 31, 2022, based on criteria established in Internal Control – Integrated Framework (2013) issued by
the Committee of Sponsoring Organizations of the Treadway Commission, and our report dated February 27, 2023 expressed an unqualified opinion on the
effectiveness of the Company’s internal control over financial reporting.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on these
consolidated financial statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with
respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange
Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. Our audits included
performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing
procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the
consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as
well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was
communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the consolidated
financial statements and (2) involved our especially challenging, subjective, or complex judgments. The communication of a critical audit matter does not
alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below,
providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.
Evaluation of variable consideration relating to ALDURAZYME product sales
As described in Notes 1 and 12 to the consolidated financial statements, during the year ended December 31, 2022 the Company recognized $128 million in
ALDURAZYME net product revenue. Under its arrangement with Sanofi, the Company receives payments ranging from 39.5% to 50% on worldwide net
ALDURAZYME sales by Sanofi, depending on Sanofi’s sales volume. The Company estimates this variable consideration based on the amount that it
expects to be entitled to from Sanofi’s sales of ALDURAZYME. The Company recognizes this revenue upon satisfying the product performance obligation,
which is when the product is shipped to Sanofi and all required quality control certificates are complete.
We identified the evaluation of variable consideration relating to ALDURAZYME net product revenue as a critical audit matter. Evaluating the key
assumptions of forecasted Sanofi sales volume and average price per vial involved a high degree of subjective auditor judgment due to the nature of
available supporting evidence being limited to Sanofi sales forecasts and historical sales and price data. Changes in these key assumptions could have had
a significant impact on ALDURAZYME net product revenue.
The following are the primary procedures we performed to address this critical audit matter. We evaluated the design and tested the operating effectiveness
of certain internal controls related to the Company’s process for recognizing ALDURAZYME net product revenue. This included controls over forecasting
Sanofi’s sales volume and average price per vial used to estimate variable
83
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Report of Independent Registered Public Accounting Firm
consideration. We evaluated the Company’s ability to estimate the variable consideration by comparing historical estimates of sales volume and price per
vial to actual sales volume and price per vial of product sold by Sanofi. We also compared the Company’s current-period forecasts of future Sanofi sales
volume and average price per vial to Sanofi’s historical sales volume and price per vial. We performed a sensitivity analysis to assess the impact of changes
in these key assumptions on the Company’s estimate of variable consideration.
/s/ KPMG LLP
We have served as the Company’s auditor since 2002.
San Francisco, California
February 27, 2023
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Report of Independent Registered Public Accounting Firm
To the Stockholders and Board of Directors
BioMarin Pharmaceutical Inc.:
Opinion on Internal Control Over Financial Reporting
We have audited BioMarin Pharmaceutical Inc. and subsidiaries' (the Company) internal control over financial reporting as of December 31, 2022, based on
criteria established in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission. In
our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31, 2022, based on criteria
established in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidated
balance sheets of the Company as of December 31, 2022 and December 31, 2021, the related consolidated statements of operations, comprehensive
income (loss), stockholders’ equity, and cash flows for each of the years in the three-year period ended December 31, 2022, and the related notes
(collectively, the consolidated financial statements), and our report dated February 27, 2023 expressed an unqualified opinion on those consolidated financial
statements.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of
internal control over financial reporting, included in the accompanying Management's Annual Report on Internal Control over Financial Reporting. Our
responsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We are a public accounting firm
registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the
applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit of internal control over financial
reporting included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and
evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audit also included performing such other procedures
as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.
Definition and Limitations of Internal Control Over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and
the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over
financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect
the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit
preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are
being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding
prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial
statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of
effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of
compliance with the policies or procedures may deteriorate.
/s/ KPMG LLP
San Francisco, California
February 27, 2023
85
Table of Contents
Current assets:
Cash and cash equivalents
Short-term investments
Accounts receivable, net
Inventory
Other current assets
Total current assets
Noncurrent assets:
Long-term investments
Property, plant and equipment, net
Intangible assets, net
Goodwill
Deferred tax assets
Other assets
BIOMARIN PHARMACEUTICAL INC.
CONSOLIDATED BALANCE SHEETS
December 31, 2022 and 2021
(In thousands of U.S. Dollars, except share and per share amounts)
ASSETS
December 31,
2022
December 31,
2021 ⁽¹⁾
$
$
$
$
724,531 $
567,006
461,316
894,083
104,521
2,751,457
333,835
1,073,366
338,569
196,199
1,505,412
176,236
6,375,074 $
572,959 $
15,925
588,884
1,083,019
—
100,015
1,771,918
186
5,404,895
(8,859)
(3,867)
(789,199)
4,603,156
6,375,074 $
587,276
426,599
373,399
776,669
110,442
2,274,385
507,793
1,035,461
388,652
196,199
1,450,161
152,121
6,004,772
498,265
48,232
546,497
1,079,077
15,167
98,362
1,739,103
184
5,191,502
(9,689)
14,432
(930,760)
4,265,669
6,004,772
Total assets
Current liabilities:
LIABILITIES AND STOCKHOLDERS’ EQUITY
Accounts payable and accrued liabilities
Short-term contingent consideration
Total current liabilities
Noncurrent liabilities:
Long-term convertible debt, net
Long-term contingent consideration
Other long-term liabilities
Total liabilities
Stockholders’ equity:
Common stock, $0.001 par value: 500,000,000 shares authorized; 186,250,719 and 183,912,514 shares issued
and outstanding, respectively
Additional paid-in capital
Company common stock held by the Nonqualified Deferred Compensation Plan
Accumulated other comprehensive income (loss)
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
(1)
Certain December 31, 2021 balances have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
The accompanying notes are an integral part of these Consolidated Financial Statements.
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BIOMARIN PHARMACEUTICAL INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
Years Ended December 31, 2022, 2021 and 2020
(In thousands of U.S. Dollars, except per share amounts)
REVENUES:
Net product revenues
Royalty and other revenues
Total revenues
OPERATING EXPENSES:
Cost of sales
Research and development
Selling, general and administrative
Intangible asset amortization and contingent consideration
Gain on sale of nonfinancial assets, net
Total operating expenses
INCOME (LOSS) FROM OPERATIONS
Interest income
Interest expense
Other income (expense), net
INCOME (LOSS) BEFORE INCOME TAXES
Provision for (benefit from) income taxes
NET INCOME (LOSS)
EARNINGS (LOSS) PER SHARE, BASIC
EARNINGS (LOSS) PER SHARE, DILUTED
Weighted average common shares outstanding, basic
Weighted average common shares outstanding, diluted
$
$
$
$
2022
2021
2020
(1)
2,042,025 $
54,014
2,096,039
1,783,498 $
62,777
1,846,275
483,669
649,606
854,009
67,193
(108,000)
1,946,477
149,562
18,034
(15,970)
(2,050)
149,576
8,015
141,561 $
0.76 $
0.75 $
185,266
188,963
470,515
628,793
759,375
69,933
—
1,928,616
(82,341)
10,482
(15,337)
11,846
(75,350)
(11,270)
(64,080) $
(0.35) $
(0.35) $
182,852
182,852
1,805,861
54,594
1,860,455
524,272
628,116
737,669
66,658
(52,820)
1,903,895
(43,440)
16,610
(29,309)
7,142
(48,997)
(903,026)
854,029
4.72
4.50
180,804
191,678
(1)
Certain December 31, 2020 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
The accompanying notes are an integral part of these Consolidated Financial Statements.
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BIOMARIN PHARMACEUTICAL INC.
CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
Years Ended December 31, 2022, 2021 and 2020
(In thousands of U.S. Dollars)
NET INCOME (LOSS)
OTHER COMPREHENSIVE INCOME (LOSS):
Available-for-sale debt securities:
Unrealized holding gain (loss) arising during the period, net
of tax impact of $3,247, $1,596 and $(227), respectively
Less: reclassifications to net income (loss), net of tax impact of
$0, $0 and $(127), respectively
Net change in unrealized holding gain (loss), net of tax
Cash flow hedges:
Unrealized holding gain (loss) arising during the period, net of tax impact of $0 for all
periods presented
Less: reclassifications to net income (loss), net of tax impact of $0 for all periods
presented
Net change in unrealized holding gain (loss), net of tax
2022
2021
2020
(1)
$
141,561 $
(64,080) $
854,029
(10,720)
—
(10,720)
29,045
36,624
(7,579)
(5,262)
—
(5,262)
34,379
(1,454)
35,833
749
425
324
(23,462)
13,180
(36,642)
15
(36,303)
817,726
Other
OTHER COMPREHENSIVE INCOME (LOSS), NET OF TAX
COMPREHENSIVE INCOME (LOSS)
—
(18,299)
123,262 $
—
30,571
(33,509) $
$
(1)
December 31, 2020 Net Income has been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these Consolidated
Financial Statements for details.
The accompanying notes are an integral part of these Consolidated Financial Statements.
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BIOMARIN PHARMACEUTICAL INC.
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
Years Ended December 31, 2022, 2021 and 2020
(In thousands of U.S. Dollars and share amounts in thousands)
Shares of Common Stock, beginning balances
Issuances under equity incentive plans
Repurchase of common stock
Shares of Common Stock, ending balances
Total stockholders' equity, beginning balances
Adjustment related to correction of immaterial error
(1)
Adjusted beginning balance
Common stock:
Beginning balances
Issuances under equity incentive plans, net of tax
Ending balances
Additional paid-in capital:
Beginning balances
Issuances under equity incentive plans, net of tax
Stock-based compensation
Repurchase of common stock
Change in Common stock held by the NQDC
Ending balances
Treasury stock:
Beginning balances
Purchase of treasury stock
Retirement of treasury stock
Ending balance
Company common stock held by the NQDC:
Beginning balances
Change in Common stock held by the NQDC
Ending balances
Accumulated other comprehensive income (loss):
Beginning balances
Other comprehensive income (loss)
Ending balances
Accumulated deficit:
Beginning balances
Adjustment related to correction of immaterial error
Adjusted beginning balance
Net income (loss)
(1)
Ending balances
2022
2021
2020
183,913
2,338
—
186,251
181,741
2,172
—
183,913
179,838
2,421
(518)
181,741
$
4,270,740 $
(5,071)
4,265,669
4,106,002 $
(5,071)
4,100,931
3,122,381
—
3,122,381
184
2
186
5,191,502
14,328
199,895
—
(830)
5,404,895
—
—
—
—
(9,689)
830
(8,859)
14,432
(18,299)
(3,867)
182
2
184
4,993,407
3,389
194,856
—
(150)
5,191,502
—
—
—
—
(9,839)
150
(9,689)
(16,139)
30,571
14,432
180
2
182
4,832,707
27,275
183,547
(50,000)
(122)
4,993,407
—
(50,000)
50,000
—
(9,961)
122
(9,839)
20,164
(36,303)
(16,139)
(925,689)
(5,071)
(930,760)
141,561
(789,199)
4,603,156 $
(861,609)
(5,071)
(866,680)
(64,080)
(930,760)
4,265,669 $
(1,720,709)
—
(1,720,709)
854,029
(866,680)
4,100,931
Total stockholders' equity, ending balances
$
(1)
The years ended December 31, 2021 and 2020 have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to
these Consolidated Financial Statements for details.
The accompanying notes are an integral part of these Consolidated Financial Statements.
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BIOMARIN PHARMACEUTICAL INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
Years Ended December 31, 2022, 2021 and 2020
(In thousands of U.S. dollars)
CASH FLOWS FROM OPERATING ACTIVITIES:
Net income (loss)
Adjustments to reconcile net income (loss) to net cash provided by operating activities:
2022
2021
2020
(1)
$
141,561 $
(64,080) $
854,029
Depreciation and amortization
Non-cash interest expense
Amortization of premium on investments
Stock-based compensation
Gain on sale of nonfinancial assets, net
Inventory reserves, net of stock-based compensation
Deferred income taxes
Unrealized foreign exchange loss (gain)
Non-cash changes in the fair value of contingent consideration
Other
Changes in operating assets and liabilities:
Accounts receivable, net
Inventory
Other current assets
Other assets
Accounts payable and other short-term liabilities
Other long-term liabilities
Net cash provided by operating activities
CASH FLOWS FROM INVESTING ACTIVITIES:
Purchases of property, plant and equipment
Maturities and sales of investments
Purchases of investments
Proceeds from sale of nonfinancial assets
Purchase of intangible assets
Investment in convertible note
Other
Net cash used in investing activities
CASH FLOWS FROM FINANCING ACTIVITIES:
Proceeds from exercises of awards under equity incentive plans
Taxes paid related to net share settlement of equity awards
Repurchase of common stock
Proceeds from convertible senior subordinated note offering, net
Repayments of convertible debt
Payments of contingent consideration
Principal repayments of financing leases
Other
Net cash provided by (used in) financing activities
Effect of exchange rate changes on cash
NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS
Cash and cash equivalents:
Beginning of period
End of period
SUPPLEMENTAL CASH FLOW DISCLOSURES:
Cash paid for interest
Cash paid for income taxes
SUPPLEMENTAL CASH FLOW DISCLOSURES FOR NON-CASH INVESTING AND FINANCING
ACTIVITIES:
Decrease in accounts payable and accrued liabilities related to fixed assets
Increase (decrease) in accounts payable and accrued liabilities related to intangible assets
101,969
4,117
3,043
196,308
(108,000)
—
(52,087)
(14,287)
1,704
(2,043)
(82,033)
(68,264)
7,822
(19,859)
59,018
6,933
175,902
(120,959)
619,995
(611,809)
103,325
(10,581)
—
—
(20,029)
69,333
(54,283)
—
—
—
(31,095)
(2,605)
—
(18,650)
32
137,255
108,039
4,146
5,155
197,263
—
—
(15,608)
(1,810)
8,026
(2,629)
65,574
(35,060)
29,760
(6,593)
15,689
(3,336)
304,536
(95,578)
691,049
(937,143)
—
(23,647)
—
(994)
(366,313)
49,194
(45,805)
—
—
—
—
(3,039)
(398)
(48)
(57)
(61,882)
$
$
$
$
$
587,276
724,531 $
10,281 $
54,372 $
649,158
587,276 $
10,395 $
18,153 $
(1,482) $
742 $
(4,749) $
9,428 $
105,172
16,511
567
189,711
(52,820)
75,609
(889,993)
8,011
4,500
(997)
(59,035)
(61,151)
18,312
(29,007)
(87,025)
(7,029)
85,365
(114,312)
555,834
(529,663)
67,159
(23,207)
(8,709)
(723)
(53,621)
71,913
(44,638)
(50,000)
585,752
(374,991)
—
(6,918)
—
181,118
(1,150)
211,712
437,446
649,158
12,178
8,977
(5,184)
(292)
(1)
Certain December 31, 2020 balances have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these Consolidated Financial
Statements for details.
The accompanying notes are an integral part of these Consolidated Financial Statements.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(1) BUSINESS OVERVIEW AND SIGNIFICANT ACCOUNTING POLICIES
Nature of Operations
Founded in 1997, BioMarin Pharmaceutical Inc. (the Company or BioMarin) is a global biotechnology company dedicated to transforming lives
through genetic discovery. The Company develops and commercializes targeted therapies that address the root cause of genetic conditions. The Company's
robust research and development capabilities have resulted in multiple innovative commercial therapies for patients with rare genetic disorders. The
Company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a
significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing
treatment options. ROCTAVIAN (formerly known as valoctocogene roxaparvovec) was granted conditional marketing approval in the European Union (EU)
on August 24, 2022.
Basis of Presentation
These Consolidated Financial Statements have been prepared pursuant to United States generally accepted accounting principles (U.S. GAAP)
and the rules and regulations of the Securities and Exchange Commission (the SEC) for Annual Reports on Form 10-K and include the accounts of BioMarin
and its wholly owned subsidiaries. All intercompany transactions have been eliminated. Management performed an evaluation of the Company’s activities
through the date of filing of this Annual Report on Form 10-K, and has concluded that there were no subsequent events or transactions that occurred
subsequent to the balance sheet date and prior to the filing of this Annual Report on Form 10-K.
Correction of Immaterial Error
During the third quarter of 2022, the Company became aware of an unrecorded amount due to a third party following the January 2020 sale of the
worldwide rights of FIRDAPSE, the Company's commercial product for the treatment of Lambert-Eaton myasthenic syndrome. The Company evaluated the
materiality of the previously described error from a qualitative and quantitative perspective. Based on such evaluation, the Company concluded that the error
was not material to any individual current or prior period, nor did it have an effect on the Company’s trend of financial results, taking into account the
requirements of the SEC Staff Accounting Bulletin No. 108, Considering the Effects of Prior Year Misstatements when Quantifying Misstatements in Current
Year Financial Statements. Although the effect of the error was not material to the current or previously issued financial statements, the Company has
corrected the accompanying Consolidated Balance Sheets, Statement of Operations, Statement of Comprehensive Income and Statements of Stockholders
Equity. As a result, the correction decreased 2020 Net Income and increased the 2020 Accumulated Deficit balance by $5.1 million. Consequently, this had
the following impact on certain December 31, 2021 balances: an increase to Accounts Payable and Accrued Liabilities of $6.7 million, a decrease to Total
Stockholders’ Equity of $5.1 million, an increase to Deferred Tax Assets of $1.1 million, an increase to Other Assets of $0.4 million and a decrease to Other
Long-term Liabilities of $0.1 million.
Use of Estimates
U.S. GAAP requires management to make estimates and assumptions that affect amounts reported on the Company’s Consolidated Financial
Statements and accompanying disclosures. Although these estimates are based on management’s best knowledge of current events and actions that the
Company may undertake in the future, actual results may be different from those estimates. The Consolidated Financial Statements reflect all adjustments of
a normal, recurring nature that are, in the opinion of management, necessary for a fair presentation of results.
Significant Accounting Policies
Cash and Cash Equivalents
The Company treats highly liquid investments, readily convertible to cash, with original maturities of three months or less on the purchase date as
cash equivalents.
