1. Medicines Patent Pool – Strictly Confidential, Not for Circulation Licensing Technology and Intellectual Property for the Development of Paediatric Formulations July 1, 2013 Sandeep Juneja Business Development Director Medicines Patent Pool

2. Medicines Patent Pool – Strictly Confidential, Not for Circulation Why Focus on Paediatrics General impression is that the paediatric market is small – It is: at 0.63Mn on treatment, <7% of all PLHIV treated – And fragmented: multiple regimens; standalone formulations Under new guidelines, all children 5y with CD4<500 – Increased treatment gap – Paediatric treatment options unfortunately remain complex – 9 possible regimens (6 triple FDCs) required in first-line if all recommendations are to be covered Of which only 1 triple FDC exists presently Treatments need to be adapted for children and RLS And IP issues need to be resolved All above throws up challenges unique to paediatrics Justifies special focus All above throws up challenges unique to paediatrics Justifies special focus

3. Medicines Patent Pool – Strictly Confidential, Not for Circulation When Considering Licences Questions to consider when seeking licences 1.Obvious, first question: extent of IP coverage in L&MICs 2.Possible formulations? FDCs possible? Dose of the FDC in different weight bands? 3.Is technology available for the FDC or can be made available? Source? 4.Would there be a viable generic market? How many generics can it sustain? 5.Would efficacy trials be required? If so, who will conduct them? Financing?

4. Medicines Patent Pool – Strictly Confidential, Not for Circulation Regimens Required per 2013 Guidelines 1 st line2 nd lineResistant patients Infants and children <3y ABC or AZT/3TC/LPV/r (P) ABC or AZT/3TC/NVP (A)  Infants and children <3y* No change or AZT or ABC or TDF/3TC/NVP or EFV AZT or ABC or TDF/3TC/LPV/r Regimens based on RAL and/or ETV and/or DRV/r Children >3y <10y ABC/3TC/EFV (P) ABC or TDF/3TC+NVP (A) TDF/3TC/EFV(A) AZT/3TC/NVP or +EFV (A)**  Children >3y <10y*** AZT/3TC/LPV/r ABC or TDF/3TC/LPV/r  Children >10y TDF/3TC/EFV (P) AZT/3TC/NVP or +EFV (A) TDF/3TC/NVP (A)  Children >10y AZT/3TC/LPV/r ABC or TDF/3TC/LPV/r AZT/3TC/LPV/r  “/” is used when FDC exist or is possible, “+” is used when FDC is difficult due to size or different dosages. * EFV can only be used in >3y. **Most children on treatment are currently receiving this regimen (300,000 ch) and d4T/3TC/NVP (150,000 ch). In both cases, they will require ABC/3TC/LPV/r after failure. *** ATV/r can be used alternatively in children>6y. (P)= preferred, (A)= alternative Patented in L&MICs Licensed to MPP

5. Medicines Patent Pool – Strictly Confidential, Not for Circulation Other future alternatives still in development First lineSecond line ABC/3TC/DTG ABC/3TC/ATV/r TAF/3TC/DTG Licensed to MPP Patented in L&MICs MPP in negotiations

6. Medicines Patent Pool – Strictly Confidential, Not for Circulation Treatment Options for Paediatrics Product Line of Treatme ntIP Technology RequirementDosingMarket size Clinical Trials for FDC AZT/3TC/NVPFL and SL ABC/3TC/NVPFL and SL ABC/3TC/EFVFL and SL TDF/3TC/EFVFL and SL AZT/3TC/LPV/rFL and SL ABC/3TC/LPV/rFL and SL ABC/3TC/DTGFL TAF/3TC/DTGFL ABC/3TC/ATV/rSL Majority of the formulations required have more than one challenge from licensing to filing

7. Medicines Patent Pool – Strictly Confidential, Not for Circulation Potential First Line and Second Line Options ProductIP Technology RequirementDosingMarket size Clinical Trials for FDC AZT/3TC/NVPNot requiredDeveloped60/30/50mgEstablishedDeveloped ABC/3TC/NVP Licence for ABC through MPPDistab required WHO recommendation 60/30/50mgAlternate FL; SL CT may not be required ABC/3TC/EFV Licence for ABC through MPPDistab required Possible strength 120/60/100 mg Potentially big; preferred option in 3y-10y CT may not be required TDF/3TC/EFV Licence for TDF through MPP Taste masking; distab required WHO recommendation 75/75/150mg Potentially big; preferred option in >10y CT may not be required AZT/3TC/LPV /rLPV/r patented Taste masking; heat stable. Gx developing WHO recommendation 30/15/40/10mg Potentially big; preferred FL option in children 3yDNDi? ABC/3TC/LPV /r Licence for ABC through MPP; LPV/r patented Taste masking; heat stable. Gx developing WHO recommendation 30/15/40/10mg Potentially big; preferred 1st line option in children <3yDNDi?

8. Medicines Patent Pool – Strictly Confidential, Not for Circulation Potential Future Options ProductIP Technology RequirementDosingMarket size Clinical Trials for FDC ABC/3TC/DTG VL for ABC through MPP; MPP in negotiations for DTG Not expected to be complex; ViiV-MPP MOU entails tech transfer Dosage ratio to be defined Potentially interesting Ongoing CT by ViiV TAF/3TC/DTG MPP is in negotiations for DTG as well as TAFUnknown Dosage ratio to be defined Potentially interestingRequired ABC/3TC/ATV /r RTV patented; MPP in negotiations for ATV Taste masking; melt extrusion Dosage ratio to be defined Potentially interesting (QD SL) Ongoing CTs by BMS

9. Medicines Patent Pool – Strictly Confidential, Not for Circulation Role of Stakeholders ProblemSolutionDrugStakeholders involved IPNegotiate in- and out-licences LPV, RTV, DRV, RAL, ETV; TAF, DTG, ATV (being negotiated) MPP, ORC, Gx Technology Usual: ORC  Gx (future: Gx  Gx?) Financing to speed the process? All will be DDS based formulations ORC, Gx, MPP, CHAI? Catalytic partners s.a UNITAID? Dosing Specific recommendation on dosage ratios FDCs esp. those containing TDF, DTG, DRV, ATV WHO Market size Guidelines & forecasts: help stimulate market and product development; Catalytic financing to create market for a new formulation New guidelines will help improve certainty; Forecasts by formulation and for new ARVs – still a gap WHO? UNAIDS? CHAI? Major purchasers (UNITAID/GFATM/PEPF AR)? GF Paed ARV PWG Clinical Trials for FDC Financing and coordination of clinical trials for new FDCs Financing: UNITAID? NIH? EDCTP? BMGF? Technical: DNDi? Coordination required between several stakeholders; Treatment uptake in particular community involvement will be key Coordination required between several stakeholders; Treatment uptake in particular community involvement will be key

10. Medicines Patent Pool – Strictly Confidential, Not for Circulation Thank You