A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

A D V E R T I S E M E N T F E A T U R E

BioMarin Pharmaceutical Inc.www.biomarin.com

BioMarin—transformative medicines throughgenomic and development expertiseGlobal biotechnology company BioMarin focuses on developing and commercializing innovative therapiesthrough a range of modalities. The company’s diverse pipeline, spanning exploratory to marketed programs, reliesheavily on its genetic and genomic expertise, manufacturing capabilities, and long-term partnering models.

With a global footprint in over 75 countries, a port-folio of seven approved products, and an extensiveroster of clinical and preclinical product candidates,BioMarin has set an ambitious goal of becomingthe world leader in genetic medicines. For almost25 years, the mid-sized Bay Area biotech has beendeveloping and commercializing therapies for raregenetic diseases, harnessing multiple modalitiesto optimally treat each individual condition. Overthe years, BioMarin’s science and expertise haveyielded some of the most complex therapies in theworld to address rare genetic diseases. With thegoal of translating genetic discoveries into trans-formative medicines, the company leverages itsfoundation in genetics, genomics, and rare dis-eases to apply principles of drug development tolarger indications, sharpening its foci on genetic,metabolic, cardiac, neurological/neuromuscular,hematologic, and skeletal disorders across mul-tiple modalities, including gene, oligonucleotide,peptide, biologic, and small-molecule therapies.

More than two decades ago, BioMarin’s scien-tific foundation was built upon the research anddevelopment of enzyme-replacement therapiesfor five rare genetic conditions. The company’sapprovals yielded the first therapies for these seri-ous and life-threatening conditions. An increasedunderstanding of genetic diseases and how totreat them is described by BioMarin in terms offour core attributes: genetic, targeted, assessable,and transformational. In approaching its discov-ery and development through that lens, the com-pany (1) leverages genetic discoveries and toolsto ensure a clear understanding of the underly-ing disease mechanisms; (2) develops targetedtherapies that directly or proximally address thefundamental drivers of the diseases; (3) definesreadily assessable biomarkers or endpoints that

yield clear efficacy signals that reliably translateinto clinical benefit; and (4) ensures productshave a transformational impact on patients’lives by profoundly improving the way they feel,function, and survive (Fig. 1). “Rigorous adher-ence to these principles of drug developmenthas enabled success early in BioMarin’s devel-opment and will sustain us in the future,” saidHank Fuchs, President of Worldwide Researchand Development (WWRD) at BioMarin.

Today, BioMarin remains at the forefront of sci-entific discovery, following a modality-agnosticapproach to drug development. Combining thefour core attributes with recent advances ingenomic analysis and genetic understanding, thecompany has made it a strength to harness thera-peutic modalities—small molecules, biologics, orgene therapies—that provide optimal solutionsfor the conditions and biological mechanismsbeing targeted. The principal driver of this flexibil-ity has been fluency in genomic analysis, backedby a global network of expanding partnerships.Creative collaboration arrangements focusingon top science that best meets patients’ needshave resulted in a winning strategy for patients,the partners, and BioMarin.

“BioMarin’s scientists are driven to discoverand develop therapies to treat some of the mostcomplex diseases with unmet medical needs,”

said Fuchs. “We strive to explore avenues nottraditionally taken by drug developers. And ourexperience over the past almost 25 years hastaught us that this journey can be significantlyenhanced through collaboration with partnersthat are equally committed to fundamentallyimproving the lives of patients.”

With its core scientific capabilities and itsglobal footprint, BioMarin has put in place auniquely efficient and effective R&D organiza-tion, an innovative regulatory capability and theoperation and continuous expansion of its owncommercial manufacturing facilities (Fig. 2). Asa result, the majority of BioMarin’s therapeu-tic development programs have a shorter thanaverage timeline from investigational new drug(IND) filing to approval, and the company’s twocurrent good manufacturing practice (cGMP)biologics facilities and its award-winning genetherapy manufacturing facility are consideredbest in class globally.

