Jurek BojanowskiPharm D – Clinical Operations Lead

Boston, 15 July 2015

Oncology phase 1 study conduct under the Alliance Partnership with Quintiles

EMD Serono – A Subsidiary of Merck KGaAin Darmstadt, Germany

SCOPE Summit 20152

Merck KGaA, Darmstadt, Germany is the oldest pharmaceutical and chemical company in the world, founded in 1668

Merck Serono is the biopharmaceutical division of Merck KGaA

We operate under the nameEMD Serono in North America

What will be discussed

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Overall benefits of an End-to-End Operating Model

Study Team Composition and Governance

Roles and Responsibilities within the Joint Team

Site Selection Process, Medical Monitoring in Phase I Oncology Studies

EMD Serono – Quintiles Partnership

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In 2013 EMD Serono has signed a strategic-level deal with Quintiles

Quintiles became part of the R&D fiber at EMD Serono and makes it the sole outsourcing partner for clinical trials design, planning and execution from phase I through to post-marketing studies.

The EMD Serono-Quintiles relationship combines the skills and expertise of both companies to enhance the productivity of the EMD Serono pipeline by bringing Quintiles efficient and predictable operational delivery into the development process.

EMD Serono and Quintiles operate as one team for the design and execution work of clinical trials.

Mutualism: A relationship where both species benefit from the relationship

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Overall benefits of an End-to-End Operating Model

Innovation: Leverage leading and cutting-edge solutions that drive productivity through alternate approaches to technology, process, and/or resourcing

Efficiency & Productivity: Define and implement standardized, streamlined processes for reliable and efficient operational delivery, and increased productivity; eliminate redundancies for consistent development efforts to maximize the value of the development pipeline

Transparency: Team together to exchange information, ideas and concerns in a clear, transparent manner where trust-based relationships are built and flourish

Aligned Roles & Responsibilities: Lean on the strengths of each organization to enable resource efficiency where EMD provides robust oversight and our partners drive execution of operations

Shared & Predictable Financial Accountability: Collectively generate measurable costs savings that deliver on savings and efficiency targets 6

Three Principle Pillars

Sole Primary Provider

Relationship

Early Engagement

& Collaboration on Planning and Design

Joint Accountability

for Success

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End-to-End – Quintiles early involvement in Clinical Planning & Design

Quintiles participation in EMD Serono Committees

Core & Dedicated Partnership Resources in Key Functions

Transparent commercial model and

operational targetsConsistency

Deeper relationships

Continuous improvement

Strategy & Planning Execution

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What makes the EMD Serono – Q Partnership unique & different : Trust & Transparency

Quintiles as sole primary providerHigher and more predictable volumeEasier alignment on processes and standardsSimplified IT systems landscape

EMD Serono - Drives and owns clinical strategyQuintiles - Provides input and operational thinking into strategy

To define the clinical development operating plan

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The Partnership Operating Model

EMDSerono - Focus on effective oversight (outcomes vs. process)Quintiles - Responsible for end-to-end trial execution & results; leveraging SOPs and systems

To deliver excellent trial execution & results

The Partnership Operating Model

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Alignment of Governance & Activities

Day to Day Operations & Activity

Daily, Weekly, As Needed

Ongoing Delivery of R&D Projects,

Program, Trials by Teams

Delivery Forum (PDF)

Quality Council (PQC)

Finance Forum (PFF)

Partnership Leadership

Committee (PLC)

F nctional & Regional

Liaisons

Functional & Regional Interaction (EMD Serono & Q) –

LiaisonsM

onth

ly P

artn

ersh

ip L

eads

Tou

ch P

oint

(PLT

P)

Executive Steering Committee (ESC)

Portfolio Delivery & Continuous Improvement,

Oversight, Escalation

Monthly +/-

Partnership Optimization, Strategic Planning, Sponsorship

for Continuous Improvement &

Innovation Initiatives

4X Per Annum

Partnership Evolution, Corporate & Capital

Investment

Bi-Annually

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Clinical Trial Team Composition –Key Members

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Clinical Operations Team(COT)

Clinical Operations Lead (COL)

Clinical Trial Lead (CTL)

Clinical Data Sciences

Safety

Ad hoc participation:• Regulatory• Medical Writing• Clinical Trial Supplies• QA• Procurement• ...

