1. Utilization of Drug Pooling to Optimize Complex Drug Management
Kevin Collier, Sr. Director Product, Rave RTSM
Blair Grimes, Manager Supply Chain, Dermavant

2. Agenda Trends of interest What is drug pooling? Benefits of pooling?
How can technology help overcome opposition?
Case Studies
Summary of Benefits

3. Broader Trends in Clinical Studies
Cost of bringing new drugs to market continues to increase
Companies continue to search for efficiency gains in all aspects of R&D
Timelines continue to be a challenge and Sponsors are looking for ways to shorten these
Reduce Costs; Maintain Quality!
Truly global studies are growing in scope and breadth
Study complexity increasing (combining phases, planned changes)
Logistics are becoming more complex
Increasingly focused on biologics
Expensive to manufacture
Often limited in supply
Oncology is predominant therapeutic area; higher failure rates, (especially in Ph3)
Increase interest to better plan clinical supply needs through forecasting, improved utilization, more efficient supply chain
Increasingly focused on biologics
Expensive to manufacture
Often limited in supply

4. What is “pooled supplies?”
Sharing the same lot across multiple trials
Depot 2 15
Depot 1
Study 1
Study 2
Study 3
Lot 1
Depot Pooled Group
Sites
Site 2
Site 3
Site 1
Non-Sharing Study
Supplies are associated to a trial at the time a packlist is uploaded
Site Pooled Group
Supplies are associated to a trial at time of dispensation
Depot Pooled Group
Supplies are associated to a trial at time of shipping
Increasingly focused on biologics
Expensive to manufacture
Often limited in supply
Study 1
Depot 1
Lot 1
Site 1
Study 2
Depot 2
Lot 2
Site 2
Study 3
Depot 3
Lot 3
Site 3
Non-sharing study
Subjects
Subj 2
Subj 3
Subj 1
Depot 1
Study 1
Study 2
Study 3
Lot 1
Site Pooled Group
Site 1

5. Program without pooling
Benefits of Pooling
Average Supply overage in studies today ~30% per trial
Program with pooling
Program without pooling
4 trials in a program
Manufacture 1000 kits for each trial
Total manufactured (4x1000 = 4000)
Wasted kits (30% x 4) = 1200
If running simultaneously:
Forecasted need = 2800 kits
Spread supply buffer across all trials
3700 manufactured ( % = 3640)
300 less kits and reduction in waste
If running concurrently:
1000 manufactured for first trial
Roll over 300 left-over, etc…
These are general advantages of pooling. More specific examples are coming up in later slides (Tesaro)

6. Let’s look at technology in action!

7. Remove Technology as a Barrier
Technology can help foster adoption
Operational and Regulatory Oppositions
New Technology Paradigm
Foreknowledge of trials
Cost and effort of pooling systems
Drug Accountability
Labeling (US vs ex-US)
Ability to map sites across trials
Lack of transparency to inventory levels
Un-numbered supplies work around?
Pooling benefits determined after trial/program start
Configurable solution instead of customized
Site’s drug accountability activities are transparent across trials
Share at the lot level rather than the study level
Inventory transparency in system and through robust reporting
Platform allows for program and portfolio level metadata

8. Solution via Pooling at Site
Logistical Challenges and Solutions
Technology can help mitigate challenges
Challenges
Solution via Pooling at Site
Burden for the site
Receive multiple shipments of drug into different databases
Burden for depots
Pick, pack and ship multiple shipments all going to same destination
Burden for sponsor
Pay for multiple shipments instead of one: increase drug overage for each database: increase in drug waste?
Solution for the site
Receive one shipment
Solution for depot
Pick, pack and ship one combined shipment to the site
Solution for sponsor
Run multiple indication databases with less inventory
Decrease costs by sharing supplies across studies and sites
Applying configurable solutions vs programmed/customized solutions
Traditional paradigm of programmed solutions add prohibitive cost and lead time to build and test
Accountability and reconciliation activities must be transparent to Site Managers across all studies
Provide robust reporting
Essential for forecasting and accountability
Flexibility to handle inevitable uncertainties
What trials will utilizing pooling? When will they start?
Allow studies to be added dynamically
What supply will be pooled?
Allow new drug to be added
Allow new lots to be created
Allow for mix of pooled and non- pooled
Enable protocol specific labeling at time of shipment
Trials using pooled supplies are costly and time consuming to implement
Lots and items must be identified ahead of time so they can be programmed to be pooled
Ancillary supplies are in a common pool and it’s hard to know precise charges for each trial
Balance Benefits:
Pooled Groups can be created anytime, even after a trial goes live
New lots can be added to a pooled group anytime
Any type of article can be added to Pooled Groups, so precise usage can ascertained
Elevator Pitch:
Since Balance is a configurable system, pooling can be set-up in a matter of minutes, not months. There is no additional Rave work required for trials to be part of a pooled group. 8

