Utilization of Drug Pooling to Optimize Complex Drug

Utilization of Drug Pooling to Optimize Complex Drug Management Kevin Collier, Sr. Director Product, Rave RTSM kcollier@medidata. com Blair Grimes, Manager Supply Chain, Dermavant blair. grimes@dermavant. com

Agenda ➢ Trends of interest ➢ What is drug pooling? ➢ Benefits of pooling? ➢ How can technology help overcome opposition? ➢ Case Studies ➢ Summary of Benefits © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 2

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 Ph 3) Increase interest to better plan clinical supply needs through forecasting, improved utilization, more efficient supply chain © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 3

What is “pooled supplies? ” Sharing the same lot across multiple trials Depot 2 Depot Pooled Group Non-Sharing Study Supplies are associated to a trial at the time a packlist is uploaded Non-sharing study Study 1 Depot 1 Study 2 Depot 2 Study 3 Depot 3 Lot 1 Lot 2 Lot 3 Site 1 Site 2 Site 3 Depot 1 15 Study 1 Study 2 Study 3 Lot 1 Sites Site 1 Site 2 Site 3 Depot Pooled Group Supplies are associated to a trial at time of shipping Site Pooled Group Supplies are associated to a trial at time of dispensation Site Pooled Group Depot 1 Study 2 Study 3 Lot 1 Site 1 Subjects Subj 1 Subj 2 Subj 3 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 4

Benefits of Pooling Average Supply overage in studies today ~30% per trial Program without pooling 4 trials in a program Manufacture 1000 kits for each trial • Total manufactured (4 x 1000 = 4000) • Wasted kits (30% x 4) = 1200 Program with pooling If running simultaneously: • Forecasted need = 2800 kits • Spread supply buffer across all trials ○ 3700 manufactured (2800 + 30% = 3640) • 300 less kits and reduction in waste If running concurrently: • 1000 manufactured for first trial • Roll over 300 left-over, etc… © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 5

Let’s look at technology in action! 6 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 6

Remove Technology as a Barrier Technology can help foster adoption Operational and Regulatory Oppositions • • • 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? New Technology Paradigm • • • 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 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 7

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 Solution for the site • Receive one shipment Burden for depots • Pick, pack and ship multiple shipments all going to same destination Solution for depot • Pick, pack and ship one combined shipment to the site Burden for sponsor • Pay for multiple shipments instead of one: increase drug overage for each database: increase in drug waste? Solution for sponsor • Run multiple indication databases with less inventory • Decrease costs by sharing supplies across studies and sites 8 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 8

Case Study: Mid-sized biotech with innovative immuno-oncology treatment Challenges ● ● 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 Clinical Strategy ● ● 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 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 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 9 9

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. © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 10 10

Here is another Sponsor perspective Blair Grimes Manager Supply Chain, Dermavant blair. grimes@dermavant. com © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 11

Dermavant Use Case Pooled supplies allows for a single label Phase III Study: Protocol #1 Study Details: ● ● ● 2 x Identical Phase III Studies rolling into a single long-term extension study Psoriasis Topical Formulation US and Canada Single Label across all 3 studies 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 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 12

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 Individual Study Overages Minimum Maximum Study Overages Study Drug Calculation (tube per patient per week): 2 Tubes 3 Studies © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 13

Why Drug Pooling with Medidata’s RTSM? Benefits ● ● ● 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 Impact ● ● ● 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) 14 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 14

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 © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 15

Summary Let’s move Drug Pooling from a concept to a substantive usage rate ● There 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. © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 16 16

Questions? For more information: Kevin Collier, Sr. Director Product, Rave RTSM kcollier@medidata. com Blair Grimes, Manager Supply Chain, Dermavant blair. grimes@dermavant. com © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 17

Thank you © 2019 Medidata Solutions, Inc. – Proprietary and Confidential 18

Sources Clinical Development Success Rates 2006 -2015 Tufts Center for Study of Drug Development Cost to Develop New Pharmaceutical Drug Now Exceeds $2. 5 B 19 Solutions, Inc. – Proprietary and Confidential © 2019 Medidata 19