Clinical Trial Coordinator

Medical

Clinical Trial Lead / Q Project Manager

CTL

Monitoring Team / Region based resources

BiostatClinical Trial Team (CTT)

Clinical Trial Team

Q Program Director

Mirror Quintiles / EMD Serono Teams at CTT

Quintilesrepresented by Q Program Director at COT

Roles & Responsibilities in a Study Under Partnership Strategic Partnership Manual provides operating principles required to conduct the study in a seamless way

Included are objectives, governance, KPI, flow of interactions and RACI

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EMD

EMD

E.g. of flow for Trial Team Kick Off Meeting organization

RACI

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RR Responsible The doer

AA Accountable Liable for activity

CC Consult In the loop

II Informed Keep in the picture

Roles & Responsibilities in a Study Under Partnership

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EMD

EMD

E.g. of a RACI table for Trial Team Kick Off Meeting organization

Roles & Responsibilities – Early Stage Studies

A more complex RACI…

Roles & Responsibilities in Ph1 Oncology Trials – Examples

Site identification / selectionInvolvement of KOLs – strategic purpose

Involvement of High recruiting sites– Consensus needed between EMD Serono and Quintiles

Dose escalation decisionDriven by the existing Merck Serono Work Instructions on the constitution and handling of the Study Monitoring Committee (SMC), however :

SMC voting members– Principal Investigator

– Quintiles Medical Lead

– EMD Serono Medical Trial Lead

– EMD Serono Global Drug Safety Representative

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Roles & Responsibilities in Ph1 Oncology Trials – ExamplesMedical Monitoring support is part of the Quintiles Medical Services and includes:

Reviewing the protocolProviding input into feasibility

Providing medical input into site identification

Providing input into the CRF design

Preparing this Medical Monitoring Plan

Provision of general medical input into trial quality and safety

Providing medical monitoring (supporting and addressing questions of the sites) 24h/7 days coverage

Medical Review

Generation of medical queries with follow-up to their resolution

Provide review of the Clinical Study Report

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Roles & Responsibilities in Ph1 Oncology Trials – Examples

Anticipated optimization of the documents

Risk of divergent opinions

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“Operational” medical support expected from Q Medical

“Strategic involvement” expected from EMD Serono Medical representative

In real life – mix of both happening

Joint Quintiles / EMD SeronoProtocol (and Concept Sheet)

review:

Providing medical monitoring (supporting and addressing

questions of the sites)

Between expectations…

Any investigator request to contact the

medical monitor for an urgent reason will be sent directly to Quintiles Trial

Medical Advisor (TMA).

Based on prior site relationship

and issue discussed, the

TMA may involve the EMD Serono physician in the site contact, or

contact site directly.

The Quintiles TMA will

document the site contact in an

email copying the CRA and

CPM. A summary of site contacts will be added to the study

Q&A log.

…and reality

(sites do often contact Sponsor Medical Lead first):

The EMD Seronomedical lead will

keep the TMA informed of direct

medical discussions with

study PIs to ensure adequate

communication within the team.

Information should include date of

contact and issue discussed, and will be forwarded to the

Clinical Project Coordinator for inclusion in the study Q&A log.

How do you get Teams to think about what the future could be, in a way that inspires them and continues to spark action, but also takes into account the simple fact that the future is unpredictable?

Anonymous

Moving forward with Alliance

By addressing early challenges

Transition Phase– Initial resistance and lengthy period of transition

Behavioral Shifts– Moving from the “Master-Servant“ mindset to the “Proactive“ and

recommend behaviors within Q

– Be patient – people will revert to what is familiar and comfortable

Culture is as important as strategy & execution– Maintain an environment when “Change Agents“ can thrive

Refocusing on Partnership benefits & desired outcomes

1 Measured in satisfaction survey

Benefits of Strategic Partnership

Beating industry benchmarks for timelines and costs

Higher productivity - funding more projects with same budget

Improving expected vs. planned enrollment rate

Improved predictability of development cost and timelines

Support R&D ambition to achieve launching new medicines every year

Higher probability of successthrough increased focus on more promising compounds

Year-on-year improvement in employee satisfaction1

Clearer roles & accountabilities and more satisfying jobs

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Example Expected Outcomes

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Conclusions

EMD Serono / Quintiles partnership is evolving successfully to develop new treatments within optimized budget and timelines.

Devil lays in the details; in execution of activities, interpretations of roles & responsibilities especially for complex trials.

Lessons learnedMindset changeUpdates to processes, Partnership manual Understanding of the benefits of our mutualistic relationship, for Quintiles, EMD Serono but especially for Patients.

Continuous improvement through :