BioMarin Pharmaceutical Annual Report 2008

FY2008 Annual Report · BioMarin Pharmaceutical

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Bi oMari n Phar maceutical In c.

200 8 Ann ual R epor t

THE SCIENCE OF SUCCESSBy leveraging expertise in
orphan drug development,
manufacturing and
commercialization,
Biomarin is providing
innovative treatment
options to patients with
rare diseases.

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 1

Messa ge fr oM the Ceo

Bu il ding a roBu st Pro duCt PiPeline

levera ging C oMPelling Biology

serving Patients arou nd the World

aC tively Purs uing advanCed treatMent oPtions

iMPr oving Patients’ liv es

fulfill ing unMet MediCal need s

2008 : YEAR IN REVIEW

BIoMARIN CeleBRATeD A NoTABly suCCessFul yeAR IN 2008, oNe ThAT MARkeD The CoMPANy’s

FIRsT Full yeAR oF PRoFITABIlITy, A veRy sIgNIFICANT MIlesToNe IN The oRgANIzATIoN’s 11-yeAR

hIsToRy. ReveNues INCReAseD 144 PeRCeNT As The Resul T oF sAles oF ThRee gRowINg CoMMeRCIAl

PRoDuCTs, NAglAzyMe ®, AlDuRAzyMe ® AND kuvAN®. The CoMPANy’s BusINess, ReseARCh AND

DeveloPMeNT eFFoRTs yIelDeD A RICh PRoDuCT PIPelINe AND The PRogRessIoN oF A PRoMIsINg

ColleCTIoN oF eARly-sTAge PRogRAMs Now uNDeR DeveloPMeNT .

Today, BioMarin is a fully integrated biophar-

maceutical company and one of the leading

pioneers in the highly complex industry of

orphan drug development. By leveraging a

secure financial foundation, growing revenues

and a uniquely refined methodology for the

development, manufacturing and commer-

cialization of therapies for rare diseases,

BioMarin is well positioned for continued

long-term growth.

We invite you to learn more about BioMarin’s

people, products and science in the pages

that follow.

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In a span of just
four years, BioMarin
revenue increased
nearly 16-fold. In
2008, the company
reported total revenue
of approximately
$300 million and
celebrated its first
profitable year.

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Pa g e 2 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

“in 2008, Biomarin achieved
important milestones that
will fuel future growth
opportunities in the orphan
disease industry.”

Jean-Jacques BienaiMé
Chief exeCutive OffiCer

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 3

A mEssAgE FROm THE CEO

a well known French poet once said, “l’homme est ainsi bâti: quand un sujet l’enflamme

l’impossibilité disparaît à son âme.” loosely translated, this means that for people who are inspired

with passion and determination, nothing is unattainable. For them, anything is possible. That is how

i would describe the people at BioMarin and the force that drives the company’s success.

There is a sense of exhilaration in our offices, hallways and laboratories that is fueled by a sense of

urgency to bring important drugs to market as quickly as possible. With collaboration, hard work and

determination, BioMarin’s team of physicians, researchers and business professionals is committed

to harnessing its expertise in biopharmaceutical science to improve the lives of people with rare

disease. Please join me in congratulating the entire team on the successes they achieved in 2008.

The year 2008 was a very important milestone in BioMarin’s history. We achieved our first profit-

able full year, with total revenues up 144 percent from 2007 to nearly $300 million, and increased

sales across all of our three products. We continue to build an exciting pipeline, with a clinical

portfolio featuring Peg-Pal for PKu and galns for MPs iV, and a preclinical lineup that provides

hope to many other patients with a variety of other rare diseases.

The year also brought with it the u.s. launch of Kuvan and we have been encouraged by the

progress made thus far in a market with unique complexities. We continue to look for new ways

to enhance our commercial efforts in this area and we remain very optimistic about the long-term

potential of the product.

other successes throughout the year included several regulatory achievements such as the approval

of naglazyme in Japan and south Korea, and the recent approval of Kuvan secured in the european

union by our partner Merck serono.

in 2008, BioMarin achieved important milestones that will fuel future growth opportunities in the

orphan drug industry. Today, as a fully integrated mid-cap biopharmaceutical company with three

products on the market, strong revenues and cash reserves of nearly $560 million, we are confi-

dent and well positioned for the long-term. in 2009, we will continue to advance our pipeline and

actively pursue valuable business development opportunities to bring increased value to patients,

shareholders and employees.