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Marketable and Non-Marketable Securities
Marketable Securities
The Company determines the appropriate classification of its investments in debt and equity securities at the time of purchase and reevaluates
such designations at each reporting period. The Company classifies its debt and equity securities with original maturities greater than three months when
purchased as either short-term or long-term investments based on each instrument’s underlying contractual maturity date and its availability for use in
current operations.
All marketable securities are classified as available-for-sale. Available-for-sale debt securities are measured and recorded at fair market value with
unrealized gains and losses included in Accumulated Other Comprehensive Income (AOCI) on the Company’s Consolidated Balance Sheets, with the
exception of any declines in fair value below the cost basis that are a result of a credit loss, which, if any, are reported in Other Income (Expense), Net in the
current period through an allowance for credit losses. Impairment assessments are made at the individual security level each reporting period. When the fair
value of an investment is less than its cost at the balance sheet date, a determination is made as to whether the impairment is related to a credit loss and, if
so, an impairment loss is recognized in earnings equal to the difference between the investment’s amortized cost and fair value at such date.
Non-Marketable Equity Securities
The Company records investments in equity securities, other than equity method investments, at fair market value, if fair value is readily
determinable. Equity securities with no readily determinable fair values are recorded using the measurement alternative of cost adjusted for observable price
changes in orderly transactions for identical or similar investments of the same issuer less impairment, if any. Investments in equity securities are recorded in
Other Assets on the Company's Consolidated Balance Sheets. Unrealized gains and losses are reported in Other Income (Expense), Net. The Company
regularly reviews its non-marketable equity securities for indicators of impairment.
Inventory
Commercial Inventory
The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method.
The Company analyzes its inventory levels quarterly for obsolescence and, if required, adjusts inventory to its net realizable value if the cost basis of
inventory is in excess of its expected net realizable value, or for quantities in excess of expected demand. If the Company determines cost exceeds its net
realizable value, the resulting adjustments are recognized as Cost of Sales in the Consolidated Statements of Operations.
Inventory Produced Prior to Regulatory Approval
When future commercialization for a product candidate is considered probable and management believes that material uncertainties related to the
ultimate regulatory approval have been significantly reduced and the Company expects to realize economic benefit in the future, the Company capitalizes
pre-launch or pre-qualification manufacturing costs prior to regulatory approval. For inventories that are capitalized in preparation of product launch, a
number of factors are taken into consideration based on information available at the time, including the product candidate’s current status in the drug
development and regulatory approval process, results from the related pivotal clinical trial, results from meetings with the relevant regulatory authorities prior
to the filing of regulatory applications, historical experience, as well as potential impediments to the approval process such as product safety or efficacy, as
well as commercialization and market trends. If additional requirements are subsequently presented by the regulatory authorities, prior to their final decision
thus extending anticipated regulatory approval timelines resulting in expiration of the product prior to revised demand forecasts, the pre-launch inventory
costs are expensed to Cost of Sales. If the marketing application is ultimately rejected by the applicable regulators and the pre-launch inventory cannot be
sold for commercial use, the pre-launch inventory costs are expensed to Research and Development (R&D).
Property, Plant and Equipment
Property, plant and equipment are stated at historical cost net of accumulated depreciation. Depreciation is computed using the straight-line method
over the related estimated useful lives, as presented in the table below. Significant additions and improvements are capitalized, whereas repairs and
maintenance are expensed as incurred. Depreciation of property, plant and equipment are included in Cost of Sales, R&D and Selling, General and
Administrative (SG&A), as appropriate, in the Consolidated
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Statements of Operations. Property and equipment purchased for specific R&D projects with no alternative future uses are expensed as incurred and
recorded to R&D in the Consolidated Statements of Operations.
Leasehold improvements
Building and improvements
Manufacturing and laboratory equipment
Computer hardware and software
Office furniture and equipment
Land improvements
Land
Construction-in-progress
Leases
Shorter of life of asset or lease term
20 to 50 years
5 to 15 years
3 to 7 years
5 years
10 to 20 years
Not applicable
Not applicable
The Company's lease portfolio primarily consists of leases for properties and equipment for administrative, manufacturing and R&D activities. The
Company determines if an arrangement is a lease at contract inception. For leases where the Company is the lessee, Right of Use (ROU) assets represent
the Company’s right to use the underlying asset for the term of the lease and the lease liabilities represent the lease payment obligation. ROU assets and
lease liabilities are recognized at the lease commencement date based on the present value of the future lease payments over the lease term. The Company
uses its incremental borrowing rate based on the information available at the commencement date of the underlying lease arrangement to determine the
present value of lease payments. The ROU asset also includes any prepaid lease payments and any lease incentives received. The lease term to calculate
the ROU asset and related lease liability includes options to extend or terminate the lease when it is reasonably certain that the Company will exercise the
option. The Company’s lease agreements generally do not contain any material variable lease payments, residual value guarantees or restrictive covenants.
Lease expense for operating leases is recognized on a straight-line basis over the lease term as an operating expense while expense for financing
leases is recognized as depreciation expense and interest expense using the accelerated interest method of recognition. When an arrangement requires
payments for lease and non-lease components, the Company has elected to account for lease and non-lease components separately. Lease expense for
leases with a term of twelve months or less is recognized on a straight-line basis and are not included in the recognized ROU assets and lease liabilities.
Goodwill and Intangible Assets
The Company records goodwill in a business combination when the total consideration exceeds the fair value of the assets acquired.
Intangible assets with indefinite useful lives are related to purchased in-process research and development (IPR&D) projects and are measured at
their respective fair values as of the acquisition date. Intangible assets related to IPR&D projects are considered to be indefinite-lived until the completion or
abandonment of the associated R&D efforts. If and when development is complete, which generally occurs if and when regulatory approval to market a
product is obtained, the associated assets are considered finite-lived and are amortized using the straight-line method based on their respective estimated
useful lives at that point in time. The amortization of these intangible assets is included in Intangible Asset Amortization and Contingent Consideration in the
Consolidated Statements of Operations.
Impairment
The Company assesses goodwill and indefinite-lived intangible assets for impairment annually in the fourth quarter, or more frequently as warranted
by events or changes in circumstances that indicate that the carrying amount may not be recoverable.
Goodwill is assessed for impairment by comparing the fair value of the Company’s reporting unit with its carrying amount. If the carrying value of the
reporting unit exceeds its fair value, an impairment loss equal to the difference would be recorded.
Indefinite-lived intangible assets are assessed for impairment first by performing a qualitative assessment. If the qualitative assessment indicates
that it is more likely than not that the fair value of an indefinite-lived intangible asset is less than its carrying amount, then the Company will perform a
quantitative assessment and record an impairment loss.
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Long-lived Asset Impairment
The Company’s long-lived assets consist of property, plant and equipment, leased ROU assets and finite-lived intangible assets, which includes
costs associated with technology transfer to qualify a manufacturing facility for commercial production. Should there be an indication of impairment, the
Company tests for recoverability by comparing the estimated undiscounted future cash flows expected to result from the use of the asset or asset group and
its eventual disposition to the carrying amount of the asset or asset group. Any excess of the carrying value of the asset or asset group over its estimated fair
value is recognized as an impairment loss. Impairment charges related to property, plant or equipment that are not material are recorded to depreciation
expense and presented in SG&A in the Consolidated Statements of Operations. Impairment charges for finite-lived intangible assets associated with
technology transfer costs that are not material are recorded to Cost of Sales in the Consolidated Statements of Operations. Impairment charges related to all
other finite-lived intangible assets that are not material are recorded to Intangible Asset Amortization and Contingent Consideration in the Consolidated
Statements of Operations.
Capitalized Software
The Company capitalizes software development costs associated with internal use software, including external direct costs of materials and
services and payroll costs for employees devoting time to a software project. Costs incurred during the preliminary project stage, as well as costs for
maintenance and training, are expensed as incurred.
Revenue Recognition
The Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration
which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for contracts with customers, the
Company performs the following five steps:
(i)
(ii)
(iii)
(iv)
(v)
identification of the promised goods or services in the contract;
determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of
the contract;
measurement of the transaction price, including the constraint on variable consideration;
allocation of the transaction price to the performance obligations based on estimated selling prices; and
recognition of revenue when (or as) the Company satisfies each performance obligation. A performance obligation is a promise in a
contract to transfer a distinct good or service to the customer and is the unit of account.
Net Product Revenues
In the U.S., the Company’s commercial products, except for PALYNZIQ and ALDURAZYME, are generally sold to specialty pharmacies or end-
users, such as hospitals, which act as retailers. PALYNZIQ is distributed in the U.S. through certain certified specialty pharmacies under the PALYNZIQ Risk
Evaluation and Mitigation Strategy (REMS) and ALDURAZYME is marketed world-wide by Sanofi. Outside the U.S., the Company’s commercial products
are sold to its authorized distributors or directly to government purchasers or hospitals, which act as the end-users. Revenues from product sales are
recognized when the customer obtains control of the Company’s product, which occurs at a point in time, typically upon shipment to the customer. The
Company's payment terms vary by customer, jurisdiction or, in some instances, by product. With the exception of Sanofi and certain outcomes-based
contracts, most of the Company's payment terms are based on customary commercial terms and are generally less than one year after the customer obtains
control. The Company does not adjust revenue for the effects of a significant financing component for contracts if the period between the transfer of control
and corresponding payment is expected to be one year or less. Amounts collected from customers and remitted to governmental authorities, which primarily
consist of value-added taxes related to product sales in foreign jurisdictions, are presented on a net basis on the Company’s Consolidated Statements of
Operations, in that taxes billed to customers are not included as a component of Net Product Revenues.
For ALDURAZYME revenues, the Company receives a payment ranging from 39.5% to 50% on worldwide net ALDURAZYME sales by Sanofi
depending on sales volume, which is included in Net Product Revenues on the Company’s Consolidated Statements of Operations. The Company
recognizes its best estimate of the revenue it expects to earn when the product is released and control is transferred to Sanofi. The Company records
ALDURAZYME net product revenues based on the estimated variable consideration payable when the product is sold through by Sanofi. Actual amounts of
consideration ultimately received may differ from the Company’s estimates. Differences between the estimated variable consideration to be received from
Sanofi and actual payments received are not expected to be material. If actual results vary from the Company’s estimates, the Company will make
adjustments, which would affect Net Product Revenues and earnings in the period such variances become known.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Table of Content
Revenue Reserves
Revenues from product sales are recorded at the net sales price (transaction price), which includes estimates of variable consideration for which
reserves are established and which result from government and commercial rebates, sales returns, and other incentives that are offered within contracts
between the Company and its customers, such as specialty pharmacies, hospitals, authorized distributors and government purchasers. Such variable
consideration includes rebates, chargebacks, sales returns and other incentives. These reserves are based on the amounts earned or to be claimed on the
related sales and are classified as reductions of accounts receivable (if the amount is payable to the customer) or a current liability (if the amount is payable
to a party other than a customer). Where appropriate, these estimates take into consideration a range of possible outcomes that are probability-weighted for
relevant factors such as the Company’s historical experience, current contractual and statutory requirements, specific known market events and trends,
patient outcomes, industry data and forecasted customer buying and payment patterns. Overall, these reserves reflect the Company’s best estimates of the
amount of consideration to which it is entitled based on the terms of the contract. The amount of variable consideration that is included in the transaction
price may be constrained and is included in the net sales price only to the extent that it is probable that a significant reversal in the amount of the cumulative
revenue recognized will not occur in a future period. Actual amounts of consideration ultimately received may differ from the Company’s estimates, however
the Company does not expect any such difference to be material. If actual results in the future vary from the Company’s estimates, the Company will adjust
its estimates, which would affect net product revenue and earnings in the period such variances become known.
Government and Commercial Rebates: The Company records reserves for rebates payable under government programs, such as Medicaid, and
commercial arrangements, such as managed care rebates, as a reduction of revenue at the time product revenues are recorded. The Company’s reserve
calculations require estimates, including estimates of customer mix and patient outcomes, to determine which sales will be subject to rebates and the
amount of such rebates. The Company updates its estimates and assumptions on a quarterly basis and records any necessary adjustments to its reserves.
Sales Returns: The Company records allowances for product returns, if appropriate, as a reduction of revenue at the time product sales are
recorded. Several factors are considered in determining whether an allowance for product returns is required, including market exclusivity of the products
based on their orphan drug status, the patient population, the customers’ limited return rights and the Company’s historical experience with returns. Because
of the pricing of the Company’s commercial products, the limited number of patients and the customers’ limited return rights, most customers and retailers
carry a limited inventory. The Company relies on historical return rates to estimate a reserve for returns. Based on these factors and the fact that the
Company has not experienced significant product returns to date, return allowances are not material.
Other Incentives: Other incentives include fees paid to the Company’s distributors and discounts for prompt payment. The Company also offers a
branded co-pay assistance program for eligible patients with commercial insurance in the U.S. who are on an eligible BioMarin product. The branded co-pay
assistance programs assist commercially insured patients who have coverage for an eligible BioMarin product and are intended to reduce each participating
patient’s portion of the financial responsibility of the purchase price up to a specified dollar amount of assistance. The Company records fees paid to
distributors, cash discounts and amounts paid under the brand specific co-pay assistance program for each patient as a reduction of revenue.
Royalty and Other Revenues
Royalties: For arrangements that include the receipt of sales-based royalties, including milestone payments based on the level of sales when the
license is deemed to be the predominant item to which the royalties relate, the Company recognizes revenue at the later of (a) when the related sales occur,
or (b) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).
Licenses of intellectual property: If the license to the Company’s intellectual property is determined to be distinct from the other performance
obligations identified in the arrangement, the Company recognizes revenues from non-refundable, up-front fees allocated to the license when the license is
transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company
uses judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over
time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from non-refundable, up-front
fees. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue
recognition.
Milestone payments: At the inception of each arrangement that includes developmental, regulatory or commercial milestone payments, the
Company evaluates whether achieving the milestones is considered probable and estimates the amount to be included in the transaction price using the
most likely amount method. If it is probable that a significant revenue reversal would not occur, the value of the associated milestone (such as a regulatory
submission by the Company) is included in the transaction price. Milestone payments that are not within the control of the Company, such as approvals from
regulators or where
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
attainment of the specified event is dependent on the development activities of a third party, are not considered probable of being achieved until those
approvals are received or the specified event occurs. Revenue is recognized from the satisfaction of performance obligations in the amount billable to the
customer.
Research and Development
R&D costs are generally expensed as incurred. These expenses include contract R&D services provided by third parties, preclinical and clinical
studies, raw materials costs associated with manufacturing clinical product, quality control and assurance, other R&D activities, facilities and regulatory costs
and R&D-related personnel costs including salaries, benefits and stock-based compensation. Upfront and milestone payments made to third parties in
connection with licensed intellectual property, which does not have an alternative future use or does not reach technological feasibility, are expensed as
incurred up to the point of regulatory approval.
Advertising Expenses
The costs of advertising are presented in SG&A in the Consolidated Statements of Operations and are expensed as incurred. Advertising expenses
were $25.2 million, $30.2 million and $29.3 million in 2022, 2021 and 2020, respectively.
Earnings (Loss) Per Common Share
Basic earnings (loss) per share is calculated by dividing Net Income (Loss) by the weighted average shares of common stock outstanding during
the period. Diluted earnings (loss) per share reflects the potential dilution that would occur if securities or other contracts to issue common stock were
exercised or converted into common stock; however, potential common equivalent shares are excluded if their effect is anti-dilutive.
Stock-Based Compensation
The Company has equity incentive plans under which various types of equity-based awards may be granted to employees. Stock-based
compensation expense is recognized on a straight-line basis over the requisite service period, which is generally the vesting period required to obtain full
vesting, and is classified as Cost of Sales, R&D or SG&A, as appropriate, in the Consolidated Statements of Operations. The Company accounts for
forfeitures as they occur.
Restricted Stock Units
The fair value of restricted stock units (RSUs) with service-based vesting conditions and RSUs with performance conditions is determined to be the
fair market value of the Company’s underlying common stock on the date of grant. The stock-based compensation expense for RSUs with service-based
vesting is recognized over the period during which the vesting restrictions lapse. Stock-based compensation expense for RSUs with performance conditions
is recognized beginning in the period the Company determines it is probable that the performance condition will be achieved. Management expectations
related to the achievement of performance goals associated with RSUs with performance conditions are assessed regularly to determine whether such
grants are expected to vest. The fair value for RSUs with market conditions is estimated using the Monte Carlo valuation model, utilizing expected volatility
rates derived from those of the Company and the members of the referenced peer group. Related stock-based compensation is recognized, beginning on
the grant date, on a straight-line basis regardless of whether the market condition is met unless the required service is not performed.
Stock Options and Purchase Rights
The fair value of each stock option award and purchase rights under the Company’s Employee Stock Purchase Plan (ESPP) are estimated on the
date of grant using the Black-Scholes valuation model and the following assumptions: expected term, expected volatility, risk-free interest rate and expected
dividend yield. The dividend yield reflects that the Company has not paid any cash dividends since inception and does not intend to pay any cash dividends
in the foreseeable future. The expected term of stock options is based on observed historical exercise patterns. In estimating the life of stock options, the
Company has identified two employee groups with distinctly different historical exercise patterns: executive and non-executive. The executive employee
group has a history of holding stock options for longer periods than non-executive employees. The expected term of purchase rights for ESPP is based on
each tranche of an offering period, which is four tranches in a twenty-four-month period.
The determination of the fair value of stock-based payment awards using an option-pricing model is affected by the Company’s stock price and may
use assumptions regarding a number of complex and subjective variables.
96
BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Table of Content
Income Taxes
The Company calculates and provides for income taxes in each of the tax jurisdictions in which it operates. Deferred tax assets and liabilities,
measured using enacted tax rates, are recognized for the future tax consequences of temporary differences between the tax and financial statement basis of
assets and liabilities. A valuation allowance reduces the deferred tax assets to the amount that is more likely than not to be realized. The Company
establishes liabilities or reduces assets for uncertain tax positions when the Company believes certain tax positions are not more likely than not of being
sustained if challenged. Each quarter, the Company evaluates these uncertain tax positions and adjusts the related tax assets and liabilities in light of
changing facts and circumstances.