Partnering on foundational researchFrom its inception, BioMarin has thrived bydeveloping therapies based on the most pre-cise science available on the root causes of adisease. Based on this approach, the companyhas amassed a robust pipeline of marketed prod-ucts, products in clinical trials, and exploratory

Leveraging genetic discoveries and tools, BioMarin has a clearunderstanding of the underlying disease mechanism

BioMarin can develop a targeted therapy that directly orproximally addresses the fundamental defect of the disease

Study designs use readily assessable biomarkers/endpointsthat yield clear efficacy signals and reliably translate intoclinical benefit

The medicine has a transformational impact on patients’ livesby profoundly improving the way they feel, function, andsurvive

Fig. 1 | BioMarin is committed to the translation of genetic discoveries into transformative medicines.The company does this by focusing on diseases with precisely understood mechanisms that are rootedin genetics, developing targeted therapeutic interventions that address the underlying cause of disease,utilizing readily assessable endpoints that are proximal to the disease pathway, and enablingtransformational changes to the way patients feel, function, and survive. This approach, which BioMarincalls its four core attributes, underlies the company’s scientific strategy, and allows BioMarin to approachtreatments for a range of diseases.

“BioMarin’s scientists aredriven to discover and

develop therapies to treatsome of the most complexdiseases with unmet medicalneeds

Hank Fuchs, President ofWorldwide Research and

Development, BioMarin

B20 | December 2021 | www.nature.com/biopharmdeal

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

A D V E R T I S E M E N T F E A T U R E

candidates developed in-house and as part ofexternal collaborations across genetic, metabolic,cardiac, neurological/neuromuscular, hemato-logic, and skeletal disorders.

BioMarin’s strategy is based on establishingcollaborations in foundational research to helpestablish the root causes of genetic diseasesand identify treatment targets to address them.Recently, for example, BioMarin initiated a col-laboration with the Seattle-based Allen Institutefor Brain Science to enable the creation of a newclass of gene therapies displaying a higher levelof precision to treat diseases of the central ner-vous system (CNS). While gene therapies are apromising approach to treat patients with suchconditions, a key hurdle for the development ofnovel techniques has been the need to targetspecific cells to improve safety and efficacy.

Together with researchers at the Allen Institute,BioMarin is developing modified adeno-asso-ciated viruses (AAVs) engineered to impactspecific classes of cells in the brain by means ofunique molecular enhancers that restrict viralgene expression to only those cell types relevantto a particular disease. The researchers at theAllen Institute originally developed the technol-ogy to study the behavior of individual brain celltypes by differentially labeling them and allowingtheir observation in vivo1,2.

“This collaborative effort to enhance the preci-sion of AAVs for therapeutic purposes exempli-fies BioMarin’s quest to bring novel therapies topatients with significant unmet medical needs,”said Brinda Balakrishnan, Group VP, Business andCorporate Development. “Combining our experi-ence in developing transformational therapies forrare genetic diseases with the Allen Institute’sintimate knowledge of the CNS lays the foun-dation for delivering multiple targeted investi-gational gene therapies to the clinic.” Anotherpotential outcome of the work, Balakrishnanadded, is that improved precision could reducethe development risk of gene-therapy candidates.The structure of the partnership includes exclu-sive licenses to BioMarin to each program forresearch, development, and commercialization.

Paving the path to the clinicBioMarin’s extensive experience and provenrecord in bringing therapies for rare genetic dis-eases from bench to bedside makes it the partnerof choice for researchers and companies look-ing to translate their early-stage discoveries intocandidates for clinical trials. By combining itsR&D, regulatory, manufacturing, and commercialcapabilities, BioMarin offers an incubator-likesetting for advancing a drug candidate through toan IND filing and beyond. Importantly, BioMarinhas demonstrated the experience and capabili-ties to conduct clinical trials almost anywhere inthe world, invaluable assets it has leveraged indeveloping targeting treatments for rare diseases.

A collaborative agreement between BioMarinand Toronto-based Deep Genomics to developoligonucleotide drug candidates in four indica-tions is a recent example of BioMarin’s partner-ships. Through this collaboration, BioMarin willadvance lead compounds identified and validatedusing Deep Genomics’ artificial intelligence (AI)drug-discovery platform into preclinical and

clinical development leveraging BioMarin’s expe-rience translating early therapeutic candidatesinto lead clinical compounds. The AI drug-dis-covery platform uses deep-learning techniquesto analyze massive amounts of in vitro and invivo data to identify targetable molecular mecha-nisms for oligonucleotide-based therapeutics.BioMarin has successfully applied such analyticapproaches to narrow down biological targets forpotential interventions for genetic short statureand skeletal dysplasia3.