Thank you for your support.

sincerely,

Jean-Jacques Bienaimé

chief executive officer

Pa g e 4 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

“our product development
strategy focuses on leveraging
our expertise in treating patients
with rare genetic disorders and
carefully expanding our reach
into other areas of unmet
medical need.”

Dan oPPenheiMer, Ph.D.
viCe President,
POrtfOliO strategy

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 5

BUILDINg A ROBUsT PRODUCT P IP ELI NE

Meet BioMarin’s Morquio Core teaM:

aaron, Monica, Michael, celeste, Kris, Florence

each program illustrated on the bars below

candice, and cori (pictured on the left) are

represents the work of a collection of scientists,

members of one of BioMarin’s cross-functional

physicians, clinicians and other biopharmaceutical

core teams who work together to advance

professionals who mobilize their passion, urgency

individual product candidates from the research

and scientific expertise to bring important new

bench, into the clinic, and past the finish line on

therapies to patients with rare diseases.

to regulatory approval and commercialization.

PRECLINICAL TESTING

PHASE 1

PHASE 2

PHASE 3

BLA : NDA : MAA

COMMERCIAL

Naglazyme for MPS VI

Aldurazyme for MPS I

Kuvan for PKU

PEG-PAL for PKU

GALNS for MPS IVA

BMN-195 Utrophin upregulator for Duchenne Muscular Dystrophy

BMN-185 IgA Protease for IgA Nephropathy

Pictured on page 4 (left to right):
Aaron Olsen (Finance), Monica Miller (Program Management), Michael Vellard, Ph.D. (Research), Celeste Decker, M.D. (Medical/Clinical Affairs), Kris Antonsen, Ph.D. (Process Development),
Florence Lorget, Ph.D. (Pharm/Tox), Candice Henkel (Clinical Operations, Genetics) and Cori Leonard (Regulatory Affairs). Not pictured: Jill Jepson (Marketing). Background photo: Liam, Kuvan patient.

Pa g e 6 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

“as we advance our
research programs, it’s
inspiring to think that our
work has the potential to
help hundreds of patients
with rare diseases.”

Kieu ly
researCh assOCiate,
PrOCess develOPment

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 7

LEVERAgINg COmPELLINg BIOL OgY

FollowINg The suCCessFul DeveloPMeNT AND CoMMeRCIAlIzATIoN oF ThRee oRPhAN DRug

TheRAPIes Now PResCRIBeD To PATIeNTs ARouND The woRlD, BIoMARIN CoNTINues To ACTIvely

PuRsue The DeveloPMeNT oF ADDITIoNAl BIologICAl CoMPouNDs FoR A vARIeTy oF RARe DIseAses.

wITh The ADvANCeMeNT oF These ClINICAl AND PRe-ClINICAl ReseARCh PRogRAMs CoMes The

PossIBIlITy oF hoPe FoR huNDReDs MoRe PATIeNTs wITh DeBIlITATINg DIseAses lIke MoRquIo TyPe A

syNDRoMe (MPs IvA), DuCheNNe MusCulAR DysTRoPhy (DMD) AND IgA NePhRoPAThy, jusT To NAMe

A Few. As oF yeT, These PATIeNTs lACk ADequATe MeDICAl TReATMeNT oPTIoNs.