The Company uses financial projections to support its net deferred tax assets, which contain significant assumptions and estimates of future
operations. If such assumptions were to differ significantly, it may have a material impact on the Company’s ability to realize its deferred tax assets. At the
end of each period, the Company will reassess the ability to realize its deferred tax benefits. If it is more likely than not that the Company would not realize
the deferred tax benefits, a valuation allowance may need to be established against all or a portion of the deferred tax assets, which will result in a charge to
tax expense.
Foreign Currency
For the Company and its subsidiaries, the functional currency has been determined to be the U.S. Dollar (USD). Assets and liabilities denominated
in foreign currency are remeasured at period-end exchange rates for monetary assets. Non-monetary assets and liabilities denominated in foreign currencies
are remeasured at historical rates. Foreign currency transaction losses resulting from remeasurement recognized in SG&A in the Consolidated Statements
of Operations totaled $11.4 million, $11.7 million and $9.9 million in 2022, 2021 and 2020, respectively.
Derivatives and Hedging Activities
The Company uses foreign currency exchange forward contracts (forward contracts) to hedge certain operational exposures resulting from potential
changes in foreign currency exchange rates. Such exposures result from portions of the Company’s forecasted revenues and operating expenses being
denominated in currencies other than the USD, primarily the Euro. The Company designates certain of these forward contracts as hedging instruments and
also enters into forward contracts that are considered to be economic hedges that are not designated as hedging instruments. Whether designated or
undesignated, these forward contracts protect against the reduction in value of forecasted foreign currency cash flows resulting from gross product
revenues, operating expenses and asset or liability positions designated in currencies other than the USD. To receive hedge accounting treatment, cash flow
hedges must be highly effective in offsetting changes to expected future cash flows on hedged transactions. The Company does not hold or issue derivative
instruments for trading or speculative purposes.
The Company is exposed to counterparty credit risk on its derivatives. The Company has established and maintains strict counterparty credit
guidelines and enters into hedging agreements with financial institutions that are investment grade or better to minimize the Company’s exposure to potential
defaults. The Company is not required to pledge collateral under these agreements.
The Company accounts for its derivative instruments as either assets or liabilities on its Consolidated Balance Sheets and measures them at fair
value, which is estimated using current exchange rates and interest rates and takes into consideration the current creditworthiness of the counterparties or
the Company, as applicable. For derivatives designated as hedging instruments, the entire change in the fair value of qualifying derivative instruments is
recorded in AOCI and amounts deferred in AOCI are reclassified to earnings in the same line item in which the earnings effect of the hedged item is
reported. Derivatives not designated as hedging instruments are adjusted to fair value through earnings in SG&A in the Consolidated Statements of
Operations.
Fair Value of Financial Instruments
The Company applies fair value accounting for all financial assets and liabilities and non-financial assets and liabilities that are recognized or
disclosed at fair value in the financial statements on a recurring basis. The Company defines fair value as the price that would be received from selling an
asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. When determining the fair value
measurements for assets and liabilities that are required to be recorded at fair value, the Company considers the principal or most advantageous market in
which the Company would transact and the market-based risk measurements or assumptions that market participants would use to price the asset or liability,
such as risks inherent in valuation techniques, transfer restrictions and credit risk. When estimating fair value, depending on the nature and complexity of the
asset or liability, the Company may use the following techniques:
•
•
Income approach, which is based on the present value of a future stream of net cash flows
Market approach, which is based on market prices and other information from market transactions involving identical or comparable assets
or liabilities.
97
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The Company’s fair value methodologies depend on the following types of inputs:
•
•
•
Quoted prices for identical assets or liabilities in active markets (Level 1 inputs)
Quoted prices for similar assets or liabilities in active markets, or quoted prices for identical or similar assets or liabilities that are not
active, or inputs other than quoted process that are directly or indirectly observable, or inputs that are derived principally from, or
corroborated by, observable market data by correlation or other means (Level 2 inputs)
Unobservable inputs that reflect estimates and assumptions (Level 3 inputs)
The Company’s Level 2 instruments are valued using third-party pricing sources. The pricing services utilize industry standard valuation models,
including both income and market-based approaches, for which all significant inputs are observable, either directly or indirectly, to estimate fair value. These
inputs include reported trades of and broker/dealer quotes on the same or similar securities, issuer credit spreads, benchmark securities, prepayment/default
projections based on historical data and other observable inputs. The Company validates the prices provided by its third-party pricing services by
understanding the models used, obtaining market values from other pricing sources, analyzing pricing data in certain instances and confirming those
securities traded in active markets.
The Company’s Level 3 financial assets and liabilities include acquired intangible assets and contingent consideration resulting from business
acquisitions. The estimated fair value of acquired finite-lived and indefinite-lived intangible assets and contingent consideration are measured by applying a
probability-based income approach utilizing an appropriate discount rate as of the acquisition date. Key assumptions used by management to estimate the
fair value of contingent consideration include estimated probabilities, the estimated timing of when a milestone may be attained and assumed discount
periods and rates. Changes in the fair value of contingent consideration can result from changes to one or more inputs, including the estimated probability
with respect to regulatory approval, changes in the assumed timing of when milestones are likely to be achieved and changes in assumed discount periods
and rates. Contingent consideration is remeasured on a recurring basis and resulting changes in the fair value, due to the revision of key assumptions, are
recorded in Intangible Asset Amortization and Contingent Consideration on the Company’s Consolidated Statements of Operations.
See Notes 2, 7, 8, 10 and 17 to these Consolidated Financial Statements for further information on the nature of these financial instruments.
Segment Information
The Company currently operates in one segment focused on the development and commercialization of innovative therapies for people with serious
and life-threatening rare diseases and medical conditions. A single management team reports to the chief operating decision maker who comprehensively
manages the entire business. All products are included in one operating segment because the majority of the Company’s products have similar economic
and other characteristics, including the nature of the products and production processes, type of customers, distribution methods and regulatory
environment. The Company is not organized by market and is managed and operated as one business. The Company does not operate any separate lines
of business or separate business entities with respect to its products. Accordingly, the Company does not accumulate discrete financial information with
respect to separate products, other than revenues, cost of sales and certain other operating expenses.
Recent Accounting Pronouncements
There have been no new accounting pronouncements adopted by the Company or new accounting pronouncements issued by the Financial
Accounting Standards Board (FASB) during 2022 that the Company believes are of significance or potential significance to the Company.
98
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(2) FINANCIAL INSTRUMENTS
The following tables show the Company’s cash, cash equivalents and available-for-sale securities by significant investment category as of
December 31, 2022 and 2021, respectively:
Amortized Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Aggregate Fair
Value
Cash and Cash
Equivalents
Short-term
Marketable
(1)
Securities
Long-term
Marketable
(2)
Securities
December 31, 2022
$
463,248 $
— $
— $
463,248 $
463,248 $
— $
248,933
504,984
312,720
48,103
—
34
45
11
(3,771)
(22)
308,994
48,092
—
248,933
248,933
—
(11,541)
493,477
1,881
299,153
192,443
—
10,469
—
261,283
724,531 $
229,846
37,623
384
567,006
567,006 $
79,148
—
62,244
333,835
333,835
Total
$
63,151
1,177,891
1,641,139 $
69
159
159 $
(592)
(15,926)
(15,926) $
62,628
1,162,124
1,625,372 $
Amortized Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Aggregate Fair
Value
Cash and Cash
Equivalents
Short-term
Marketable
(1)
Securities
Long-term
Marketable
(2)
Securities
December 31, 2021
$
301,177 $
— $
— $
301,177 $
301,177 $
— $
285,099
584,000
224,774
68,384
56,936
3,097
1,222,290
1,523,467 $
—
386
182
—
10
141
719
719 $
—
285,099
285,099
—
(2,086)
582,300
—
200,304
381,996
(325)
—
224,631
68,384
(95)
(12)
(2,518)
(2,518) $
56,851
3,226
1,220,491
1,521,668 $
—
1,000
—
—
286,099
587,276 $
146,421
67,384
9,451
3,039
426,599
426,599 $
78,210
—
47,400
187
507,793
507,793
(1)
(2)
The Company’s short-term marketable securities mature in one year or less.
The Company’s long-term marketable securities mature between one and five years.
As of December 31, 2022, the Company had the ability and intent to hold all investments that were in an unrealized loss position until maturity. The
Company considered its intent and ability to hold the securities until recovery of amortized cost basis, the extent to which fair value is less than amortized
cost basis, conditions specifically related to the security’s industry and geography, payment structure and history and changes to the ratings (if any) in
determining that the decline in fair value compared to carrying value is not related to a credit loss.
99
Level 1:
Cash
Level 2:
Money market
instruments
Corporate debt
securities
U.S. government
agency securities
Commercial paper
Asset-backed
securities
Subtotal
Level 1:
Cash
Level 2:
Money market
instruments
Corporate debt
securities
U.S. government
agency securities
Commercial paper
Asset-backed
securities
Foreign and other
Subtotal
Total
$
—
—
—
—
Table of Content
BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The Company has certain investments in non-marketable equity securities, measured using unobservable valuation inputs and remeasured on a
nonrecurring basis, which are collectively considered strategic investments. As of December 31, 2022 and December 31, 2021, the fair value of the
Company’s strategic investments was $23.9 million and $16.5 million, respectively. These investments were recorded in Other Assets on the Company’s
Consolidated Balance Sheets.
See Note 1 to these Consolidated Financial Statements for additional discussion regarding the Company’s fair value measurements.
(3) INTANGIBLE ASSETS
Intangible Assets, Net consisted of the following:
Finite-lived intangible assets
Accumulated amortization
Net carrying value
December 31,
2022
2021
$
$
690,871 $
(352,302)
338,569 $
677,350
(288,698)
388,652
The following table summarizes the carrying value and estimated remaining life of the Company’s finite-lived intangible assets as of December 31,
2022:
Acquired intellectual property
Technology transfer
Repurchased royalty rights
License payments
Other
Total
Net Balance
240,321
86,578
6,188
5,436
46
338,569
$
$
Average Remaining
Life
5.1 years
5.4 years
0.9 years
7.7 years
0.3 years
(1)
(1)
Certain technology transfer intangible assets have not yet been placed into service. The average remaining life presented is only for those placed
into service.
As of December 31, 2022, the estimated future amortization expense associated with the Company’s finite-lived intangible assets that have been
placed into service, was as follows:
Fiscal Year
2023
2024
2025
2026
2027
Thereafter
Amount
63,688
57,413
38,136
38,136
38,136
25,746
261,255
$
$
In 2022 the Company completed the sale of a Rare Pediatric Disease Priority Review Voucher (PRV) the Company received from the Food and
Drug Administration (FDA) in connection with the U.S. approval of VOXZOGO. As a result of the PRV sale, the Company recognized a $108.0 million net
gain on sale of nonfinancial assets in the first quarter of 2022 on the Company's Consolidated Statement of Operations.
100
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(4) PROPERTY, PLANT AND EQUIPMENT
Property, Plant and Equipment, Net, consisted of the following:
Building and improvements
Manufacturing and laboratory equipment
Computer hardware and software
Land
Leasehold improvements
Furniture and equipment
Land improvements
Construction-in-progress
Accumulated depreciation
Total property, plant and equipment, net
December 31
2022
2021
$
$
819,100 $
475,663
214,829
90,786
59,532
45,762
26,455
143,384
1,875,511
(802,145)
1,073,366 $
774,923
444,182
201,382
90,418
55,279
42,976
10,132
136,743
1,756,035
(720,574)
1,035,461
Depreciation expense, net of amounts capitalized into inventory, was $38.6 million, $46.1 million and $43.0 million for the years ended
December 31, 2022, 2021 and 2020, respectively.
(5) INVENTORY
Inventory consisted of the following:
Raw materials
Work-in-process
Finished goods
Total inventory
December 31
2022
2021
$
$
131,071 $
410,656
352,356
894,083 $
80,269
415,261
281,139
776,669
101
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(6) SUPPLEMENTAL FINANCIAL STATEMENT INFORMATION
Accounts Payable and Accrued Liabilities consisted of the following:
(1)
Accounts payable and accrued operating expenses
Accrued compensation expense
Accrued rebates payable
Accrued income taxes
Accrued royalties payable
Foreign currency exchange forward contracts
Lease liability
Deferred revenue
Other
Total accounts payable and accrued liabilities
December 31,
2022
2021
$
$
231,238 $
207,573
72,654
16,213
13,306
12,601
10,375
711
8,288
572,959 $
199,678
204,446
47,987
1,213
15,215
6,263
10,464
6,956
6,043
498,265
(1)
The balance as of December 31, 2021 has been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
Reorganization Plan Costs
On October 6, 2022, the Company announced a plan to simplify its organizational design, which included a planned reduction in headcount of
approximately 120 employees (representing approximately 4% of the Company’s global workforce), most of whom were from the Company's U.S.
operations. The reduction in headcount was substantially completed as of December 31, 2022. In 2022, the Company recorded costs of $23.0 million related
to one-time termination severance and employee termination benefits within SG&A expense, of which $11.9 million has been paid as of December 31, 2022.
The Company does not expect to incur any significant incremental costs in future periods. The unpaid balance at December 31, 2022 is recorded to
Accounts Payable and Accrued Liabilities on the Consolidated Balance Sheet and is expected to be paid within the next 12 months.
Significant Revenue Rebates and Reserves for Cash Discounts
The roll forward of significant estimated accrued rebates and reserve for cash discounts for the years ended December 31, 2022, 2021 and 2020,
were as follows:
Year ended December 31, 2022:
Accrued rebates
Reserve for cash discounts
Year ended December 31, 2021:
Accrued rebates
Reserve for cash discounts
Year ended December 31, 2020:
Accrued rebates
Reserve for cash discounts
Balance at
Beginning
of Period
Provision for
Current Period
Sales
Payments
Balance at
End of
Period
47,987 $
2,013 $
140,260 $
20,351 $
(115,593) $
(18,725) $
65,526 $
1,716 $
116,691 $
16,003 $
(134,230) $
(15,706) $
57,163 $
1,889 $
113,165 $
17,191 $
(104,802) $
(17,364) $
72,654
3,639
47,987
2,013
65,526
1,716
$
$
$
$
$
$
102
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(7) FAIR VALUE MEASUREMENTS
The Company measures certain financial assets and liabilities at fair value in accordance with the policy described in Note 1 to these Consolidated
Financial Statements.
The following tables present the classification within the fair value hierarchy of financial assets and liabilities not disclosed elsewhere in these
Consolidated Financial Statements that are remeasured on a recurring basis as of December 31, 2022 and 2021. Other than the Company’s fixed-rate
convertible debt disclosed in Note 10 to these Consolidated Financial Statements, there were no financial assets or liabilities that were remeasured using a
quoted price in active markets for identical assets (Level 1) as of December 31, 2022 and 2021. Refer to Notes 2 and 8 to these Consolidated Financial
Statements for other financial assets and liabilities measured at fair value.
Assets:
Other current assets:
NQDC Plan assets
Other assets:
NQDC Plan assets
Restricted investments
Total other assets
(1)
Total assets
Liabilities:
Current liabilities:
NQDC Plan liability
Contingent consideration
Total current liabilities
Other long-term liabilities:
NQDC Plan liability
Total other long-term liabilities
Total liabilities
Fair Value Measurements as of December 31, 2022
Significant Other
Observable
Inputs
(Level 2)
Significant
Unobservable
Inputs
(Level 3)
Total
2,654 $
19,867
2,429
22,296
24,950 $
2,654 $
—
2,654
19,867
19,867
22,521 $
— $
—
—
—
— $
— $
15,925
15,925
—
—
15,925 $
2,654
19,867
2,429
22,296
24,950
2,654
15,925
18,579
19,867
19,867
38,446
$
$
$
$
103
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Assets:
Other current assets:
NQDC Plan assets
Other assets:
NQDC Plan assets
Restricted investments
Total other assets
(1)
Total assets
Liabilities:
Current liabilities:
NQDC Plan liability
Contingent consideration
Total current liabilities
Other long-term liabilities:
NQDC Plan liability
Contingent consideration
Total other long-term liabilities
Total liabilities
Fair Value Measurements as of December 31, 2021
Significant Other
Observable
Inputs
(Level 2)
Significant
Unobservable
Inputs
(Level 3)
Total
$
$
$
$
2,043 $
23,929
2,940
26,869
28,912 $
2,043 $
—
2,043
23,929
—
23,929
25,972 $
— $
—
—
—
— $
— $
48,232
48,232
—
15,167
15,167
63,399 $
2,043
23,929
2,940
26,869
28,912
2,043
48,232
50,275
23,929
15,167
39,096
89,371
(1)
The restricted investments as of December 31, 2022 and 2021 secure the Company’s irrevocable standby letters of credit obtained in connection
with certain commercial agreements.
There were no transfers between levels during the periods presented.
Liabilities measured at fair value using Level 3 inputs consisted of contingent consideration. The following tables represent a roll-forward of
contingent consideration.
Contingent consideration as of December 31, 2021
Milestone payments to Ares Trading S.A. (Merck Serono)
Changes in fair value of contingent consideration
Realized foreign exchange gain on settlement of contingent consideration
Foreign exchange remeasurement of Euro denominated contingent consideration
Contingent consideration as of December 31, 2022
$
$
63,399
(47,738)
4,399
(2,333)
(1,802)
15,925
104
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(8) DERIVATIVE INSTRUMENTS AND HEDGING STRATEGIES
The Company's forward contracts designated as hedging instruments have maturities up to 1 year, 9 months. The Company's forward contracts
that are considered to be economic hedges that are not designated as hedging instruments have maturities up to 3 months.
The following table summarizes the aggregate notional amounts for the Company’s derivatives outstanding as of the periods presented.
