th

7000000
– Herceptin:
 Launched 1998
 patent expiration 2014
 Controversy over price/efficacy
 Mylan & Biocon Biosimilars in India
6000000
5000000
4000000
3000000
2000000
1000000
– Kadcyla:
 Herceptin ADC
0
2006 2007 2008 2009 2010 2011 2012
 80% of US oncologists are prescribing only 9 months after FDA approval
 $100M in Q1 2014
 Peak sales estimate $2-5bn
2

– 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
3

– “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
4

Antibody-drug conjugate
Mylotarg (gemtuzumab ozogamicin)
Adcetris (brentuximab vedotin,
SGN-35) trastuzumab-DM1 inotuzumab ozogamicin lorvotuzumab mertansine
Sponsor company Cellular target Phase of development
Pfizer
Seattle
Genetics/Millennium
(Takeda)
Roche/Genentech/
Chugai
Pfizer
ImmunoGen
CD33
CD30
HER2
CD22
CD56 withdrawn from market
Approved
Approved phase III phase II glembatumumab vedotin Celldex Therapeutics GPNMB phase II
BT-062 Biotest + ImmunoGen CD138 phase I/II
SAR-3419
IMGN529
SGN-75
ASG-5ME
ASG-22ME
Sanofi + ImmunoGen
ImmunoGen
Seattle Genetics
Agensys (Astellas) +
Seattle Genetics
Agensys (Astellas) +
Seattle Genetics
CD19
CD37
CD70
SLC44A4
Nectin-4 phase I phase I phase I phase I phase I
5

– 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
6

Future location
…
7

Abbvie
(Antibody)
AMRI (Drug linker mfmg)
SAFC (Drug linker mfng)
Piramal healthcare
(Conjugation)
Pierre Fabre
(Fill/finish)
8

9

– 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)
10

April. 2014
Manufacturing of biologic device combination product.
270 jobs $100M
April. 2014
Global supply chain, quality fill finish & packaging.
250 jobs $100M
Aug. 2013
$300M investment in 400,000ft2 biotech drug substance facility
July. 2013
Establishing packaging, quality and supply chain function in Dublin
Feb. 2013
$44m investment in Biotech campus
Employs > 500
Employs > 100
Apr. 2012
$200m investment
Employs > 300
Apr. 2012
New Biotech facility in Cork
$420m/200 jobs
Apr. 2012 Jan. 2012
$500m investment in two strategic sites
$350m investment
Respiratory and sterile fill finish
Manufacturing & development
Employs > 700 200 new jobs
June. 2011
Manufacturing plant
$50m/100 jobs
11

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

Company Project Location Functions Second site
Athlone Jazz Nov 2012 Dublin Tech ops, SCM, QC, finance,
Legal, treasury
Regeneron June 2013 Dublin Regulatory affairs, SCM
Alexion
Endo
Sept 2013
50 +
250jobs
Dublin SCM, procurement
April 2014 Dublin SCM, Regulatory, quality, IP, commercial
Limerick
300 jobs
Athlone
70 jobs
Athlone
Biomarin May 2014
50 jobs
Dublin International Sales support,
SCM, procurement
Cork
100 jobs
13

– 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
– Government R&D support through IDA and SFI
– National Institute for Bioprocessing, Research and Training (NIBRT)
– Construction/engineering capacity and capability.
– Strategic sites.
– Cluster development

– 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
15

– 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
EPA
1%
(€800M in 2012)
IRCSET 3%
DJEI 3%
DAFM 4%
HRB
5%
Teagasc
7%
Others
6%
HEA
28%
IDA
Ireland
8%
SFI
20%
EI
14%
16

– 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
17

To learn more log on to idaireland.com
+353 1 6034285
Barry.heavey@ida.ie