Peg-Pal for PKu

BioMarin expects to initiate a Phase 2 proof of

concept study for Peg-Pal in mid-2009. The trial

is designed to evaluate the safety and efficacy of

repeat injections in patients with PKu. if success-

ful, this new drug candidate will complement the

company’s existing drug, Kuvan, by treating an

additional population of PKu patients who do

not respond adequately to Kuvan.

galns for Morquio tyPe a syndroMe

galns (n-acetylgalactosamine-6-sulfate sulfatase)

recently entered the clinic and is designed to

address a population of underserved patients

who are very anxious to receive medical treat-

ment. By leveraging its expertise in the area of

enzyme replacement therapy, BioMarin is devel-

oping this product candidate with the hope that

it will prove safe and effective in the clinic and

advance quickly through the regulatory approval

process. This population of patients is estimated

to be roughly the same incidence rate as MPs i.

utroPhin uPregulator for
duChenne MusCular dystroPhy

an estimated one in 3,500 boys in the united

states and europe suffer from DMD, a chroni-

cally debilitating and ultimately fatal disease

that, as of yet, has no viable treatment options.

now in pre-clinical development, a small mol-

ecule inducer of the protein utrophin has dem-

onstrated a potential to help patients with DMD

by replacing a defective protein (dystrophin) in

their systems. inspired with the hope of success,

researchers, clinicians, patients and families

await further development of this much-needed

pre-clinical product candidate.

iga Protease for iga nePhroP athy

iga nephropathy is a chronic, often progres-

sive kidney disease that affects an estimated

one in 7,500 americans and commonly results

in end-stage renal failure. in vitro data has

demonstrated that iga protease may be effective

in the treatment of this disease and BioMarin

is currently evaluating the compound in vivo trials

with the hope of initiating an early develop-

ment plan in the future.

Page 8 | Biomarin pharmaceutical inc. | 2008 annual reportsE R VINg PATIENTs AROU ND T HE WORLD

every year, newly identified patients around the
world experience the benefits of naglazyme, the
only therapeutic treatment available for MPs Vi.
international demand for the drug is increasing
steadily in latin america, including Brazil, where the
drug recently received regulatory approval from
the national health surveillance agency. a growing
number of patients throughout eastern europe,
Western europe and the Middle east are also
receiving this much-needed therapy.

Biomarin pharmaceutical inc. | 2008 annual report | Page 9Pa g e 1 0 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

“we are constantly working
to enhance the clinical data
for all of our products. we
want to learn more aBout
the diseases we treat in
order to improve patient care,
compliance and maintenance
of long-term therapy.”

anDrea schaTz, r.n., B.s.n.
seniOr mediCal sCienCe liaisOn

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 1 1

ACTIVELY PURsUINg ADVANCED T REATmENT OPT IONs

BIoMARIN’s RIgoRous ReseARCh eFFoRTs Do NoT eND wITh The RegulAToRy APPRovAl AND CoMMeR-

CIAlIzATIoN oF ITs PRoDuCTs. IN oRDeR To CoNTINue BuIlDINg IMPoRTANT ClINICAl DATA, The CoMPANy

suPPoRTs A NuMBeR oF PosT-MARkeTINg TRIAls DesIgNeD To FuRTheR eNhANCe exIsTINg ReseARCh oN

loNg-TeRM PRoDuCT sAFeTy AND eFFICACy MeAsuRes.

For example, there are currently a number of

open and planned post-marketing studies for

Kuvan that will assess a range of measures,

including improvement in neurocognitive, social

and behavioral function, depression, anxiety,

short term memory, processing speed, execu-

tive function, and changes in bone density and

nutrition. These studies, along with an ongoing

PKu patient registry program will generate

additional data over time to support the use of

Kuvan. other similar programs for naglazyme

and aldurazyme are also in progress.

High Phe levels are toxic to the brain. Kuvan
is helping hundreds of patients better manage
their PKU by lowering Phe levels. In a Phase 3
placebo controlled trial, the drug was responsible
for a significant reduction in blood Phe levels
(p <0.001). The mean Phe level in the Kuvan
group was reduced by 29%, while the mean Phe
level in the placebo group increased by 3%. In
addition, the proportion of patients with Phe
levels <600 μmol/L was significantly higher in the
group treated with Kuvan (Levy HL, et al. Lancet.
2007;370: 504–510).