Forward Contracts
Derivatives designated as hedging instruments:
Sell
Purchase
Derivatives not designated as hedging instruments:
Sell
Purchase
December 31, 2022
December 31, 2021
$
$
$
$
808,635 $
177,393 $
218,903 $
6,785 $
740,667
183,256
113,257
31,068
The fair value carrying amounts of the Company’s derivatives, as classified within the fair value hierarchy, were as follows:
Balance Sheet Location
Derivatives designated as hedging instruments:
Asset Derivatives - Level 2
(1)
Other current assets
Other assets
Subtotal
Liability Derivatives - Level 2
(1)
Accounts payable and accrued liabilities
Other long-term liabilities
Subtotal
Derivatives not designated as hedging instruments:
Asset Derivatives - Level 2
(1)
Other current assets
Liability Derivatives - Level 2
(1)
Accounts payable and accrued liabilities
Total Derivatives Assets
Total Derivatives Liabilities
December 31, 2022
December 31, 2021
$
$
$
$
$
$
$
$
19,464 $
2,059
21,523 $
12,130 $
1,074
13,204 $
1,472 $
471 $
22,995 $
13,675 $
17,357
4,991
22,348
5,487
1,378
6,865
427
776
22,775
7,641
(1) Refer to Note 1 to these Consolidated Financial Statements for additional information related to the Company’s fair value measurements.
105
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The following tables summarize the impact of gains and losses from the Company's derivatives on its Consolidated Statements of Operations for
the periods presented.
Derivatives Designated as Cash Flow Hedging Instruments
Net product revenues
Operating expenses
Derivatives Not Designated as Hedging Instruments
Operating expenses
Years Ended December 31,
2022
Cash Flow Hedging
Gains (Losses)
Reclassified into
Earnings
2021
Cash Flow Hedging
Gains (Losses)
Reclassified into
Earnings
$
$
$
48,541
(11,917)
$
$
196
(1,650)
Gains (Losses)
Recognized in
Earnings
Gains (Losses)
Recognized in
Earnings
872
$
1,548
As of December 31, 2022, the Company expects to reclassify unrealized losses of $7.2 million from AOCI to earnings as the forecasted revenue
and operating expense transactions occur over the next twelve months. For additional discussion of balances in AOCI see Note 11 to these Consolidated
Financial Statements.
106
BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Table of Content
(9) LEASES
The following table presents the Company’s ROU assets and lease liabilities for the periods presented.
Lease Classification
Assets:
Operating
Financing
Total ROU assets
Liabilities:
Current:
Operating
Financing
Noncurrent:
Operating
Financing
Total lease liabilities
Classification
Other assets
Other assets
Accounts payable and accrued liabilities
Accounts payable and accrued liabilities
Other long-term liabilities
Other long-term liabilities
December 31,
2022
2021
$
$
$
$
34,935 $
6,021
40,956 $
8,088 $
2,287
26,329
184
36,888 $
38,198
8,220
46,418
8,198
2,266
31,882
1,960
44,306
Maturities of lease liabilities as of December 31, 2022 by fiscal year were as follows:
Maturity of Lease Liabilities
2023
2024
2025
2026
2027
Thereafter
Total lease payments
Less: Interest
Present value of lease liabilities
Operating
Financing
Total
$
$
9,691 $
7,586
5,960
4,978
4,341
7,211
39,767
(5,350)
34,417 $
2,341 $
123
53
6
—
—
2,523
(52)
2,471 $
12,032
7,709
6,013
4,984
4,341
7,211
42,290
(5,402)
36,888
13,962
3,339
283
17,584
Lease costs associated with payments under the Company’s leases for the periods presented were as follows:
Lease Cost
(1)
Operating
Financing:
Amortization
Interest expense
Total lease costs
Classification
Operating expenses
Operating expenses
Operating expenses
$
$
Years Ended December 31,
2022
2021
13,669 $
2,858
163
16,690 $
(1) Includes short-term leases and variable lease costs, both of which were not material in the periods presented.
107
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The following table includes the weighted average remaining lease terms and the weighted average discount rate used to calculate the present
value of the Company’s lease liabilities:
Other Information
Weighted average remaining lease term (in years):
Operating leases
Financing leases
Weighted average discount rate:
Operating leases
Financing leases
Years Ended December 31,
2022
2021
5.2
1.7
5.1 %
5.4 %
As of December 31, 2022, no leases were expected to commence that would create significant rights and obligations for the Company.
Supplemental Cash Flow Information
Cash paid for amounts included in the measurement of lease liabilities:
Cash used in operating activities:
Operating leases
Financing leases
Cash used in financing activities:
Financing leases
ROU assets obtained in exchange for lease obligations:
Operating leases
Financing leases
Years Ended December 31,
2022
2021
$
$
$
$
$
10,760 $
165 $
2,605 $
5,252 $
878 $
6.2
1.9
5.0 %
5.1 %
10,664
283
3,039
760
462
(10) DEBT
Convertible Notes
As of December 31, 2022, the Company had outstanding fixed-rate notes with varying maturities for an undiscounted aggregate principal amount of
$1.1 billion (collectively the Notes). The Notes are senior subordinated convertible obligations, and
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
interest is payable in arrears, semi-annually. The following table summarizes information regarding the Company’s convertible debt:
1.250% senior subordinated convertible notes due in May 2027 (the 2027 Notes)
Unamortized discount net of deferred offering costs
2027 Notes, net
0.599% senior subordinated convertible notes due in August 2024 (the 2024 Notes)
Unamortized discount net of deferred offering costs
2024 Notes, net
Total convertible debt, net
Fair value of fixed-rate convertible debt
2027 Notes
2024 Notes
(1)
:
Total fair value of fixed-rate convertible debt
December 31,
2022
2021
600,000 $
(8,941)
591,059
495,000
(3,040)
491,960
600,000
(10,971)
589,029
495,000
(4,952)
490,048
1,083,019 $
1,079,077
647,370 $
526,230
1,173,600 $
625,122
521,082
1,146,204
$
$
$
$
(1)
The fair value of the Company’s fixed-rate convertible debt is based on open market trades and is classified as Level 1 in the fair value hierarchy.
See Note 1 to these Consolidated Financial Statements for additional discussion of fair value measurements.
Interest expense on the Company’s fixed-rate convertible debt consisted of the following:
Coupon interest expense
Accretion of discount on convertible notes
Amortization of debt issuance costs
Total interest expense on convertible debt
2027 Notes
Years Ended December 31,
2021
2020
2022
$
$
10,465 $
3,349
593
14,407 $
10,465 $
3,339
593
14,397 $
12,350
14,682
1,829
28,861
In May 2020, the Company issued $600.0 million in aggregate principal amount of senior subordinated unsecured convertible notes with a maturity
date of May 15, 2027. The 2027 Notes were issued to the public at par value and bear interest at the rate of 1.25% per annum. Interest is payable semi-
annually in cash in arrears on May 15 and November 15 of each year, beginning November 15, 2020. The 2027 Notes are convertible, at the option of the
holder into shares of the Company’s common stock. The initial conversion rate for the 2027 Notes is 7.2743 shares per $1,000 principal amount of the 2027
Notes, which represents a conversion price of approximately $137.47 per share, subject to adjustment under certain conditions. Following certain corporate
transactions, the Company will, in certain circumstances, increase the conversion rate for a holder that elects to convert its 2027 Notes in connection with
such corporate transactions by a number of additional shares of the Company’s common stock. A holder may convert fewer than all of such holder’s 2027
Notes so long as the amount of the 2027 Notes converted is an integral multiple of $1,000 principal amount. Net proceeds from the offering were
$585.8 million. In connection with the issuance of the 2027 Notes, the Company recorded a discount on the 2027 Notes of $13.5 million, which will be
accreted and recorded as additional interest expense over the life of the 2027 Notes.
The 2027 Notes are senior subordinated, unsecured obligations, and rank (i) subordinated in right of payment to the prior payment in full of all of the
Company’s existing and future senior debt, (ii) equal in right of payment with the Company’s existing and future senior subordinated debt, (iii) senior in right
of payment to the Company’s existing and future indebtedness that is expressly subordinated in right of payment to the notes, (vi) effectively subordinated to
the Company’s existing and future secured indebtedness, to the extent of the value of the collateral securing that indebtedness, and (v) structurally
subordinated to all existing and future indebtedness and other liabilities, including trade payables, and (to the extent the Company is not a holder thereof)
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
preferred equity, if any, of the Company’s subsidiaries. Upon the occurrence of a “fundamental change,” as defined in the indenture governing the 2027
Notes, the holders may require the Company to repurchase all or a portion of such holder’s 2027 Notes for cash at 100% of the principal amount of the 2027
Notes being purchased, plus any accrued and unpaid interest.
The offer and sale of the 2027 Notes and the shares of the Company’s common stock issuable upon conversion of the 2027 Notes have not been
registered under the Securities Act or any state securities laws and the 2027 Notes were offered only to qualified institutional buyers as defined in Rule 144A
under the Securities Act.
2024 Notes
In August 2017, the Company issued $495.0 million in aggregate principal amount of senior subordinated convertible notes with a maturity date of
August 1, 2024. The 2024 Notes were issued to the public at 98% of face value and bear interest at the rate of 0.599% per annum. Interest is payable semi-
annually in cash in arrears on February 1 and August 1 of each year, beginning February 1, 2018. The 2024 Notes are convertible, at the option of the holder
into shares of the Company’s common stock. The initial conversion rate for the 2024 Notes is 8.0212 shares per $1,000 principal amount of the 2024 Notes,
which represents a conversion price of approximately $124.67 per share, subject to adjustment under certain conditions. Following certain corporate
transactions, the Company will, in certain circumstances, increase the conversion rate for a holder that elects to convert its 2024 Notes in connection with
such corporate transactions by a number of additional shares of the Company’s common stock. A holder may convert fewer than all of such holder’s 2024
Notes so long as the amount of the 2024 Notes converted is an integral multiple of $1,000 principal amount. Net proceeds from the offering were $481.7
million. In connection with the issuance of the 2024 Notes, the Company recorded a discount on the 2024 Notes of $9.9 million, which will be accreted and
recorded as additional interest expense over the life of the 2024 Notes.
The 2024 Notes are senior subordinated, unsecured obligations, and rank (i) subordinated in right of payment to the prior payment in full of any of
the Company’s existing and future senior debt, (ii) equal in right of payment to any of the Company’s existing and future senior subordinated debt, (iii) senior
in right of payment to any of the Company’s existing and future indebtedness that is expressly subordinated in right of payment to the 2024 Notes, and (iv)
effectively subordinated to any of the Company’s existing and future secured indebtedness, to the extent of the value of the collateral securing that
indebtedness and structurally subordinated to all existing and future indebtedness and other liabilities, including trade payables, and (to the extent the
Company is not a holder thereof) preferred equity, if any, of the Company’s subsidiaries. Upon the occurrence of a “fundamental change,” as defined in the
indenture governing the 2024 Notes, the holders may require the Company to repurchase all or a portion of such holder’s 2024 Notes for cash at 100% of
the principal amount of the 2024 Notes being purchased, plus any accrued and unpaid interest.
See Note 16 to these Consolidated Financial Statements for further discussion of the effect of conversion of the Company's convertible debt on
earnings (loss) per common share.
Revolving Credit Facility
In October 2018, the Company entered into an unsecured revolving credit facility of up to $200.0 million, which includes a letter of credit subfacility
and a swingline loan subfacility. The credit facility is intended to finance ongoing working capital needs and for other general corporate purposes. In May
2021, the Company entered into an amendment agreement in respect of the credit facility, extending the maturity date from October 19, 2021 to May 28,
2024, among other changes. The amended credit facility contains financial covenants including a maximum leverage ratio and a minimum interest coverage
ratio. As of December 31, 2022, there were no amounts outstanding under the credit facility and the Company and certain of its subsidiaries that serve as
guarantors were in compliance with all covenants.
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(11) ACCUMULATED OTHER COMPREHENSIVE INCOME (LOSS)
The following table summarizes changes in the accumulated balances for each component of AOCI, including current period other comprehensive
income (loss) and reclassifications out of AOCI, for the periods presented.
AOCI balance at December 31, 2019
Other comprehensive income (loss) before
reclassifications
Less: gain (loss) reclassified from AOCI
Tax effect
Net current period other comprehensive income (loss)
AOCI balance at December 31, 2020
Other comprehensive income (loss) before
reclassifications
Less: gain (loss) reclassified from AOCI
Tax effect
Net current period other comprehensive income (loss)
AOCI balance at December 31, 2021
Other comprehensive income (loss) before
reclassifications
Less: gain (loss) reclassified from AOCI
Tax effect
Net current period other comprehensive income (loss)
AOCI balance at December 31, 2022
Unrealized Gains
(Losses) on Cash
Flow Hedges
Unrealized Gains
(Losses) on
Available-for-Sale
Debt Securities
Other
Total
16,614 $
3,565 $
(15) $
20,164
(23,462)
13,180
—
(36,642)
(20,028) $
34,379
(1,454)
—
35,833
15,805 $
29,045
36,624
—
(7,579)
8,226 $
976
552
(100)
324
3,889 $
(6,858)
—
1,596
(5,262)
(1,373) $
(13,967)
—
3,247
(10,720)
(12,093) $
15
—
—
15
— $
—
—
—
—
— $
—
—
—
—
— $
(22,471)
13,732
(100)
(36,303)
(16,139)
27,521
(1,454)
1,596
30,571
14,432
15,078
36,624
3,247
(18,299)
(3,867)
$
$
$
$
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
(12) REVENUE, CREDIT CONCENTRATIONS AND GEOGRAPHIC INFORMATION
The following table presents Total Revenues and disaggregates Net Product Revenues by product.
Net product revenues by product:
VIMIZIM
NAGLAZYME
PALYNZIQ
KUVAN
VOXZOGO
BRINEURA
FIRDAPSE
Total net product revenues marketed by the Company
ALDURAZYME net product revenues marketed by Sanofi
Total net product revenues
Royalty and other revenues
Total revenues
Years Ended December 31,
2021
2020
2022
$
$
663,739 $
443,794
255,032
227,577
169,128
154,333
—
1,913,603
128,422
2,042,025
54,014
2,096,039 $
623,145 $
380,449
237,474
285,776
5,855
128,034
—
1,660,733
122,765
1,783,498
62,777
1,846,275 $
544,257
391,298
170,983
457,736
—
110,192
1,288
1,675,754
130,107
1,805,861
54,594
1,860,455
The Company considers there to be revenue concentration risks for regions where Net Product Revenues exceed 10% of consolidated Net Product
Revenues. The concentration of the Company’s Net Product Revenues within the regions below may have a material adverse effect on the Company’s
revenues and results of operations if sales in the respective regions experience difficulties. The table below disaggregates total Net Product Revenues by
geographic region, which is based on patient location for Company's commercial products sold directly by the Company, except for ALDURAZYME, which is
sold exclusively by Sanofi worldwide.
United States
Europe
Latin America
Rest of world
Total net product revenues marketed by the Company
ALDURAZYME net product revenues marketed by Sanofi
Total net product revenues
Years Ended December 31,
2021
2020
2022
$
$
684,284 $
650,952
266,801
311,566
1,913,603
128,422
2,042,025 $
657,700 $
558,952
191,151
252,930
1,660,733
122,765
1,783,498 $
756,863
498,725
205,862
214,304
1,675,754
130,107
1,805,861
The following table illustrates the percentage of the Company’s total Net Product Revenues attributed to the Company’s largest customers for the
periods presented.
Customer A
Customer B
Customer C
Total
2022
Years Ended December 31,
2021
2020
16 %
12 %
9 %
37 %
18 %
14 %
10 %
42 %
16 %
15 %
12 %
43 %
On a consolidated basis, two customers accounted for 22% and 15% of the Company’s December 31, 2022 accounts receivable balance,
respectively, compared to December 31, 2021 when two customers accounted for 28% and 16% of the
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NOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
accounts receivable balance, respectively. As of December 31, 2022 and 2021, the accounts receivable balance for Sanofi included $68.8 million and $67.9
million, respectively, of unbilled accounts receivable, which becomes payable to the Company when the product is sold through by Sanofi. The Company
does not require collateral from its customers, but does perform periodic credit evaluations of its customers’ financial condition and requires prepayments in
certain circumstances.
The Company's global revenue sources and its business operations were impacted by the COVID-19 pandemic during the year ended
December 31, 2022, 2021, and 2020, mostly in the form of demand interruptions such as missed patient infusions and delayed treatment starts for new
patients. While the extent and duration of such effects remain uncertain and difficult to predict, the Company does not expect significant impacts to its
operating results and financial condition as a result of the COVID-19 pandemic in future periods.
The Company is mindful that conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency
exchange rates, natural disasters, the continuing effects of the COVID-19 pandemic, and supply chain disruptions, could affect the Company’s ability to
achieve its goals. In addition, the Company sells its products in countries that face economic volatility and weakness. Although the Company has historically
collected receivables from customers in certain countries, sustained weakness or further deterioration of the local economies and currencies may cause
customers in those countries to delay payment or be unable to pay for the Company’s products. The Company believes that the allowances for doubtful
accounts related to these countries, if any, are adequate based on its analysis of the specific business circumstances and expectations of collection for each
of the underlying accounts in these countries. The Company will continue to monitor these conditions and will attempt to adjust its business processes, as
appropriate, to mitigate macroeconomic risks to its business.
Long-lived assets, which consist of net property, plant and equipment and ROU assets are summarized by geographic region in the following table.
Long-lived assets by geography:
United States
Ireland
Rest of world
Total long-lived assets
(13) EQUITY COMPENSATION PLANS AND STOCK-BASED COMPENSATION
Equity Compensation Plans
Shares Available Under Equity Compensation Plans
December 31,
2022
2021
$
$
786,509 $
309,180
18,633
1,114,322 $
763,847
304,748
13,284
1,081,879
As of December 31, 2022, an aggregate of approximately 41.5 million unissued shares was authorized for future issuance under the Company’s
stock plans, which primarily includes shares issuable under the 2017 Equity Incentive Plan (2017 EIP) and the ESPP. Under the 2017 EIP, shares issued
and outstanding under the Amended and Restated 2006 Share Incentive Plan (the 2006 Share Incentive Plan) and the 2017 Equity Incentive Plan that
expire or are forfeited generally become available for future issuance under the 2017 Equity Incentive Plan. No additional awards will be granted under the
2006 Share Incentive Plan; however, there are vested and unvested awards outstanding under the 2006 Share Incentive Plan. The Company’s stock-based
compensation plans are administered by the Company’s Board of Directors (the Board), or designated Committee thereof, which selects persons to receive
awards and determines the number of shares subject to each award and the terms, conditions, performance measures and other provisions of the awards.