9. Case Study:
Mid-sized biotech with innovative immuno-oncology treatment
Challenges
Clinical Strategy
Early stages of development, not sure what indications benefit the most
Needs to simultaneously investigate 5 tumor types
Treatment schedules varied
Data collection varied
Large molecule: scarce and expensive to manufacture
Sites included many ‘megacenters’ enrolling across multiple patient groups
Part I dose finding escalation
Part II investigation of multiple tumor types at MTD
Many unknowns and changes occurring throughout the life of the study
Execute in manner that preserved the science while optimizing the timeline and budget
TESARO had an adaptive design protocol, which included the investigation of multiple tumor types with many unknowns and changes occurring throughout the life of the study
To handle the tumor specific changes in the quickest fashion, it was decided to split the study build into tumor specific databases (in Rave and Balance)
The best approach from a scientific perspective brought operational challenges
How to handle tumor specific changes and addition of cohorts in the quickest fashion?
Multiple databases being used simultaneously at the sites to study the same treatment - inherently inefficient from a supply perspective 9

10. Case Study Outcomes: Pooled Supplies
Mid-sized biotech with innovative immuno-oncology treatment
Agile constantly changing trial design and stable supply management
Sponsor estimates 39% less package waste and a 34% reduction in shipping costs by applying the pooling strategy
Achieved without making compromises to the (complicated) study design and clinical objectives dose finding escalation
Study is ongoing and operating smoothly. 10

11. Blair Grimes Here is another Sponsor perspective Manager Supply Chain,
Dermavant

12. Study Details:
2x Identical Phase III Studies rolling into a single long-term extension study
Psoriasis
Topical Formulation
US and Canada
Single Label across all 3 studies
Dermavant Use Case
Pooled supplies allows for a single label
Phase III Study: Protocol #1
Long-Term Extension:
Protocol #3
Phase III Study: Protocol #2
Pooling all supplies for two identical Phase III studies and a long-term extension allows for a single label

13. Unique Challenges for Topical Formulation
Study drug estimates are based on average Body Surface Area Percentages (BSA%)
Number of tubes must be rounded-up to nearest full tube
Overages are applied based on a high BSA% and full tubes
Disease Severity Determination for BSA%
Average Tubes per Patient per week:
1.3 Tubes
Study Overages
Individual Study Overages
Minimum
Maximum
3 Studies
Study Drug Calculation (tube per patient per week):
2 Tubes

14. Why Drug Pooling with Medidata’s RTSM?
Benefits
Impact
No need for separate supplies for each study
No need to re-seed sites for the extension study
Easier to manage supply with a single source of drug supply across all studies
Flexibility to move IP from one study to another without re-labeling if there is a need in the future (non-enrolling sites, over supplied sites)
Hope to gain back rounding errors and reduce total amount of tubes required to supply the study
Expect to reduce the need for final packaging run/ manufacture addition drug product batch
Expected Cost Savings from reduced packaging runs (reduced number of batch records and total number of kits)
Expected Cost Savings with reduced shipments
Reduce study overage requirements (hoping to apply to future studies to reduce upfront manufacturing)
Topical formulations create uncertainty with the amount of drug required per subject
Challenges in forecasting topical formulations:
Ability to use “per patient per tube” calculations, but consistently rounding up to whole tube
Calculations based on above average severity, resulting in over supply 14

15. What is Dermavant looking to achieve?
Make the best use of the supply
Achieve maximum flexibility with current inventory
Reduce study drug overages
Reduce cost of packaging and labeling

16. Summary
Let’s move Drug Pooling from a concept to a substantive usage rate
There are added challenges yet inherent value to pooling the supplies – especially as IP becomes more expensive and innovative approaches are applied to trial design.
Advancements in IRT/RTSM technology can reduce operational complexities, allowing sponsors to realize the value of implementing pooling strategies.
Challenge to audience:
Shift from tactical/incremental improvements - Push boundaries and bring strategic innovation to trial supply management. 16

17. Questions? For more information:
Kevin Collier, Sr. Director Product, Rave RTSM
Blair Grimes, Manager Supply Chain, Dermavant

18. Thank you

19. Sources Clinical Development Success Rates 2006-2015
Tufts Center for Study of Drug Development
Cost to Develop New Pharmaceutical Drug Now Exceeds $2.5B