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Placebo group (n=47)
Sapropterin group (n=41)

Screening

–2

–1

Randomization time (weeks)

Pa g e 1 2 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

ImPROVINg PAT IENTs’ LIV Es

at just two-and-a-half years old, Jake quickly experienced
the benefits of Kuvan treatment for his PKu. While still
maintaining a Phe-restricted diet, Jake’s mother lisa
reports that his Phe levels have decreased considerably;
her fear and anxiety about her son’s serious disease have
also diminished.

Biomarin pharmaceutical inc. | 2008 annual report | Page 13Pa g e 1 4 | B i oMa r i n Ph a rMa c e uTi c a l i n c. | 2 0 0 8 an n u a l rePo r

“i am continuously
moved and inspired By
the strength, joy and
determination of these
extraordinary people
and their families.”

Dr. Paul harMaTz
CliniCal researCher,
Children’s hOsPital and
researCh Center Oakland

BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT | Pa g e 1 5

FULFILLINg UNmET mEDICAL NEEDs

PeDIATRIC gAsTRoeNTeRologIsT, DR. PAul hARMATz, oF ChIlDReN’s hosPITAl AND ReseARCh CeNTeR

oAklAND, Is oNe oF A gRouP oF PhysICIANs ARouND The CouNTRy PARTICIPATINg IN oNgoINg

ClINICAl TRIAls wITh PATIeNTs who ReCeIve NAglAzyMe TReATMeNT FoR MPs vI. he AND loNgTIMe

PATIeNT, IsABelle (pictured here), MeeT eveRy FRIDAy wITh oTheR loCAl PATIeNTs FoR weekly eNzyMe

RePlACeMeNT TheRAPy. They Also PlAyeD AN INsTRuMeNTAl Role IN The 2003-04 PhAse 3 ClINICAl

TRIAls FoR The DRug.

Today, four years after the commercialization

Patients with MPs i (muccopolysaccharidosis i),

of naglazyme, BioMarin clinicians and

are also receiving valuable therapy with a

physicians like Dr. harmatz continue to gather

similar enzyme replacement therapy, aldura-

important data that will enable further advance-

zyme, which was co-developed by BioMarin

ments in the treatment of patients with MPs Vi

and genzyme corp.

and other rare genetic diseases. currently, an

international group of physician investigators

is conducting a clinical surveillance program

to study the long-term safety and efficacy of

naglazyme therapy. This program will also

provide information about the natural history

of MPs Vi patients, both treated and untreated

with enzyme replacement therapy.

introduced in the united states in 2008, and

recently approved in the european union,

Kuvan for PKu (phenylketunuria) is enabling

patients to actively reduce the blood Phe

(phenylalanine) levels that, if elevated, are

toxic to the brain.

Pa g e 1 6 | BIoM A R I N PhA R M A Ce uT I C Al I N C . | 2 0 0 8 AN NuAl R ePoRT

C OR PORATE INFORmATION

BIoMARIN DeveloPs AND CoMMeRCIAlIzes INNovATIve BIoPhARMACeuTICAls FoR seRIous DIseAses AND MeDICAl

CoNDITIoNs. The CoMPANy’s PRoDuCT PoRTFolIo CoMPRIses ThRee APPRoveD PRoDuCTs AND MulTIPle ClINICAl

AND PReClINICAl DRug PRoDuCT CANDIDATes.

EXECUTIVES

Jean-Jacques Bienaimé
Chief Executive Officer

Jeffrey H. Cooper
Senior Vice President,
Chief Financial Officer

Henry J. Fuchs, M.D.
Senior Vice President,
Chief Medical Officer

Stephen Aselage
Senior Vice President,
Global Commercial Development

Robert A. Baffi, Ph.D.
Senior Vice President,
Technical Operations

G. Eric Davis
Vice President,
General Counsel & Secretary

Mark Wood
Vice President,
Human Resources

Jeff Ajer
Vice President,
Sales & Marketing Operations

Luisa Bigornia, Ph.D.
Vice President,
Intellectual Property

Lewis P. Chapman
Vice President,
Global Marketing

Steve Glass
Vice President,
General Manager, European Operations

Joshua A. Grass
Vice President,
Business & Corporate Development

Steven Jungles
Vice President,
Supply Chain

Daniel P. Maher
Vice President,
Product Development

Brian Mueller
Vice President,
Controller

Charles A. O’Neill, Ph.D.
Vice President,
Pharmacological Sciences

Dan Oppenheimer, Ph.D.
Vice President,
Portfolio Strategy

R. Andrew Ramelmeier, Ph.D.
Vice President,
Manufacturing and Process Development

Victoria Sluzky, Ph.D.
Vice President,
Quality and Analytical Chemistry

Gordon Vehar, Ph.D.
Vice President,
Research

Eduardo E. Von Pervieux
Vice President,
Information Technology, Chief Information Officer