See Note 1 to these Consolidated Financial Statements for discussion regarding the valuation of equity awards.
2017 Equity Incentive Plan
The 2017 EIP provides for awards of RSUs and stock options as well as other forms of equity compensation. RSUs granted to employees generally
vest annually over a straight-line four-year period after the grant date. RSU Awards with Performance-based Vesting Conditions (PRSUs) generally vest over
a three-year period on a cliff basis three years after the grant date. Stock option awards granted to employees generally vest over a four-year period on a cliff
basis 12 months after the grant date and then monthly thereafter. The contractual term of stock option awards is generally 10 years from the grant date. As
of
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
December 31, 2022, approximately 27.7 million shares were authorized and reserved for future issuance under the 2017 Equity Incentive Plan.
Employee Stock Purchase Plan
The ESPP was initially approved in June 2006, replacing the Company’s previous plan, and was most recently amended in June 2019. Under
BioMarin’s ESPP, employees meeting specific employment qualifications are eligible to participate and can purchase shares on established dates (each
purchase date) semi-annually through payroll deductions at the lower of 85% of the fair market value of the stock at the commencement of the offering
period or each purchase date of the offering period. Each offering period will span up to two years. The ESPP permits eligible employees to purchase
common stock through payroll deductions for up to 10% of qualified compensation, up to an annual limit of $25,000. The ESPP is intended to qualify as an
“employee stock purchase plan” under Section 423 of the Internal Revenue Code. During the year ended December 31, 2022, the Company issued
0.3 million shares under the ESPP. As of December 31, 2022, approximately 7.0 million shares were authorized and 2.8 million shares reserved for future
issuance under the ESPP.
Board of Director Grants
On the date of the Company’s annual meeting of stockholders for a given year, each re-elected Independent Director receives an RSU grant valued
at $400,000, with the number of RSUs to be granted calculated based on the thirty-day trailing average closing price of the Company’s common stock on the
Nasdaq Global Select Market. The annual RSU grant for a director who has served for less than a year is prorated to the nearest quarter of the calendar
year. The RSUs subject to the annual award vest in full on the one-year anniversary of the grant date, subject to each respective Director providing service
to the Company through such vesting date. Upon election or appointment, a new Independent Director will receive an RSU grant on the same terms as the
annual award, pro-rated for amount and vesting to the nearest quarter for the time such new Independent Director will serve prior to the Company’s next
annual meeting of stockholders.
Stock-based Compensation
Stock-based compensation expense included on the Company’s Consolidated Statements of Operations for all stock-based compensation
arrangements was as follows:
Cost of sales
Research and development
Selling, general and administrative
Total stock-based compensation expense
Years Ended December 31,
2021
2020
2022
$
$
17,709 $
61,702
116,897
196,308 $
22,357 $
67,196
107,710
197,263 $
26,246
61,942
101,523
189,711
Stock-based compensation of $21.3 million, $20.0 million and $20.1 million was capitalized into inventory for the years ended December 31, 2022,
2021 and 2020, respectively. Capitalized stock-based compensation is recognized in Cost of Sales when the related product is sold.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Restricted Stock Units
Restricted Stock Unit Awards with Service-Based Vesting Conditions
Below is a summary of activity related to RSUs with service-based vesting conditions under the Company's plan for the year ended December 31,
2022:
Non-vested units as of December 31, 2021
Granted
Vested
Forfeited
Non-vested units as of December 31, 2022
Weighted
Average
Grant Date
Fair Value
80.38
79.43
81.68
79.55
79.55
Shares
4,437,512 $
2,266,150 $
(1,609,186) $
(574,730) $
4,519,746 $
The weighted-average grant date fair value per share of RSUs granted during the years ended December 31, 2022, 2021 and 2020, was $79.43,
$78.46 and $77.13, respectively. The total intrinsic value of restricted stock that vested and released in the years ended December 31, 2022, 2021 and 2020,
was $130.1 million, $117.2 million and $109.9 million respectively.
As of December 31, 2022, total unrecognized compensation cost related to unvested RSUs with service-based vesting conditions of $251.2 million
was expected to be recognized over a weighted average period of 2.5 years.
Restricted Stock Unit Awards with Performance-based Vesting Conditions
Below is a summary of activity related to RSUs with vesting conditions based on performance targets under the Company's plan for the year ended
December 31, 2022:
Non-vested units as of December 31, 2021
Granted
Vested
Forfeited
Non-vested units as of December 31, 2022
Weighted
Average
Grant Date
Fair Value
78.78
78.27
82.60
65.09
78.75
Shares
437,049 $
147,840 $
(102,489) $
(34,738) $
447,662 $
The weighted-average grant date fair value of the PRSUs for the years ended December 31, 2022, 2021 and 2020, was $78.27, $78.09 and
$84.17, respectively.
Non-vested PRSUs included grants with vesting contingent upon the achievement of a three-year Non-GAAP income target, upon the achievement
of a three-year Core Operating margin target, vesting contingent upon achievement of a three-year strategic goal target and vesting contingent upon
achievement of certain regulatory milestones. The awarded PRSUs generally vest over a three-year service period on a cliff basis. The Company evaluated
the targets in the context of its current long-range financial plan, its product candidate development pipeline and planned regulatory activity and determined
that attainment of each grant target was probable for accounting purposes commencing in the quarter granted. The number of shares that may be earned
range between 50% and 200% of the base PRSUs.
As of December 31, 2022, total unrecognized compensation expense related to non-vested PRSUs of $12.8 million was expected to be recognized
over a weighted average period of 1.2 years.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Restricted Stock Unit Awards with Market-based Vesting Conditions
The Compensation Committee and Board may grant RSUs with market-based vesting conditions (base TSR-RSUs) to certain executives. These
base TSR-RSUs vest, if at all, in full following a three-year service period only if certain total shareholder return (TSR) results relative to the Nasdaq
Biotechnology Index comparative companies are achieved. The number of shares that may be earned range between zero percent and 200% of the base
TSR-RSUs with a ceiling achievement level of 100% of the base TSR-RSUs in the event the Company’s TSR is above the 50th percentile but negative on an
absolute basis.
Below is a summary of activity related to RSUs with market-based vesting conditions under the Company's plan for the year ended December 31,
2022:
Non-vested units as of December 31, 2021
Granted
Vested
Forfeited
Non-vested units as of December 31, 2022
Weighted
Average
Grant Date
Fair Value
123.73
124.67
143.92
120.72
119.61
Shares
350,860 $
147,770 $
(89,640) $
(12,870) $
396,120 $
The grant date fair values and assumptions used to determine the grant date fair value of TSR-RSUs granted during the periods presented were as
follows:
Grant date fair value
Expected volatility
Dividend yield
Expected term
Risk-free interest rate
2022
$124.67
24.5 – 157.6%
0.0%
2.8 years
2.0%
Years Ended December 31,
2021
117.52
24.7 – 161.7%
0.0%
2.8 years
0.3%
2020
$112.12 – $217.65
21.3 – 159.9%
0.0%
2.5 – 2.8 years
0.2 – 0.4%
As of December 31, 2022, total unrecognized compensation expense of $17.1 million related to base TSR-RSUs was expected to be recognized
over a weighted average period of 1.8 years.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Stock Options and Purchase Rights
Stock Options
The following table summarizes activity under the Company’s stock option plans for the year ended December 31, 2022. All stock option grants
presented in the table had exercise prices not less than the fair value of the underlying common stock on the grant date:
Options outstanding as of December 31, 2021
Granted
Exercised
Expired and forfeited
Options outstanding as of December 31, 2022
Options unvested as of December 31, 2021
Exercisable at December 31, 2022
Shares
6,449,692 $
695,180 $
(943,038) $
(258,299) $
5,943,535 $
1,255,818 $
4,687,717 $
78.79
78.67
55.80
79.20
82.41
78.64
83.42
4.9 $
8.6 $
3.9 $
132,395
31,309
101,085
Weighted
Average
Exercise
Price
Weighted
Average
Remaining
Years
Aggregate
Intrinsic
(1)
Value
$
80,857
(1)
The aggregate intrinsic value for outstanding options is calculated as the difference between the exercise price of the underlying awards and the
quoted price of the Company’s common stock on the Nasdaq Global Select Market as of the last trading day for the respective year. The aggregate
intrinsic value of options outstanding and exercisable includes options with an exercise price below $103.49, the closing price of the Company’s
common stock on the Nasdaq Global Select Market on December 30, 2022.
The weighted-average fair value per stock options granted in the years ended December 31, 2022, 2021 and 2020, were $32.45, $31.61 and
$27.47, respectively. The total intrinsic value of options exercised during the years ended December 31, 2022, 2021 and 2020, were $32.1 million,
$40.7 million and $71.9 million, respectively, determined as of the date of option exercise. Upon the exercise of the options, the Company issues new
common stock from its authorized shares.
The assumptions used to estimate the per share fair value of stock options granted during the periods presented were as follows:
Expected volatility
Dividend yield
Expected term
Risk-free interest rate
2022
38.1 – 40.5%
0.0%
4.7 – 6.1 years
2.1 – 4.2%
Years Ended December 31,
2021
39.4 – 41.6%
0.0%
4.7 – 6.0 years
0.7 – 1.3%
2020
36.5 – 42.2%
0.0%
4.6 – 5.9 years
0.3 – 1.7%
As of December 31, 2022, total unrecognized compensation cost related to unvested stock options of $31.5 million was expected to be recognized
over a weighted average period of 2.5 years. The net tax expense from stock options exercised during the year ended December 31, 2022 was $0.2 million.
117
BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
Table of Content
Stock Purchase Rights
The assumptions used to estimate the per share fair value of stock purchase rights granted under the ESPP were as follows:
Expected volatility
Dividend yield
Expected term
Risk-free interest rate
2022
28.6 – 69.2%
0.0%
0.5 – 2.0 years
0.04 – 4.75%
Years Ended December 31,
2021
23.7 – 69.2%
0.0%
0.5 – 2.0 years
0.04 – 2.4%
2020
30.6 – 69.2%
0.0%
0.5 – 2.0 years
0.1 – 2.8%
As of December 31, 2022, total unrecognized compensation cost related to unvested stock purchase rights under the ESPP of $14.0 million was
expected to be recognized over a weighted average period of 1.3 years.
(14) OTHER EMPLOYEE BENEFITS
401(k) Plan
The Company sponsors the BioMarin Retirement Savings Plan (the 401(k) Plan) for eligible U.S. employees. The Company pays the direct
expenses of the 401(k) Plan and matches 100% of each participating employee’s eligible contributions, up to a maximum of the lesser of 6% of the
employee’s annual compensation or the annual statutory contribution limit. The Company’s matching contribution vests immediately and was approximately
$30.8 million, $31.6 million and $26.4 million for the years ended December 31, 2022, 2021 and 2020, respectively.
Deferred Compensation Plan
The Company maintains the Nonqualified Deferred Compensation (NQDC) plan under which eligible directors and key employee may defer
compensation. The NQDC prohibits the diversification of deferrals of Company stock. Company stock issued and held by the NQDC is accounted for
similarly to treasury stock in that the fair value of the employer stock was determined on the grant date and the shares are issued into the NQDC when the
restricted stock vests. The corresponding deferred compensation obligation is classified as equity with no changes in the fair value of Company stock held in
the NQDC recognized in earnings. Other contributions held in the NQDC are classified as trading securities, recorded at fair value with the corresponding
deferred compensation obligation classified as a liability and subsequent changes in the fair value of these non-BioMarin investments are recognized in
earnings in the period they occur.
See Note 7 to these Consolidated Financial Statements for additional discussion on the fair value and presentation of the NQDC assets and
liabilities.
(15) INCOME TAXES
The Provision for (Benefit from) Income Taxes was based on Income (Loss) before Income Taxes as follows:
U.S. Source
Non-U.S. Source
Income (loss) before income taxes
2022
Years Ended December 31,
2021
2020
(1)
$
$
(299,403) $
448,979
149,576 $
(259,258) $
183,908
(75,350) $
(169,614)
120,617
(48,997)
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The U.S. and foreign components of the Provision for (Benefit from) Income Taxes were as follows:
Years Ended December 31,
2021
2022
2020
(1)
Provision for (benefit from) income taxes
Federal
State and local
Foreign
Provision for (benefit from) deferred income taxes:
Federal
State and local
Foreign
$
12,798 $
5,058
42,246
60,102
(79,270)
(5,143)
32,326
(52,087)
Provision for (benefit from) income taxes
$
8,015 $
(2,038) $
1,339
5,037
4,338
(29,895)
(1,230)
15,517
(15,608)
(11,270) $
(15,073)
998
1,042
(13,033)
(46,124)
(5,321)
(838,548)
(889,993)
(903,026)
(1)
Certain December 31, 2020 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
In the third quarter of 2020, the Company completed an intra-entity transfer of certain intellectual property rights from a wholly owned foreign
subsidiary (tax resident in the Bahamas) to its wholly owned Irish subsidiary. The rights were sold to the Company’s Irish subsidiary where its ex-U.S.
regional headquarters are located and has significant manufacturing and commercial operations, to better align ownership of intellectual property rights with
how the business operates. The intra-entity transfer did not result in a taxable gain in 2020 in any jurisdiction including the U.S. as the transaction was
disregarded for U.S. tax purposes. The Company filed an election to treat the Irish subsidiary as a disregarded entity for U.S. income tax purposes in 2011.
The transaction resulted in a step-up in the tax basis in the transferred intellectual property rights and the Company’s Irish subsidiary recognized a deferred
tax asset for the book and tax basis difference of the transferred intellectual property rights. As a result, the Company recognized a deferred tax asset of
$835.1 million and related tax benefit on its Consolidated Financial Statements based on the fair value of the transferred intellectual property rights. The fair
value of the transferred intellectual property rights was determined utilizing the income approach which relied on projections of product-specific revenues and
the inclusion or exclusion of a terminal value for each product.
The tax deductions related to the amortization of these transferred intellectual property rights will be recognized in the future and any amortization
not deducted for tax purposes will be carried forward indefinitely under Irish tax laws. The Company expects to be able to realize the deferred tax asset
resulting from this transaction and has not recorded a valuation allowance as of December 31, 2022 and 2021.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The following is a reconciliation of the statutory federal income tax benefit to the Company’s effective tax rate:
Federal statutory income tax rate
State and local taxes
Orphan Drug & General Business Credit
Stock compensation expense
Foreign Source Income Subject to US Tax
Foreign tax rate differential
Section 162(m) limitation
Tax Reserves
Intra-entity transfer of assets
CARES act carryback claim
Valuation allowance/deferred benefit
Other
(1) (2)
Effective income tax rate
2022
December 31,
2021
2020
(3)
$
$
31,412 $
(1,017)
(35,674)
6,433
(5,644)
(4,051)
6,577
18,043
(18,752)
—
7,851
2,837
8,015 $
(15,824) $
509
(29,363)
7,859
16,878
(16,971)
6,304
15,530
(3,920)
—
6,821
907
(11,270) $
(10,289)
(3,467)
(44,114)
(1,101)
6,266
(16,238)
9,571
2,166
(852,338)
(2,201)
6,876
1,843
(903,026)
(1)
(2)
(3)
For the year ended December 31, 2022, the foreign rate differential included foreign local tax expense which was at an effective rate lower than the
U.S. statutory rate and is offset by the PRV income taxed at a higher tax rate.
For the year ended December 31, 2021, the foreign rate differential included foreign local tax expense which was at an effective rate lower than the
U.S. statutory rate and includes the recognition of the valuation allowance against a portion of the deferred tax assets of the Company’s Dutch
subsidiary of $9.3 million.
Certain December 31, 2020 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
The significant components of the Company’s net deferred tax assets were as follows:
Net deferred tax assets:
(1)
Net operating loss carryforwards
Tax credit carryforwards
Accrued expenses, reserves, and prepaids
Intangible assets
Capitalized research and development expenses
Stock-based compensation
Lease liabilities
Inventory
Other
Valuation allowance
Total deferred tax assets
Joint venture basis difference
Acquired intangibles
ROU Assets
Property, plant and equipment
Total deferred tax liabilities
Net deferred tax assets
December 31,
2022
2021
$
20,657 $
555,319
88,697
836,402
103,212
49,472
5,757
22,726
5,596
(116,299)
1,571,539
(745)
(1,138)
(5,347)
(58,897)
(66,127)
1,505,412 $
$
25,936
564,109
72,759
875,311
—
50,910
7,422
25,169
1,942
(109,176)
1,514,382
(1,665)
(1,250)
(6,808)
(54,498)
(64,221)
1,450,161
(1)
Certain December 31, 2021 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The increase in net deferred tax assets is primarily related to capitalization of research and development expenses offset by a decrease in
intangible assets.
Valuation allowances are provided to reduce the amounts of the Company's deferred tax assets to an amount that is more likely than not to be
realized based on an assessment of positive and negative evidence, including estimates of future taxable income necessary to realize future deductible
amounts. At the end of each period, the Company will reassess the ability to realize its deferred tax benefits. If it is more likely than not that the Company
would not realize the deferred tax benefits, a valuation allowance may need to be established against all or a portion of the deferred tax assets, which will
result in a charge to tax expense.
In the fourth quarter of 2021, the Company renegotiated a license agreement that resulted in lower royalty projections for its Dutch subsidiary. The
revised royalty projections required establishment of a valuation allowance on net operating loss deferred tax assets that were no longer expected to be
realizable. The valuation allowance also increased in 2021 due to the Company’s expectation that state R&D credits will not be utilized.
As of December 31, 2022, the Company had the following net operating loss and tax credit carryforwards, which if not utilized, will expire as follows:
Type
Federal net operating loss carryforwards
Federal R&D and orphan drug credit carryforwards
State net operating loss carryforwards
Dutch net operating loss carryforwards
Amount
3,628
585,322
186,594
38,912
$
$
$
$
Year
2030-2033
2024-2042
2023-2042
Indefinite
Not included in the table above are $152.7 million of state research credit carryovers that will carry forward indefinitely.
