Sol Pompe disease Argentina |

Genzyme developing a continuous integrated platform −Technical results are promising −But can we justify the platform from a business perspective? −And can we use economic modeling to guide development? Fully continuous biomanufacturing platform 2

High-productivity Smaller facilitiesMedia requirements Steady state Consistent operationSteady quality More automation Increased complexityLess labor Single-use tech Faster build timesReduced turnaroundClosed process Volume reduction Smaller facilitiesNo scale-up Step reduction Smaller facilitiesSimpler process Economic drivers for the continuous platform 3 CAPEXOPEXRisk Can we quantify these advantages and disadvantages? Universal platform Omni-product facilitiesCommon work forceFlexible infrastructure

Financial valuation methodology Outputs Cash Flow Projections Financial Indicators CVI, NPV, IRR, etc.Discount future costs Facility Estimates CAPEX/OPEX savings using the new platform Assessment Inputs Develop- ment Costs Launch Scenarios Estimate CAPEX/OPEX using BioSolve software Estimate platform dev costs and lay out a future product timeline Predict discounted cash flows for legacy & continuous platforms Calculate financial indicators (e.g., NPV) and make assessment

Use BioSolve software package −Define process (unit ops, scaling rules, assumptions) −Calibrate cost data (equipment, materials, labor, etc.) −Benchmark against previous internal and external projects −Biosolve capital estimates are acceptably accurate Facility estimates: CAPEX and OPEX 5 Facility Scale (Reactor # and Size) Facility CAPEX (Actual:Estimated) Facility A4X20,000L104% Facility B12X12,000L101% Facility C6X15,000L101% Facility D3X10,000L102% Facility E3X4,000L120%

Fed-batch 1X10,000L SS Batch 12 days 3000 Mcell·h/mL 3.5 g/L US DS Time IVCD Titer US DS Time VCD Titer Suspension perfusion 2X500L SU Continuous 60 days 100 Mcell/mL 1.4 g/L US DS Time VCD Titer Suspension perfusion 1X500L SU Continuous 60 days 100 Mcell/mL 0.5 g/L Facility estimates: Platform assumptions 6 mAb 500 kg/y Enzyme 20 kg/y Legacy PlatformContinuous Platform US DS Time VCD Titer Microcarrier perfusion 2X2,000L SS Batch 60 days 5 Mcell/mL 0.05 g/L

Facility estimates: Platform assumptions 7 mAb 500 kg/y Enzyme 20 kg/y CAPEX ($M)OPEX ($/g) 3X 1X 50X 8X 1.2X 1X 2X 1X Legacy Continuous

mAb CAPEX Cost impacts of the fully continuous platform 8 mAb OPEX Overall: –54% Overall: –20% % overall cost

Financial estimates can guide process development −(For example, CSPR and VCD targets) CAPEX/OPEX sensitivity analyses 9 Viable cell density Cell-Specific Perfusion Rate CAPEX Savings (Fed-Batch mAb – Continuous mAb) OPEX Savings (Fed-Batch mAb – Continuous mAb) Red = More Savings

Financial estimates can guide process development −(For example, CSPR and VCD targets) CAPEX/OPEX sensitivity analyses 10 Viable cell density Cell-Specific Perfusion Rate ΔNPV for a single facility (Fed-Batch mAb – Continuous mAb) Red = More Savings

Financial valuation methodology Outputs Cash Flow Projections Financial Indicators CVI, NPV, IRR, etc.Discount future costs Facility Estimates CAPEX/OPEX savings using the new platform Assessment Inputs Develop- ment Costs Launch Scenarios

Create a hypothetical product timeline with various mAb and enzyme product launches Calculate NPV for two scenarios −Legacy platforms (fed-batch and microcarrier perfusion) −Universal continuous platform Compare NPVs to estimate value of new platform Product launch scenario

Advanced Modeling – An Integrated Approach 13 Sales Profiles Development Profiles Stocking Strategy Portfolio NPV Dashboard Manufacturing Network Product Definition Product NPV In partnership with Biopharm Services Ltd.

Relative cash flow projections 14 Clear benefits to new platform (given the assumptions) Hundreds of millions of dollars in potential savings mAb OPEX Enzyme OPEX mAB CAPEX Enzyme CAPEX Development Cost discount rate = 7% ΔNPV for product portfolio

Relative cash flow projections 15 Different product launch scenarios can be investigated Continuous platform competes in a variety of scenarios Low demand Medium demand High demand ΔNPV for product portfolio

Infrastructure in place for economic modeling of future platforms Preliminary analysis shows strong, quantifiable business drivers for continuous platform −We will continue to revisit and improve assumptions −Additional sensitivity analyses −Expand comparisons to other platforms (e.g., disposable FB) Process development guidance −Cell density and CSPR are influential upstream parameters −Similar parameters will be found for downstream process Conclusions 16

Genzyme Late Stage Process Development Genzyme Capital Finance Genzyme Industrial Affairs Sanofi Biologics Research & Development Biopharm Services Acknowledgments 17