Amy Waterhouse
Vice President,
Regulatory & Government Affairs

BOARD Of DIRECTORS

Jean-Jacques Bienaimé
Chief Executive Officer

Michael Grey
President & Chief Executive Officer,
Auspex Pharmaceuticals, Inc.

Elaine Heron
Chairman & Chief Executive Officer,
Amplyx Pharmaceuticals, Inc.

Joseph Klein, III
Managing Director,
Gauss Capital Advisors, LLC.

Pierre Lapalme
Former President & Chief Executive Officer,
North America Ethypharm, Inc.

V. Bryan Lawlis, Ph.D.
President & Chief Executive Officer,
Itero Biopharmaceuticals, Inc.

Alan Lewis, Ph.D.
President & Chief Executive Officer,
Juvenile Diabetes Research Foundation

Randy Meier
President & Chief Operating Officer
Advanced Medical Optics, Inc.

CORPORATE HEADqUARTERS

BioMarin Pharmaceutical Inc.
105 Digital Drive
Novato, CA 94949
Tel: 415.506.6700
Fax: 415.382.7889
Email: ir@bmrn.com
www.bmrn.com

BioMarin operates two subsidiary offices in
London, UK, and Sao Paulo, Brazil, with branch
offices in multiple countries around the world

STOCK LISTING

BioMarin Pharmaceutical is listed on the
NASDAQ Global Select Market under the
symbol BMRN (NASDAQ: BMRN).

INDEPENDENT ACCOUNTANTS

KPMG LLP
San Francisco, CA

TRANSfER AGENT

Bank of New York Mellon
480 Washington Boulevard
Jersey City, NJ 07310

US Tel. 800.522.6645
International Tel. 201.680.6578

FORWARD-LOOKING STATEMENT: This annual report contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without
limitation, statements about: the expectations of revenue and sales related to Naglazyme, Kuvan, and Aldurazyme; the financial performance of the BioMarin as a whole; PEG-PAL,
GALNS and other product candidates; the continued clinical development and commercialization of Aldurazyme, Naglazyme, Kuvan, and its product candidates; and actions by
regulatory authorities. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements.
These risks and uncertainties include, among others: our success in the continued commercialization of Naglazyme and Kuvan; Genzyme Corporation’s success in continuing the
commercialization of Aldurazyme; results and timing of current and planned preclinical studies and clinical trials; our ability to successfully manufacture our products and product
candidates; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning each of the de-
scribed products and product candidates; the market for each of these products and particularly Aldurazyme, Naglazyme and Kuvan; actual sales of Aldurazyme, Naglazyme and
Kuvan; Merck Serono’s activities related to Kuvan and factors detailed in BioMarin’s filings with the Securities and Exchange Commission, including, without limitation, the factors
contained under the caption “Risk Factors” in BioMarin’s 2008 Annual Report on Form 10-K, and the factors contained in BioMarin’s reports on Form 10-Q. Stockholders are urged
not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update
or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

Feature DVD Presentation: 2008 in Review

BioMarin invites you to view the enclosed DVD to learn more about the company’s milestone year

and become acquainted with some of the people behind the science who are responsible for the

company’s continued success. Please view the feature presentation and participate in an interactive

dialogue with company executives. To learn more about our patients, products and people, BioMarin
also welcomes you to visit us online at www.BMRN.com.

BioMarin Pharmaceutical Inc.
105 Digital Drive

Novato, CA 94949

Tel: 415.506.6700

Fax: 415.382.7889

Investor Relations: ir@bmrn.com