The Company’s net operating losses and credits could be subject to annual limitations due to ownership change limitations provided by Internal
Revenue Code Section 382 and similar state provisions. An annual limitation could result in the expiration of net operating losses and tax credit carryforward
before utilization. There are limitations on the tax attributes of acquired entities however, the Company does not believe the limitations will have a material
impact on the utilization of the net operating losses or tax credits.
The financial statement recognition of the benefit for a tax position is dependent upon the benefit being more likely than not to be sustainable upon
audit by the applicable taxing authority. If this threshold is met, the tax benefit is then measured and recognized at the largest amount that is greater than
50% likely of being realized upon ultimate settlement.
A reconciliation of the beginning and ending amount of unrecognized tax benefits for the years ended December 31, 2022 and 2021, is as follows:
Balance at beginning of period
Additions based on tax positions related to the current year
(Deletions) Additions for tax positions of prior years
Lapse of statute of limitations
Balance at end of period
December 31,
2022
2021
$
$
205,095 $
26,762
1,017
(18)
232,856 $
182,564
23,499
(786)
(182)
205,095
Included in the balance of unrecognized tax benefits as of December 31, 2022 were potential benefits of $223.3 million that, if recognized, would
affect the effective tax rate. The Company’s policy for classifying interest and penalties associated with unrecognized income tax benefits is to include such
items in the income tax expense. The total amount of accrued interest and penalties was not significant as of December 31, 2022. The Company believes it
will not have any material decreases in its previously unrecognized tax benefits within the next twelve months.
The Company files income tax returns in the U.S., Ireland and various foreign jurisdictions. The U.S. and foreign jurisdictions have statute of
limitations ranging from three to five years. However, carryforward tax attributes that were generated in 2014 and earlier may still be adjusted upon
examination by tax authorities.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
U.S. income and foreign withholding taxes have not been recognized on the excess of the amount for financial reporting over the tax basis of
investments in foreign subsidiaries that are essentially permanent in duration. This excess totaled approximately $17.3 million as of December 31, 2022,
which will be indefinitely reinvested; deferred income taxes have not been provided on such foreign earnings.
(16) EARNINGS (LOSS) PER COMMON SHARE
Potentially issuable shares of common stock include shares issuable upon the exercise of outstanding employee stock option awards, common
stock issuable under the Company’s ESPP, unvested RSUs, the Company's common stock held by the NQDC and contingent issuances of common stock
related to the Company's convertible debt.
The following table sets forth the computation of basic and diluted earnings (loss) per common share (common shares in thousands):
Numerator:
Net income (loss), basic
Add: Interest expense, net of tax, on the Notes
Net income/(loss), diluted
Denominator:
Weighted-average common shares outstanding, basic
Effect of dilutive securities:
Issuances under equity incentive plans
Common stock issuable under the Notes
Weighted-average common shares outstanding, diluted
Earnings (loss) per common share, basic
Earnings (loss) per common share, diluted
Years Ended December 31,
2021
2020
(1)
2022
$
$
$
$
141,561 $
—
141,561 $
(64,080) $
—
(64,080) $
854,029
8,313
862,342
185,266
182,852
180,804
3,697
—
188,963
—
—
182,852
0.76 $
0.75 $
(0.35) $
(0.35) $
4,030
6,844
191,678
4.72
4.50
(1)
Certain December 31, 2020 amounts have been corrected for an immaterial error identified in the third quarter of 2022. See Note 1 to these
Consolidated Financial Statements for details.
In addition to the equity instruments included in the table above, the table below presents potential shares of common stock that were excluded
from the computation of basic and diluted earnings (loss) per common share as they were anti-dilutive (in thousands):
Issuances under equity incentive plans
Common stock issuable under the Notes
Total number of potentially issuable shares
See Note 10 to these Consolidated Financial Statements for information on the Notes.
Years Ended December 31,
2021
2020
2022
8,148
8,335
16,483
12,450
8,335
20,785
7,836
—
7,836
(17) LICENSE AND COLLABORATION AGREEMENTS
In October 2019, the Company entered into a worldwide, exclusive licensing agreement with a third party for tralesinidase alfa (formerly referred to
as BMN 250), an investigational enzyme replacement therapy to treat Sanfilippo Syndrome Type B. In consideration, the Company received an upfront
payment of $3.0 million, a minority 15% equity ownership interest in the licensee, and is entitled to receive royalties on net sales of tralesinidase alfa and
milestone payments if certain development, regulatory and
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
sales milestones are met by the licensee. Subsequently, the third party licensee raised additional funding and issued the Company incremental shares to
maintain its 15% minority interest.
The Company evaluated the design and purpose of the third-party licensee and determined that it is a variable interest entity (VIE), as the equity-at-
risk is insufficient to support the licensee’s operations. The Company has concluded that it is not the primary beneficiary of the VIE as the Company does not
have the power to direct the activities of the VIE that most significantly impact its performance. The Company is accounting for the minority equity investment
at cost, less impairment, if any, adjusted for observable price changes, as it does not exercise significant influence over the operations of the licensee. Other
than providing the licensee with specified transition services, the Company has no other involvement with the operations of the VIE as of December 31,
2022. As a result, the Company's loss exposure is limited to the value of the equity investment of $12.6 million which is included in Other Assets on the
Company’s Consolidated Balance Sheets as of December 31, 2022.
In July 2017, the Company executed a license agreement with Sarepta Therapeutics (Sarepta) that provides Sarepta with global exclusive rights to
the Company’s Duchenne muscular dystrophy (DMD) patent estate for EXONDYS 51 and all future exon-skipping products. Under the license agreement,
Sarepta pays the Company royalties and may pay the Company certain milestone payments for exons 51, 45, 53 and possibly other exon-skipping products.
In the fourth quarter of 2021, the Company and Sarepta amended the license agreement to, among other things, make the license co-exclusive at a future
date and reduce future royalty rates.
On October 1, 2015, the Company entered into an agreement with Ares Trading S.A. (Merck Serono) under which the Company acquired all global
rights to KUVAN and PALYNZIQ from Merck Serono, with the exception of KUVAN in Japan. Previously, the Company had exclusive rights to KUVAN in the
U.S. and Canada and PALYNZIQ in the U.S. and Japan. Pursuant to the amended and restated KUVAN Agreement, if future sales milestones were met, the
Company was obligated to pay Merck Serono up to a maximum of €60.0 million, all of which were met as of December 31, 2022, €15.0 million of which was
unpaid as of December 31, 2022. Pursuant to the Pegvaliase Agreement, the Company also paid Merck Serono €125.0 million in cash when the PALYNZIQ
development milestones were achieved.
In October 2012, the Company licensed to Catalyst Pharmaceutical Partners, Inc. (Catalyst) the North American rights to develop and market
FIRDAPSE, the Company's former commercial product for the treatment of Lambert-Eaton myasthenic syndrome. In exchange for the North American rights
to FIRDAPSE, commencing in the first quarter of 2019 the Company receives royalties of 7% to 10% on net product sales of FIRDAPSE in North America. In
January 2020, the Company completed the sale of worldwide rights to FIRDAPSE to a third party. The Company retained the rights to receive the royalties
from Catalyst. See Note 1 to these Consolidated Financial Statements for further information about the FIRDAPSE sale.
In September 2007, the Company licensed to Asubio Pharma Co., Ltd. (a subsidiary of Daiichi Sankyo) exclusive rights to data and intellectual
property contained in the KUVAN New Drug Application. The Company receives royalties on net sales of the product in Japan.
The Company is engaged in R&D collaborations with various other entities. These provide for sponsorship of R&D by the Company and may also
provide for exclusive royalty-bearing intellectual property licenses or rights of first negotiation regarding licenses to intellectual property development under
the collaborations. Typically, these agreements can be terminated for cause by either party upon written notice.
(18) COMMITMENTS AND CONTINGENCIES
Contingencies
From time to time the Company is involved in legal actions arising in the normal course of its business. The process of resolving matters through
litigation or other means is inherently uncertain and it is possible that an unfavorable resolution of these matters could adversely affect the Company, its
results of operations, financial condition or cash flows. The Company’s general practice is to expense legal fees as services are rendered in connection with
legal matters, and to accrue for liabilities when losses are probable and reasonably estimable based on existing information. The Company accrues for the
best estimate of a loss within a range; however, if no estimate in the range is better than any other, then the minimum amount in the range is accrued.
Liabilities are evaluated and refined each reporting period as additional information is known. Any receivables for insurance recoveries for these liability
claims are recorded as assets when it is probable that a recovery will be realized.
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BIOMARIN PHARMACEUTICAL INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS - (Continued)
(In thousands of U.S. Dollars, except per share amounts or as otherwise disclosed)
The Company is involved in various purported shareholder class action and derivative lawsuits filed against the Company and certain officers and
directors. For example, there are shareholder class actions alleging violations under Sections 10(b) and 20(a) of the Securities Exchange Act of 1934 as
amended (the Exchange Act) for making materially false or misleading statements regarding information for two of its clinical products. The estimated long-
term loss contingency recorded on the Company's Consolidated Balance Sheets was $13.0 million as of December 31, 2022. The same amount was
recorded for expected insurance recoveries. Legal proceedings may occur that may result in a change in the estimated loss accrued by the Company. While
it is not feasible to predict the outcome of such proceedings and exposures with certainty, management believes this should not have a material adverse
effect on the Company’s Consolidated Balance Sheets, Statement of Operations or Statement of Cash Flows.
Contingent Payments
As of December 31, 2022, the Company was subject to contingent payments, primarily comprised of development, regulatory and commercial
milestones. Those considered reasonably possible totaled $762.5 million, which included $381.5 million and $210.0 million for two early stage development
programs licensed from third parties.
Other Commitments
The Company uses experts and laboratories at universities and other institutions to perform certain R&D activities. These amounts are included as
R&D expense as services are provided. In the normal course of business, the Company enters into various firm purchase commitments primarily to procure
active pharmaceutical ingredients, certain inventory-related items and certain third-party R&D services, production services and facility construction services.
As of December 31, 2022, such commitments were estimated at approximately $225.5 million, of which $188.7 million is expected to be paid in 2023. The
Company has also licensed technology, for which it is required to pay royalties upon future sales, subject to certain annual minimums.
124
Exhibit 10.35
BIOMARIN PHARMACEUTICAL INC.
2017 EQUITY INCENTIVE PLAN
RESTRICTED STOCK UNIT AWARD AGREEMENT
BioMarin Pharmaceutical Inc. (the “Company”) pursuant to its 2017 Equity Incentive Plan, as it may be amended from time to time (the “Plan”)
hereby grants you a number of restricted stock units (“RSUs”) in the amount set forth below (the “Award”). The Award is subject to all of the terms and
conditions set forth in this Restricted Stock Unit Award Agreement, including the exhibits, appendices and addenda attached hereto (this “Agreement”) and
the Plan. Unless otherwise defined herein, the terms defined in the Plan shall have the same defined meanings in this Agreement.
I.
NOTICE OF AWARD OF RSUs
A.
Terms of the Award. You have been granted RSUs, each of which represents the right to receive one share of Common Stock of the
Company (a “Share” and collectively, the “Shares”), subject to the terms and conditions of the Plan and this Agreement, as follows:
Participant Name (“you”):
Grant Date:
Total Number of RSUs Granted:
The RSUs will be adjusted in the event if changes in capital structure and similar events, as provided in Section 9 of the Plan.
B.
Vesting Schedule. The RSUs will vest in full immediately prior to the first annual meeting of the Company’s stockholders following the
Grant Date, conditioned on your Continuous Service through such date.
C.
D.
Settlement. Subject to Section V, each RSU will be settled by delivery to you of one Share within thirty (30) days following vesting.
Termination of Continuous Service. All unvested RSUs will be forfeited upon your termination of Continuous Service.
II.
MISCELLANEOUS
A.
Stockholder Rights. You will not be deemed to be the holder of, or have any of the rights of a stockholder with respect to, the RSUs
(including, without limitation, any voting rights or any right to dividends paid with respect to the Shares underlying the RSUs) unless and until the RSUs vest
and the Company has issued and delivered Shares to you and your name has been entered as a stockholder into the books and records of the Company.
B.
Securities Law Compliance. In no event will the Company deliver Shares upon vesting and settlement of the RSUs unless the Shares
are then registered under the Securities Act, and applicable state or non-U.S. securities law or, if not registered, the Committee has determined that the
issuance of the Shares would be exempt from the registration requirements of the Securities Act and applicable state securities laws. The issuance of
Shares also must comply with all other applicable laws and regulations governing the RSUs, including the requirements of any stock exchange on which the
Shares may be listed, and you may not be issued Shares if the Committee determines that such issuance would not be in material compliance with such
laws, regulations and listing requirements.
C.
Transferability. Except as permitted in the Plan, the RSUs are not transferable except by will or by the laws of descent and distribution.
Without limiting the generality of the foregoing, the RSUs may not be sold, assigned, transferred or otherwise disposed of, or pledged or hypothecated in any
manner (whether by operation of law or otherwise), and shall not be subject to execution, attachment or other process. Any assignment, transfer, sale,
pledge, hypothecation or other disposition of the RSUs or any attempt to make any such levy of execution, attachment or other process will cause the RSUs
to terminate immediately.
D.
Notices. Notices hereunder shall be mailed or delivered to the Company at its principal place of business and shall be mailed or delivered
to you at the address on file with the Company or, in either case, at such other address as one party may subsequently furnish to the other party in writing.
E.
Data Privacy Notice and Consent. You hereby explicitly and unambiguously consent to the collection, use and transfer, in electronic or
other form, of your personal data as described in this Agreement by and among, as applicable, the Company and is Affiliates for the exclusive purpose of
implementing, administering and managing your participation in the Plan. You understand that the Company and its Affiliates may hold certain personal
information about you, including, but not limited to, your name, home address and telephone number, date of birth, social insurance number or other
identification number, salary, nationality, job title, any Common Stock or directorships held in the Company, details of all RSUs or any other entitlement to
shares of Common Stock
1
Exhibit 10.35
awarded, canceled, vested, unvested or outstanding in your favor, for the purpose of implementing, administering and managing the Plan (“Data”). You
understand that Data may be transferred to any third parties assisting in the implementation, administration and management of the Plan, that these
recipients may be located in your country, or elsewhere, and that the recipient’s country may have different data privacy laws and protections than your
country. You understand that you may request a list with the names and addresses of any potential recipients of the Data by contacting your local human
resources representative. You authorize the recipients to receive, possess, use, retain and transfer the Data, in electronic or other form, for the purposes of
implementing, administering and managing your participation in the Plan, including any requisite transfer of such Data as may be required to a broker,
escrow agent or other third party with whom the shares of Common Stock received upon vesting of the RSUs may be deposited. You understand that Data
will be held only as long as is necessary to implement, administer and manage your participation in the Plan. You understand that you may, at any time,
view Data, request additional information about the storage and processing of Data, require any necessary amendments to Data or refuse or withdraw the
consents herein, in any case without cost, by contacting in writing your local human resources representative. You understand, however, that refusal or
withdrawal of consent may affect your ability to participate in the Plan. For more information on the consequences of your refusal to consent or withdrawal
of consent, you understand that you may contact your local human resources representative.
F.
Governing Law. The interpretation, performance, and enforcement of this Agreement shall be governed by the internal laws of the State
of Delaware without regard to that state’s conflict-of-laws rules.
G.
Integration. This Agreement constitutes the entire agreement between the parties with respect to this Award and supersedes all prior
agreements and discussions between the parties concerning such subject matter.
III.
MODIFICATIONS
This Agreement may be modified or amended at any time in accordance with the Plan; provided that you must consent in writing to any modification that
adversely or materially affects your rights or obligations under this Agreement.
IV.
NO RIGHT TO CONTINUOUS SERVICE
Neither the Company nor any of its Affiliates is obligated by or as a result of the Plan or this Agreement to continue your service with the Company or any
Affiliate, and neither the Plan nor this Agreement shall interfere in any way with the right of the Company and its Affiliates to terminate your Continuous
Service at any time.
V.
ACKNOWLEDGMENTS
In acknowledging the Award, you agree that:
(i)
the Plan is established voluntarily by the Company, it is discretionary in nature and may be modified, amended, suspended or terminated
by the Company at any time, unless otherwise provided in the Plan and this Agreement;
(ii)
the grant of the Award is voluntary and occasional and does not create any contractual or other right to receive future awards, or benefits
in lieu of RSUs even if RSUs have been awarded repeatedly in the past;
(iii)
(iv)
all decisions with respect to future grants of Awards, if any, will be at the sole discretion of the Committee;
your participation in the Plan is voluntary;
(v)
the Award is not part of normal or expected compensation or salary for any purpose, including, but not limited to, calculation of any
overtime, severance, resignation, termination, redundancy, end of service payments, bonuses, long-service awards, pension or retirement benefits or similar
payments and in no event should be considered as compensation for, or relating in any way to, past services for the Company or its Affiliates;
(vi)
the grant of the Award will not be interpreted to form an employment contract or relationship with the Company or its Affiliates;
(vii)
the future value of the underlying Shares is unknown and cannot be predicted with certainty;
(viii)
if you receive the shares of Common Stock upon settlement of the RSUs, the value of such shares may increase or decrease in value;
(ix)
in consideration of the grant of the Award, no claim or entitlement to compensation or damages arises from termination of the Award or
diminution in value of the shares of Common Stock received upon vesting and settlement of the RSUs resulting from termination of your Continuous Service
(for any reason whatsoever and whether or not in breach of local labor laws) and you irrevocably release the Company and its Affiliates from any such claim
that may arise; if, notwithstanding the foregoing, any such claim is found by a court of competent jurisdiction to have arisen, then, by signing this Agreement,
you shall be deemed irrevocably to have waived your entitlement to pursue such claim.