“At BioMarin, we believe these translationalcollaborations will help unlock critical therapeuticpotential more effectively and efficiently,” notedBalakrishnan. “Using our experience and techni-cal capabilities to pave the path to the clinic forcompanies is a win–win scenario not only forour partners, but also our key stakeholders, andprimarily the patients in need of novel therapies.”As part of this collaboration, BioMarin receivesan exclusive option to each of the four diseaseprograms for development and commercializa-tion, while Deep Genomics receives paymentupfront and at defined development milestones.

Getting to the heart of translationAlso in 2020, BioMarin finalized a licensingagreement with Swiss gene-therapy companyDiNAQOR. The collaboration will focus on therapid advancement of DiNAQOR’s lead programin one of the most prevalent genetic heart dis-eases, hypertrophic cardiomyopathy (HCM),caused by mutations in myosin-binding proteinC3 (MYBPC3)—the gene that encodes cardiacmyosin-binding protein C (MyBP-C).

BioMarin is poised to bring its experience ingene therapy development to jointly advanceDiNAQOR’s lead HCM therapy through clinicaltrials. BioMarin’s manufacturing capabilitiesand global footprint will be invaluable factorsin maximizing the likelihood of success for thisnovel therapeutic approach.

“Our extensive experience with gene therapydevelopment was one of the principal triggersfor establishing this partnership with DiNAQORto develop new solutions for adults and childrenaffected by major genetic cardiomyopathies,”said Balakrishnan. “While we are initially focusingon MYBPC3 HCM, we entered this partnership

with a long-term commitment to provide theopportunity for tackling additional cardiomy-opathies in the future, leveraging DiNAQOR’sdeep expertise in genetic cardiomyopathies andrelevant model systems.”

In it for the long haulOne of BioMarin’s hallmarks is the company’slong-term commitment to patients and partnersalike. This is embodied in the company’s programto develop potentially the first gene therapy forhemophilia A. This genetic disease is caused bya missing or defective gene that codes for factorVIII, an essential blood-clotting protein. The pathto the clinic for BioMarin’s investigational fac-tor VIII gene therapy showcases the company’sphilosophy and enabling capabilities not only indrug development, but also in manufacturing.Licensed in 2013 from University College Londonand St. Jude Children’s Research Hospital, theearly-stage factor VIII gene therapy programfor hemophilia A was rapidly advanced throughcomprehensive preclinical research and the INDregulatory process to allow the first patients tobe treated in a phase 1/2 clinical trial at the endof 2015. BioMarin now has multiple clinical stud-ies underway for the treatment of hemophiliaA, including an ongoing phase 3 global study.According to Balakrishnan, “BioMarin enteredthis preclinical partnership with the goal ofadvancing the program all the way to regulatoryapproval and commercialization. This long-termvision helps us build trust and maximize thechances of success by navigating any challengesencountered along the way as a team with a com-mon goal. This ethos applies across the board toall our partnerships.”1. Graybuck, L. T. et al. Neuron 109, 1449–1464.e13 (2021).

2. Mich, J. K. et al. Cell Rep. 34, 108754 (2021).

3. Estrada, K. et al. Nat. Commun. 12, 2224 (2021).

Brinda Balakrishnan, Group VPCorporate and Business DevelopmentBioMarin Pharmaceutical Inc.San Rafael, CA, USATel: +1-415-506-6700Email: businessdevelopment@bmrn.com

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Fig. 2 | BioMarin—an end-to-end fully integrated biotechnology company. BioMarin seamlesslyintegrates (1) innovative drug discovery approaches based on the best available science, (2) a highlyefficient and effective R&D machine with strong regulatory capabilities, (3) best-in-class commercialmanufacturing capabilities, and (4) a global commercial infrastructure covering the range from patientidentification to sales in over 75 countries. cGMP, current good manufacturing practice; IND,investigational new drug; R&D, research and development.

www.nature.com/biopharmdeal | December 2021 | B21