ADCs: the opportunity

1. ADCs: the opportunity Barry Heavey, Head of Life Sciences IDA Ireland June 20th, 2014

2. ADC market opportunity • Herceptin: • Launched 1998 • patent expiration 2014 • Controversy over price/efficacy • Mylan& BioconBiosimilars 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

3. 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

4. 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

5. Selected ADCs in clinical development

6. 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 etcetc • Broad investment helps mitigate technology risk

7. ADC Global Manufacturing Capabilities Future location …

8. Case study: Adcetris supply chain

9. ADCs: B-2-B collaboration essential

10. 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)

11. $2bn in Recent Investment Wins July. 2013 Establishing packaging, quality and supply chain function in Dublin Employs > 100 Feb. 2013 $44m investment in Biotech campus Employs > 500 Aug. 2013 $300M investment in 400,000ft2 biotech drug substance facility April. 2014 Global supply chain, quality fill finish & packaging. 250 jobs $100M April. 2014 Manufacturing of biologic device combination product. 270 jobs $100M Apr. 2012 $500m investment in two strategic sites Respiratory and sterile fill finish Employs > 700 Jan. 2012 $350m investment Manufacturing & development 200 new jobs June. 2011 Manufacturing plant $50m/100 jobs Apr. 2012 $200m investment Employs > 300 Apr. 2012 New Biotech facility in Cork $420m/200 jobs

12. 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 biopharmamanufacturing to 2,000 people in 2013

13. Recent supply chain management projects in pharma

14. 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

15. 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

16. 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 Government spend on R&D (€800M in 2012)

17. 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

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