2
Exhibit 10.35
By executing this Agreement, you agree to be bound by all of the provisions of the Plan applicable to the Award, the provisions of which are hereby made a
part of this Agreement and incorporated herein by reference, and all interpretations, amendments, rules and regulations, which may from time to time be
promulgated and adopted pursuant to the Plan. You hereby agree to accept as binding, conclusive and final all decisions or interpretations of the Committee
upon any questions relating to the Plan and this Agreement. In the event of any conflict between the provisions of this Agreement and those of the Plan, the
provisions of the Plan shall control.
VI.
TAX WITHHOLDING; TAX IMPLICATIONS
The Committee and the Company assume no responsibility for individual income taxes, penalties or interest related to grant, vesting or settlement of the
RSUs. Neither the Committee, the Company nor any Affiliate makes any representation or undertaking regarding the treatment of any tax withholding in
connection with the grant, vesting or settlement of the RSUs. You should consult with your personal tax advisor regarding the tax ramifications, if any,
which result from receipt of the RSUs, the subsequent issuance, if any, of Shares on vesting and settlement of the RSUs, and subsequent
disposition of any such Shares.
It is the Board’s, the Committee’s and the Company’s intent that the RSUs and this Agreement be exempt from Section 409A of the Code (“Section 409A”) to
the extent applicable, and that this Agreement be administered accordingly. Notwithstanding anything to the contrary, to the extent that any payment or
benefit under this Agreement is determined by the Committee to constitute “nonqualified deferred compensation” subject to Section 409A and is payable to
you by reason of termination of your Continuous Service, then (a) such payment or benefit shall be made or provided to you only upon a “separation from
service,” as defined for purposes of Section 409A under applicable regulations, from the Company and (b) if you are a “specified employee” (within the
meaning of Section 409A and as determined by the Committee), such payment or benefit shall not be made or provided to you until first day of the seventh
month following the date of your separation from service from the Company and its Affiliates (or, if earlier, on the date of your death). Each payment under
this Agreement shall be treated as a separate payment under Section 409A. You hereby agree that the Committee and the Company do not have a duty to
design or administer the Plan or its other compensation programs in a manner that minimizes your tax liabilities. You will not make any claim against the
Board, the Committee and the Company or any of its officers, directors, employees or Affiliates related to tax liabilities arising from the RSUs.
You may request a copy of the Plan by contacting our General Counsel at (415) 506-6307 or BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA
94949, Attention: General Counsel.
You should carefully review the Plan and this Agreement before acknowledging this Award.
[Remainder of the page intentionally left blank.]
3
Exhibit 10.35
By acknowledging this award of RSUs, you consent to receive such documents by electronic delivery and to participate in the Plan through an on-line or
electronic system established and maintained by the Committee or another third party designated by the Committee.
BioMarin Pharmaceutical Inc.
By: [NAME]
Title:
Participant:
[Signed Electronically]
[NAME]
Acknowledgment Date:
Exhibit 10.36
BIOMARIN PHARMACEUTICAL INC.
2017 EQUITY INCENTIVE PLAN
RESTRICTED STOCK UNIT AWARD AGREEMENT
BioMarin Pharmaceutical Inc. (the “Company”) pursuant to its 2017 Equity Incentive Plan, as it may be amended from time to time (the “Plan”)
hereby grants you a number of restricted stock units (“RSUs”) in the amount set forth below (the “Award”). The Award is subject to all of the terms and
conditions set forth in this Restricted Stock Unit Award Agreement, including the exhibits, appendices and addenda attached hereto (this “Agreement”) and
the Plan. Unless otherwise defined herein, the terms defined in the Plan shall have the same defined meanings in this Agreement.
I.
NOTICE OF AWARD OF RSUs
A.
Terms of the Award. You have been granted RSUs, each of which represents the right to receive one share of Common Stock of the
Company (a “Share” and collectively, the “Shares”), subject to the terms and conditions of the Plan and this Agreement, as follows:
Participant Name (“you”):
Grant Date:
Total Number of RSUs Granted:
The RSUs will be adjusted in the event if changes in capital structure and similar events, as provided in Section 9 of the Plan.
B.
its entirety.
Vesting Schedule. The RSUs will vest pursuant to the schedule set forth in Exhibit A, which is attached hereto and incorporated herein in
C.
Settlement. Subject to Section V, each RSU will be settled by delivery to you of one Share within thirty (30) days following vesting.
D.
Termination of Continuous Service. Unless otherwise provided in Exhibit A, all unvested RSUs will be forfeited upon your termination of
Continuous Service.
II.
MISCELLANEOUS
A.
Stockholder Rights. You will not be deemed to be the holder of, or have any of the rights of a stockholder with respect to, the RSUs
(including, without limitation, any voting rights or any right to dividends paid with respect to the Shares underlying the RSUs) unless and until the RSUs vest
and the Company has issued and delivered Shares to you and your name has been entered as a stockholder into the books and records of the Company.
B.
Securities Law Compliance. In no event will the Company deliver Shares upon vesting and settlement of the RSUs unless the Shares
are then registered under the Securities Act, and applicable state or non-U.S. securities law or, if not registered, the Committee has determined that the
issuance of the Shares would be exempt from the registration requirements of the Securities Act and applicable state securities laws. The issuance of
Shares also must comply with all other applicable laws and regulations governing the RSUs, including the requirements of any stock exchange on which the
Shares may be listed, and you may not be issued Shares if the Committee determines that such issuance would not be in material compliance with such
laws, regulations and listing requirements.
C.
Transferability. Except as permitted in the Plan, the RSUs are not transferable except by will or by the laws of descent and distribution.
Without limiting the generality of the foregoing, the RSUs may not be sold, assigned, transferred or otherwise disposed of, or pledged or hypothecated in any
manner (whether by operation of law or otherwise), and shall not be subject to execution, attachment or other process. Any assignment, transfer, sale,
pledge, hypothecation or other disposition of the RSUs or any attempt to make any such levy of execution, attachment or other process will cause the RSUs
to terminate immediately.
D.
Recovery of Compensation; Insider Trading Policy. Notwithstanding anything to the contrary in this Agreement, the Shares issued on
settlement of an RSU under this Agreement and all amounts that may be received by you in connection with any disposition of any such Shares shall be
subject to applicable recoupment, “clawback” and similar provisions under applicable law, as well as the Company’s clawback policy in accordance with
Section 8(l) of the Plan. In addition, you may not be able to sell the Shares issued on settlement due to the restrictions of the Company’s insider trading
policy.
1
Exhibit 10.36
E.
Notices. Notices hereunder shall be mailed or delivered to the Company at its principal place of business and shall be mailed or delivered
to you at the address on file with the Company or, in either case, at such other address as one party may subsequently furnish to the other party in writing.
F.
Data Privacy Notice and Consent. You hereby explicitly and unambiguously consent to the collection, use and transfer, in electronic or
other form, of your personal data as described in this Agreement by and among, as applicable, the Company and is Affiliates for the exclusive purpose of
implementing, administering and managing your participation in the Plan. You understand that the Company and its Affiliates may hold certain personal
information about you, including, but not limited to, your name, home address and telephone number, date of birth, social insurance number or other
identification number, salary, nationality, job title, any Common Stock or directorships held in the Company, details of all RSUs or any other entitlement to
shares of Common Stock awarded, canceled, vested, unvested or outstanding in your favor, for the purpose of implementing, administering and managing
the Plan (“Data”). You understand that Data may be transferred to any third parties assisting in the implementation, administration and management of the
Plan, that these recipients may be located in your country, or elsewhere, and that the recipient’s country may have different data privacy laws and
protections than your country. You understand that you may request a list with the names and addresses of any potential recipients of the Data by
contacting your local human resources representative. You authorize the recipients to receive, possess, use, retain and transfer the Data, in electronic or
other form, for the purposes of implementing, administering and managing your participation in the Plan, including any requisite transfer of such Data as
may be required to a broker, escrow agent or other third party with whom the shares of Common Stock received upon vesting of the RSUs may be
deposited. You understand that Data will be held only as long as is necessary to implement, administer and manage your participation in the Plan. You
understand that you may, at any time, view Data, request additional information about the storage and processing of Data, require any necessary
amendments to Data or refuse or withdraw the consents herein, in any case without cost, by contacting in writing your local human resources
representative. You understand, however, that refusal or withdrawal of consent may affect your ability to participate in the Plan. For more information on the
consequences of your refusal to consent or withdrawal of consent, you understand that you may contact your local human resources representative.
G.
Governing Law. The interpretation, performance, and enforcement of this Agreement shall be governed by the internal laws of the State
of Delaware without regard to that state’s conflict-of-laws rules.
H.
Integration. This Agreement constitutes the entire agreement between the parties with respect to this Award and supersedes all prior
agreements and discussions between the parties concerning such subject matter.
III.
MODIFICATIONS
This Agreement may be modified or amended at any time in accordance with the Plan; provided that you must consent in writing to any modification that
adversely or materially affects your rights or obligations under this Agreement.
IV.
NO RIGHT TO CONTINUOUS SERVICE
Neither the Company nor any of its Affiliates is obligated by or as a result of the Plan or this Agreement to continue your employment or other service with
the Company or any Affiliate, and neither the Plan nor this Agreement shall interfere in any way with the right of the Company and its Affiliates to terminate
your Continuous Service at any time, subject to applicable law.
V.
ACKNOWLEDGMENTS
In acknowledging the Award, you agree that:
(i)
the Plan is established voluntarily by the Company, it is discretionary in nature and may be modified, amended, suspended or terminated
by the Company at any time, unless otherwise provided in the Plan and this Agreement;
(ii)
the grant of the Award is voluntary and occasional and does not create any contractual or other right to receive future awards, or benefits
in lieu of RSUs even if RSUs have been awarded repeatedly in the past;
(iii)
(iv)
(v)
all decisions with respect to future grants of Awards, if any, will be at the sole discretion of the Committee;
your participation in the Plan is voluntary;
the Award is outside the scope of your employment contract, if any;
(vi)
the Award is not part of normal or expected compensation or salary for any purpose, including, but not limited to, calculation of any
overtime, severance, resignation, termination, redundancy, end of service payments,
2
bonuses, long-service awards, pension or retirement benefits or similar payments and in no event should be considered as compensation for, or relating in
any way to, past services for the Company or its Affiliates;
Exhibit 10.36
(vii)
in the event that you are not an Employee, the grant of the Award will not be interpreted to form an employment contract or relationship
with the Company or its Affiliates;
(viii)
the future value of the underlying Shares is unknown and cannot be predicted with certainty;
(ix)
if you receive the shares of Common Stock upon settlement of the RSUs, the value of such shares may increase or decrease in value;
(x)
in consideration of the grant of the Award, no claim or entitlement to compensation or damages arises from termination of the Award or
diminution in value of the shares of Common Stock received upon vesting and settlement of the RSUs resulting from termination of your Continuous Service
(for any reason whatsoever and whether or not in breach of local labor laws) and you irrevocably release the Company and its Affiliates from any such claim
that may arise; if, notwithstanding the foregoing, any such claim is found by a court of competent jurisdiction to have arisen, then, by signing this Agreement,
you shall be deemed irrevocably to have waived your entitlement to pursue such claim.
By executing this Agreement, you agree to be bound by all of the provisions of the Plan applicable to the Award, the provisions of which are hereby made a
part of this Agreement and incorporated herein by reference, and all interpretations, amendments, rules and regulations, which may from time to time be
promulgated and adopted pursuant to the Plan. You hereby agree to accept as binding, conclusive and final all decisions or interpretations of the Committee
upon any questions relating to the Plan and this Agreement. In the event of any conflict between the provisions of this Agreement and those of the Plan, the
provisions of the Plan shall control.
VI.
NON-U.S. APPENDIX
Notwithstanding any provisions in this Agreement, the grant of RSUs may be subject to the special terms and conditions set forth in Appendix A to this
Agreement (including all addenda) for your country. Appendix A, including its addenda, constitute part of this Agreement.
VII.
TAX WITHHOLDING; TAX IMPLICATIONS
Regardless of any action the Company or your employer (the “Employer”) takes with respect to any or all income tax, social insurance, payroll tax, or other
tax-related items related to your participation in the Plan and legally applicable to you (“Tax-Related Items”), you acknowledge that the ultimate liability for all
Tax-Related Items is and remains your responsibility and may exceed the amount actually withheld by the Company or the Employer. You further
acknowledge that the Company and/or the Employer (i) make no representations or undertakings regarding the treatment of any Tax-Related Items in
connection with any aspect of the Award, including, but not limited to, the grant, vesting, and settlement of the Award, the issuance of shares of Common
Stock upon settlement of the Award, the subsequent sale of Common Stock acquired pursuant to such issuance and the receipt of any dividends and/or any
dividend equivalents; and (ii) do not commit to and are under no obligation to structure the terms of the grant or any aspect of the Award to reduce or
eliminate your liability for Tax-Related Items or achieve any particular tax result.
Prior to any relevant taxable or tax withholding event, you will pay or make adequate arrangements satisfactory to the Committee (in the Committee’s sole
discretion) to satisfy all withholding obligations. Unless the Committee expressly authorizes otherwise, you shall satisfy all tax withholding obligations arising
in connection with the vesting of RSUs by automatically having withheld, effective as of each Vesting Date (as defined on Exhibit A), such number of shares
of Common Stock underlying the RSUs that vest on such Vesting Date as have a Fair Market Value (calculated in accordance with the Plan) equal to the
amount of the applicable tax withholding obligations in connection with the vesting and settlement of such RSUs. The Company will withhold only the number
of shares required to satisfy your obligations for Tax-Related Items at the statutory minimum (or such higher amount as is acceptable without adverse
accounting consequences). You are deemed to have been issued the full number of shares of Common Stock at vesting, notwithstanding that a number of
the shares are held back solely for the purpose of paying the Tax-Related Items due as a result of any aspect of your participation in the Plan.
You shall pay to the Employer any amount of Tax-Related Items that the Employer may be required to withhold as a result of your participation in the Plan
that cannot be satisfied by the means previously described. The Company may refuse to issue or deliver the Shares, if you fail to comply with your
obligations in connection with the Tax-Related Items. Further, in consideration of the grant of the Award, no claim or entitlement to compensation or damages
arises if, in satisfying your (and/or the Employer’s) obligation for Tax-Related Items, the Company and/or the Employer withholds an amount in excess of the
amount legally required to be withheld, you irrevocably release the Company and the Employer from any such claim that may arise; if, notwithstanding the
foregoing, any such claim is found by a court of competent jurisdiction to have arisen, then, by signing this Agreement, you shall be deemed irrevocably to
have waived your entitlement to pursue such claim or damages.
3
Exhibit 10.36
The Committee and the Company assume no responsibility for individual income taxes, penalties or interest related to grant, vesting or settlement of the
RSUs. Neither the Committee, the Company nor any Affiliate makes any representation or undertaking regarding the treatment of any tax withholding in
connection with the grant, vesting or settlement of the RSUs. You should consult with your personal tax advisor regarding the tax ramifications, if any,
which result from receipt of the RSUs, the subsequent issuance, if any, of Shares on vesting and settlement of the RSUs, and subsequent
disposition of any such Shares.
It is the Board’s, the Committee’s and the Company’s intent that the RSUs and this Agreement be exempt from Section 409A of the Code (“Section 409A”) to
the extent applicable, and that this Agreement be administered accordingly. Notwithstanding anything to the contrary, to the extent that any payment or
benefit under this Agreement is determined by the Committee to constitute “nonqualified deferred compensation” subject to Section 409A and is payable to
you by reason of termination of your Continuous Service, then (a) such payment or benefit shall be made or provided to you only upon a “separation from
service,” as defined for purposes of Section 409A under applicable regulations, from the Company and (b) if you are a “specified employee” (within the
meaning of Section 409A and as determined by the Committee), such payment or benefit shall not be made or provided to you until first day of the seventh
month following the date of your separation from service from the Company and its Affiliates (or, if earlier, on the date of your death). Each payment under
this Agreement shall be treated as a separate payment under Section 409A. You hereby agree that the Committee and the Company do not have a duty to
design or administer the Plan or its other compensation programs in a manner that minimizes your tax liabilities. You will not make any claim against the
Board, the Committee and the Company or any of its officers, directors, employees or Affiliates related to tax liabilities arising from the RSUs.
You may request a copy of the Plan by contacting our General Counsel at (415) 506-6307 or BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA
94949, Attention: General Counsel.
You should carefully review the Plan and this Agreement before acknowledging this Award.
[Remainder of the page intentionally left blank.]
4
Exhibit 10.36
By acknowledging this award of RSUs, you consent to receive such documents by electronic delivery and to participate in the Plan through an on-line or
electronic system established and maintained by the Committee or another third party designated by the Committee.
BioMarin Pharmaceutical Inc.
By: [NAME]
Title:
Participant:
[Signed Electronically]
[NAME]
Acknowledgment Date:
Exhibit 10.37
BIOMARIN PHARMACEUTICAL INC.
2017 EQUITY INCENTIVE PLAN
STOCK OPTION AWARD AGREEMENT
BioMarin Pharmaceutical Inc. (the “Company”) pursuant to its 2017 Equity Incentive Plan, as it may be amended from time to time (the “Plan”)
hereby grants you an option to purchase the number of shares of Common Stock in the amount set forth below (the “Option”). The Option is subject to all of
the terms and conditions set forth in this Stock Option Award Agreement, including the exhibits, appendices and addenda attached hereto (this “Agreement”)
and the Plan. Unless otherwise defined herein, the terms defined in the Plan shall have the same defined meanings in this Agreement.
I.
NOTICE OF STOCK OPTION GRANT
A.
Terms of the Option. You have been granted an Option to purchase shares of Common Stock of the Company (the “Option Shares”),
subject to the terms and conditions of the Plan and this Agreement, as follows:
Participant Name (“you”):
Grant Date:
Exercise Price per Share:
Total Number of Shares Granted:
Type of Option:
Term/Expiration Date:
Nonstatutory Stock Option
10 years after the Grant Date
The Options will be adjusted in the event if changes in capital structure and similar events, as provided in Section 9 of the Plan.
B.
its entirety.
