ADCs: the opportunity

ADCs: the opportunity

Barry Heavey, Head of Life SciencesIDA Ireland

June 20th, 2014

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ADC market opportunity

– Herceptin: Launched 1998 patent expiration 2014 Controversy over price/efficacy Mylan & Biocon Biosimilars in India

– Kadcyla: Herceptin ADC 80% of US oncologists are prescribing only 9 months after FDA

approval $100M in Q1 2014 Peak sales estimate $2-5bn

2006 2007 2008 2009 2010 2011 20120

1000000

2000000

3000000

4000000

5000000

6000000

7000000

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ADC market opportunity

– Brentuximab Millenium/Takeda pipeline antibody 2000-2010: Failed to show efficacy in clinical trials for Hodgkins

Lymphoma

– Brentuximab-vedotin (ADCetris) Partnership with Seattle Genetics to develop ADC version 34% complete remission, 40% partial remission Accelerated approval 2012 2015 sales target €420M

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ADC market opportunity

– “Biobetters” of existing Mabs: kadcyla

– “Reactivate” shelved Mabs: Adcetris

– Precedents for strong efficacy, fast track status

– Part of overall strong momentum in oncology €42Bn chemotherapy market growing through innovation

– Regulators/payors/clinicians getting familiar with ADC technology

– All major pharma companies now developing ADCs 2013: 100 ADCs in clinical trials

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Selected ADCs in clinical developmentAntibody-drug conjugate Sponsor company Cellular

target Phase of developmentMylotarg (gemtuzumab

ozogamicin) Pfizer CD33 withdrawn from market

Adcetris (brentuximab vedotin, SGN-35)

Seattle Genetics/Millenniu

m (Takeda)CD30 Approved

trastuzumab-DM1 Roche/Genentech/ Chugai HER2 Approved

inotuzumab ozogamicin Pfizer CD22 phase IIIlorvotuzumab mertansine ImmunoGen CD56 phase IIglembatumumab vedotin Celldex

Therapeutics GPNMB phase II

BT-062 Biotest + ImmunoGen CD138 phase I/II

SAR-3419 Sanofi + ImmunoGen CD19 phase I

IMGN529 ImmunoGen CD37 phase ISGN-75 Seattle Genetics CD70 phase I

ASG-5ME Agensys (Astellas) + Seattle Genetics SLC44A4 phase I

ASG-22ME Agensys (Astellas) + Seattle Genetics Nectin-4 phase I

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ADC market opportunity– Technology maturing

VC backing for novel technology• linker/conjugation chemistry/site-specific conjugation/payload

Investment in supporting services• Specialised CMOs – linkers, conjugation, high containment FF• Specialised CROs for QA/QC?

Investment by equipment/technology companies• Process engineering for conjugation• Improved containment tech• Improved analytics (process and product)• Single use ADC mfng systems

Specialised conferences, industry working groups etc etc

– Broad investment helps mitigate technology risk

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ADC Global Manufacturing Capabilities

…

Future location

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Case study: Adcetris supply chain

Abbvie (Antibody)

AMRI (Drug linker mfmg)

SAFC (Drug linker mfng)

Piramal healthcare

(Conjugation)

Pierre Fabre (Fill/finish)

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ADCs: B-2-B collaboration essential

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The opportunity for Ireland

– Ireland is winning high value manufacturing FDI Biotech DS/DP High potency API/formulation Single product sites transitioning to multiproduct sites Combination products: drug-device combos Global release testing Packaging Responsibility for management of complex supply chains

– VC funds being attracted to Ireland Can attract innovator companies

– Technology providers in Ireland Indigenous: PM, DPS, Prosys… MNC: GE, Waters, PPD, Millipore…

– Manufacturing a priority area for state investment (R&D grants)

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$2bn in Recent Investment Wins

April. 2014Global supply chain, quality fill finish & packaging.250 jobs $100M

Aug. 2013$300M investment in 400,000ft2 biotech drug substance facility

Feb. 2013 $44m investment in Biotech campus

Employs > 500

Apr. 2012New Biotech facility in Cork

$420m/200 jobs

June. 2011Manufacturing plant

$50m/100 jobs

Jan. 2012$350m investmentManufacturing & development200 new jobs

Apr. 2012$500m investment in two strategic sitesRespiratory and sterile fill finishEmploys > 700

April. 2014Manufacturing of biologic device combination product.270 jobs $100M

Apr. 2012$200m investment

Employs > 300

July. 2013 Establishing packaging, quality and supply chain function in Dublin

Employs > 100

Biopharma Cluster In Ireland

More than 5,000 people employed in Biotech development and manufacturing in 2014

7% employment growth per annum since 2009

NIBRT provided training in biopharma manufacturing to 2,000 people in 2013

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Recent supply chain management projects in pharmaCompany Project Locatio

nFunctions Second

siteJazz Nov 2012 Dublin Tech ops, SCM, QC, finance,

Legal, treasuryAthlone

Regeneron June 2013 Dublin Regulatory affairs, SCM Limerick300 jobs

Alexion Sept 201350 + 250jobs

Dublin SCM, procurement Athlone70 jobs

Endo April 2014 Dublin SCM, Regulatory, quality, IP, commercial

Athlone

Biomarin May 201450 jobs

Dublin International Sales support, SCM, procurement

Cork100 jobs

Why Ireland for biopharma FDI?– 9 of the world’s top 10 Pharmaceutical companies– 83 plants - 33 FDA approved.

– 17 Biopharmaceutical plants – Exports €55 billion in 2012.

– 24,500 people directly employed plus 24,500 indirect

– Strong regulatory track record – FDA/IMB

– National Institute for Bioprocessing, Research and Training (NIBRT)

– Construction/engineering capacity and capability.

– Strategic sites.– Cluster development

– Government R&D support through IDA and SFI

Developing an “ADC Cluster”

– IDA committed to supporting ADC investments through grant aid Biopharma companies: grants for in-house process R&D Supplier companies: grants for new product/service development

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Developing an “ADC Cluster”

– IDA committed to supporting ADC investments through grant aid Biopharma companies: grants for in-house process R&D Supplier companies: grants for new product/service development

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HEA28%

SFI20%EI

14%IDA Ire-

land8%

Teagasc7%

HRB5%

DAFM 4%DJEI 3%IRCSET 3%

EPA1%

Others6%

Government spend on

R&D (€800M in 2012)

Developing an “ADC Cluster”

– IDA committed to supporting ADC investments through grant aid Biopharma companies: grants for in-house process R&D Supplier companies: grants for new product/service development Indigenous companies – support from Enterprise Ireland Opportunities for B-2-B collaboration

– SFI/EI supports for industry academic collaborations/consortiums– NIBRT as a neutral venue/pilot scale test-bed/showcase facility

R&D programs = marketing collateral for FDI

– Networking/mobilising the sector Biopharma industry tech group Establish Subgroup on ADCs? Spot opportunities for B-2-B collaboration Develop proposals for publically funded research programs

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