Vesting Schedule. The Option will vest pursuant to the schedule set forth in Exhibit A, which is attached hereto and incorporated herein in
C.
Termination of Continuous Service. Unless otherwise provided in Exhibit A, all unvested Option Shares will be forfeited upon your
termination of Continuous Service. Unless otherwise provided in Exhibit A, any vested Option Shares may be exercisable following the termination of
Continuous Service until the earliest of the following:
(i)
(ii)
three months following the termination of your Continuous Service other than for Cause, due to your death or Disability or after
attaining Retirement Eligibility Status;
the Expiration Date set forth above following a termination of Continuous Service after attaining Retirement Eligibility Status.
“Retirement Eligibility Status” shall mean that you (a) have the Company title of Vice President or a title more senior than Vice
President; and (b) have a combined age and years of Continuous Service equal to or more than 65 years;
(iii)
12 months following a termination of Continuous Service as a result of your Disability;
(iv)
12 months following the date of your death;
(v)
immediately upon a termination of Continuous Service for Cause; or
(vi)
the Expiration Date set forth above.
If, after your termination of Continuous Service, you do not exercise the Option within the applicable time frame above, the Option will terminate.
D.
Exercise. You may exercise the vested portion of the Option prior to the Expiration Date by (i) delivering a notice of exercise (in a form
designated by the Committee) or completing such other documents and/or procedures designated by the Committee for exercise and (ii) paying the Exercise
Price and any applicable
1
Exhibit 10.37
withholding taxes to the Company, stock plan administrator, or such other person as the Committee may designate, together with such additional documents
as the Committee may then require. To the extent permitted by applicable law and as determined by the Committee in its sole discretion, as set forth in a
notice of exercise designated by the Committee, the Exercise Price may be paid (A) by cash, check, bank draft or money order payable to the Company; (B)
pursuant to a program developed under Regulation T as promulgated by the Federal Reserve Board that, prior to the issuance of the stock subject to the
Option, results in either the receipt of cash (or check) by the Company or the receipt of irrevocable instructions to pay the aggregate Exercise Price to the
Company from the sales proceeds; (C) by delivery to the Company (either by actual delivery or attestation) of shares of Common Stock; or (D) by a “net
exercise” arrangement pursuant to which the Company will reduce the number of shares of Common Stock issuable upon exercise by the largest whole
number of shares with a Fair Market Value that does not exceed the aggregate Exercise Price, provided that the Company will accept a cash or other
payment from you to the extent of any remaining balance of the aggregate Exercise Price not satisfied by such reduction in the number of whole shares to
be issued. You may exercise the Option only for whole shares of Common Stock.
II.
MISCELLANEOUS
A.
Stockholder Rights. You will not be deemed to be the holder of, or have any of the rights of a stockholder with respect to, the Option
(including, without limitation, any voting rights or any right to dividends paid with respect to the Option Shares) unless and until the Option vests and you
exercise the Option in accordance with this Agreement and the Company has issued and delivered Common Stock to you and your name has been entered
as a stockholder into the books and records of the Company.
B.
Securities Law Compliance. In no event may you exercise the Option unless the shares of Common Stock issuable upon exercise are
then registered under the Securities Act, and applicable state securities law or, if not registered, the Committee has determined that the exercise and the
issuance of the shares would be exempt from the registration requirements of the Securities Act and applicable state or non-U.S. securities laws. The
exercise of the Option also must comply with all other applicable laws and regulations governing the Option, including the requirements of any stock
exchange on which the Stock may be listed, and you may not exercise your option if the Committee determines that such exercise would not be in material
compliance with such laws, regulations and listing requirements.
C.
Transferability. Except as permitted in the Plan, the Option is not be transferable except by will or by the laws of descent and distribution,
and is exercisable during your life only by you. Without limiting the generality of the foregoing, the Option may not be sold, assigned, transferred or otherwise
disposed of, or pledged or hypothecated in any manner (whether by operation of law or otherwise), and shall not be subject to execution, attachment or other
process. Any assignment, transfer, sale, pledge, hypothecation or other disposition of the Option or any attempt to make any such levy of execution,
attachment or other process will cause the Option to terminate immediately.
D.
Recovery of Compensation; Insider Trading Policy. Notwithstanding anything to the contrary in this Agreement, the Common Stock
issued under this Agreement and all amounts that may be received by you in connection with any disposition of any such Common Stock shall be subject to
applicable recoupment, “clawback” and similar provisions under applicable law, as well as the Company’s clawback policy in accordance with Section 8(l) of
the Plan. In addition, you may not be able to sell the shares of Common Stock issued on exercise due to the restrictions of the Company’s insider trading
policy.
E.
Notices. Notices hereunder shall be mailed or delivered to the Company at its principal place of business and shall be mailed or delivered
to you at the address on file with the Company or, in either case, at such other address as one party may subsequently furnish to the other party in writing.
F.
Data Privacy Notice and Consent. You hereby explicitly and unambiguously consent to the collection, use and transfer, in electronic or
other form, of your personal data as described in this Agreement by and among, as applicable, the Company and is Affiliates for the exclusive purpose of
implementing, administering and managing your participation in the Plan. You understand that the Company and its Affiliates may hold certain personal
information about you, including, but not limited to, your name, home address and telephone number, date of birth, social insurance number or other
identification number, salary, nationality, job title, any Common Stock or directorships held in the Company, details of all Options or any other entitlement to
shares of Common Stock awarded, canceled, vested, unvested or outstanding in your favor, for the purpose of implementing, administering and managing
the Plan (“Data”). You understand that Data may be transferred to any third parties assisting in the implementation, administration and management of the
Plan, that these recipients may be located in your country, or elsewhere, and that the recipient’s country may have different data privacy laws and protections
than your country. You understand that you may request a list with the names and addresses of any potential recipients of the Data by contacting your local
human resources representative. You authorize the recipients to receive, possess, use, retain and transfer the Data, in electronic or other form, for the
purposes of implementing, administering and managing your participation in the Plan, including any requisite transfer of such Data as may be required to a
broker, escrow agent or other third party with whom the shares of Common Stock received upon exercise of the Option may be deposited. You understand
that Data will be held only as long as is necessary to implement, administer and manage your participation in the Plan. You understand that you may, at any
time, view Data, request additional information about the storage and processing of Data, require any necessary amendments to Data or refuse or withdraw
the consents
2
herein, in any case without cost, by contacting in writing your local human resources representative. You understand, however, that refusal or withdrawal of
consent may affect your ability to participate in the Plan. For more information on the consequences of your refusal to consent or withdrawal of consent, you
understand that you may contact your local human resources representative.
Exhibit 10.37
of Delaware without regard to that state’s conflict-of-laws rules.
Governing Law. The interpretation, performance, and enforcement of this Agreement shall be governed by the internal laws of the State
agreements and discussions between the parties concerning such subject matter.
Integration. This Agreement constitutes the entire agreement between the parties with respect to this Option and supersedes all prior
G.
H.
III.
MODIFICATIONS
This Agreement may be modified or amended at any time in accordance with the Plan; provided that you must consent in writing to any modification that
adversely or materially affects your rights or obligations under this Agreement.
IV.
NO RIGHT TO CONTINUOUS SERVICE
Neither the Company nor any of its Affiliates is obligated by or as a result of the Plan or this Agreement to continue your employment or other service with
the Company or any Affiliate, and neither the Plan nor this Agreement shall interfere in any way with the right of the Company and its Affiliates to terminate
your Continuous Service at any time, subject to applicable law.
V.
ACKNOWLEDGMENTS
In acknowledging the Option, you agree that:
(i)
the Plan is established voluntarily by the Company, it is discretionary in nature and may be modified, amended, suspended or terminated
by the Company at any time, unless otherwise provided in the Plan and this Agreement;
(ii)
the grant of the Option is voluntary and occasional and does not create any contractual or other right to receive future awards, or benefits
in lieu of options even if options have been awarded repeatedly in the past;
(iii)
(iv)
(v)
all decisions with respect to future grants of Awards, if any, will be at the sole discretion of the Committee;
your participation in the Plan is voluntary;
the Option is outside the scope of your employment contract, if any;
(vi)
the Option is not part of normal or expected compensation or salary for any purpose, including, but not limited to, calculation of any
overtime, severance, resignation, termination, redundancy, end of service payments, bonuses, long-service awards, pension or retirement benefits or similar
payments and in no event should be considered as compensation for, or relating in any way to, past services for the Company or its Affiliates;
(vii)
in the event that you are not an Employee, the grant of the Option will not be interpreted to form an employment contract or relationship
with the Company or its Affiliates;
(viii)
the future value of the underlying Option Shares is unknown and cannot be predicted with certainty;
(ix)
if you receive the shares of Common Stock upon exercise of the Option, the value of such shares may increase or decrease in value;
(x)
in consideration of the grant of the Option, no claim or entitlement to compensation or damages arises from termination of the Option or
diminution in value of the Option shares of Common Stock received upon exercise of the Option resulting from termination of your Continuous Service (for
any reason whatsoever and whether or not in breach of local labor laws) and you irrevocably release the Company and its Affiliates from any such claim that
may arise; if, notwithstanding the foregoing, any such claim is found by a court of competent jurisdiction to have arisen, then, by signing this Agreement, you
shall be deemed irrevocably to have waived your entitlement to pursue such claim.
By executing this Agreement, you agree to be bound by all of the provisions of the Plan applicable to the Option, the provisions of which are hereby made a
part of this Agreement and incorporated herein by reference, and all interpretations, amendments, rules and regulations, which may from time to time be
promulgated and adopted pursuant to the Plan. You hereby agree to accept as binding, conclusive and final all decisions or interpretations of
3
Exhibit 10.37
the Committee upon any questions relating to the Plan and this Agreement. In the event of any conflict between the provisions of this Agreement and those
of the Plan, the provisions of the Plan shall control.
VI.
NON-U.S. APPENDIX
Notwithstanding any provisions in this Agreement, the grant of the Option may be subject to the special terms and conditions set forth in Appendix A to this
Agreement (including all addenda) for your country. Appendix A, including its addenda, constitute part of this Agreement.
VII.
TAX WITHHOLDING; TAX IMPLICATIONS
Regardless of any action the Company or your employer (the “Employer”) takes with respect to any or all income tax, social insurance, payroll tax, or other
tax-related items related to your participation in the Plan and legally applicable to you (“Tax-Related Items”), you acknowledge that the ultimate liability for all
Tax-Related Items is and remains your responsibility and may exceed the amount actually withheld by the Company or the Employer. You further
acknowledge that the Company and/or the Employer (i) make no representations or undertakings regarding the treatment of any Tax-Related Items in
connection with any aspect of the Option, including, but not limited to, the grant, vesting, and exercise of the Option, the issuance of shares of Common
Stock upon exercise of the Option, the subsequent sale of Common Stock acquired pursuant to such issuance and the receipt of any dividends and/or any
dividend equivalents; and (ii) do not commit to and are under no obligation to structure the terms of the grant or any aspect of the Option to reduce or
eliminate your liability for Tax-Related Items or achieve any particular tax result.
Prior to any relevant taxable or tax withholding event, you will pay or make adequate arrangements satisfactory to the Committee (in the Committee’s sole
discretion) to satisfy all withholding obligations. In this regard, in those cases where no such prior arrangement has been made (or where the amount of
money provided is insufficient to satisfy the applicable obligations) you authorize the Company and/or the Employer, in their discretion, to satisfy the
obligations with regard to all Tax-Related Items by one or a combination of the following: (i) withholding from your wages or other cash compensation paid to
you; (ii) withholding from proceeds of the sale of shares of Common Stock acquired upon exercise of the Option through a sale arranged by the Company
(on your behalf pursuant to this authorization); or (iii) withholding in shares of Common Stock to be issued upon exercise of the Option. If your obligation is
satisfied as described in (ii), the Company will endeavor to only sell only the number of shares required to satisfy your obligations for Tax-Related Items;
however, you agree that the Company may sell more shares than necessary to cover the Tax-Related Item, and that in such event, the Company will
reimburse you for the excess amount withheld, in cash and without interest. If your obligations are satisfied as described in (iii), the Company shall withhold
a number of shares otherwise deliverable at exercise having a Fair Market Value sufficient to satisfy the statutory minimum (or such higher amount as is
acceptable without adverse accounting consequences) of your estimated tax obligations. You are deemed to have been issued the full number of shares of
Common Stock subject to the exercise, notwithstanding that a number of the shares are held back solely for the purpose of paying the Tax-Related Items
due as a result of any aspect of your participation in the Plan.
You shall pay to the Employer any amount of Tax-Related Items that the Employer may be required to withhold as a result of your participation in the Plan
that cannot be satisfied by the means previously described. The Company may refuse to issue or deliver the shares or the proceeds of the sale of shares, if
you fail to comply with your obligations in connection with the Tax-Related Items. Further, in consideration of the grant of the Option, no claim or entitlement
to compensation or damages arises if, in satisfying your (and/or the Employer’s) obligation for Tax-Related Items, the Company and/or the Employer
withholds an amount in excess of the amount legally required to be withheld, you irrevocably release the Company and the Employer from any such claim
that may arise; if, notwithstanding the foregoing, any such claim is found by a court of competent jurisdiction to have arisen, then, by signing this Agreement,
you shall be deemed irrevocably to have waived your entitlement to pursue such claim or damages.
The Committee and the Company assume no responsibility for individual income taxes, penalties or interest related to grant or exercise of the Option.
Neither the Committee, the Company nor any Affiliate makes any representation or undertaking regarding the treatment of any tax withholding in connection
with the grant or exercise of the Option. You should consult with your personal tax advisor regarding the tax ramifications, if any, which result from
receipt of the Option, the subsequent issuance, if any, of Common Stock on exercise of the Option, and subsequent disposition of any such
Common Stock.
It is the Board’s, the Committee’s and the Company’s intent that the Option and this Agreement be exempt from Section 409A of the Code to the extent
applicable, and that this Agreement be administered accordingly. You hereby agree that the Committee and the Company do not have a duty to design or
administer the Plan or its other compensation programs in a manner that minimizes your tax liabilities. You will not make any claim against the Board, the
Committee and the Company or any of its officers, directors, employees or Affiliates related to tax liabilities arising from the Option.
You may request a copy of the Plan by contacting our General Counsel at (415) 506-6307 or BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA
94949, Attention: General Counsel.
4
Exhibit 10.37
You should carefully review the Plan and this Agreement before acknowledging this Option.
[Remainder of the page intentionally left blank.]
5
By acknowledging the Option, you consent to receive such documents by electronic delivery and to participate in the Plan through an on-line or electronic
system established and maintained by the Committee or another third party designated by the Committee.
Exhibit 10.37
BioMarin Pharmaceutical Inc.
By: [NAME]
Title:
Participant:
[Signed Electronically]
[NAME]
Acknowledgement Date:
Subsidiaries of BioMarin Pharmaceutical Inc. as of December 31, 2022
Exhibit 21.1
Name
BioMarin Commercial Ltd
BioMarin International Ltd
Direct Parent
BioMarin Pharmaceutical Inc.
BioMarin Commercial Ltd.
Ownership
100%
100%
Jurisdiction of Incorporation
Ireland
Ireland
Consent of Independent Registered Public Accounting Firm
Exhibit 23.1
We consent to the incorporation by reference in the registration statements (No. 333-136963, 333-168552, 333-181697, 333-188620, 333-197759, 333-
201504, 333-206094, 333-218695, 333-234231, 333-262824) on Form S-8 and in the registration statement (No. 333-212974) on Form S-3 of our reports
dated February 27, 2023, with respect to the consolidated financial statements of BioMarin Pharmaceutical Inc. and the effectiveness of internal control over
financial reporting.
/s/ KPMG LLP
San Francisco, California
February 27, 2023
I, Jean-Jacques Bienaimé, certify that:
1.
I have reviewed this Annual Report on Form 10-K of BioMarin Pharmaceutical Inc.;
CERTIFICATION
Exhibit 31.1
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make
the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by
this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the
financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4. The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-
15(f)) for the registrant and have:
a)
b)
c)
d)
designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by
others within those entities, particularly during the period in which this report is being prepared;
designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles;
evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most
recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely
to materially affect, the registrant’s internal control over financial reporting; and
5. The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to
the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a)
b)
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal
control over financial reporting.
Date: February 27, 2023
/S/ JEAN-JACQUES BIENAIMÉ
Jean-Jacques Bienaimé
Chief Executive Officer
I, Brian R. Mueller certify that:
1.
I have reviewed this Annual Report on Form 10-K of BioMarin Pharmaceutical Inc.;
CERTIFICATION
Exhibit 31.2
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make
the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by
this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the
financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4. The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-
15(f)) for the registrant and have:
a)
b)
c)
d)
designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by
others within those entities, particularly during the period in which this report is being prepared;
designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles;
evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most
recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely
to materially affect, the registrant’s internal control over financial reporting; and
5. The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to
the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a)
b)
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal
control over financial reporting.
Date: February 27, 2023
/S/ BRIAN R. MUELLER
Brian R. Mueller
Executive Vice President, Finance &
Chief Financial Officer
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
In connection with the Annual Report on Form 10-K of BioMarin Pharmaceutical Inc. (the Company) for the year ended December 31, 2022 as filed with the
Securities and Exchange Commission on the date hereof (the Report), we, Jean-Jacques Bienaimé, and Brian R. Mueller, hereby certify, pursuant to 18
U.S.C. §1350, as adopted pursuant to §906 of the Sarbanes-Oxley Act of 2002, that:
(1)
(2)
the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
/S/ JEAN-JACQUES BIENAIMÉ
Jean-Jacques Bienaimé
Chief Executive Officer
Date: February 27, 2023
/S/ BRIAN R. MUELLER
Brian R. Mueller
Executive Vice President, Finance &
Chief Financial Officer
Date: February 27, 2023
This certification accompanies the Form 10-K to which it relates, is not deemed filed with the Securities and Exchange Commission and is not to be
incorporated by reference into any filing of BioMarin Pharmaceutical Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of
1934, as amended (whether made before or after the date of the Form 10-K), irrespective of any general incorporation language contained in such filing.