David Cram, Pharm.D.Associate Director, MSL Program

GenentechPLEASE NOTE THAT THESE ARE MY VIEWS AND NOT NECESSARILY

THOSE OF GENENTECH

Mid 1980’s Three or 4 small groups in the US Focus of most groups on company sponsored

trials Funding originating from development or

transferred to development 1990’s

Rapid growth in MSL teams Focus changed to Post-Marketing activities Warner-Lambert Case—MSL becomes

household name

Early 2000’s Growth slowed (although demand still high) External regulations begin to be strictly

enforced Continued heterogeneity of groups as

companies redefine structures under enforced guidelines

Current status Internal company regulations grow with

attention on field-based MSL groups MSL teams find it difficult to justify their costly

existence with only metrics of call volume and other post-marketing deliverables

MSL teams are asked to “do more with less”

Focus is specifically on Post-marketed (PM) projects whose charge is specifically to provide on-label speaker training, develop advisory boards, provide inservices, and be “conductors” for thought leader development—Report to Commercial

Focus is specifically on Clinical Development projects related to clinical trials and Investigator Sponsored Trials (ISTs) and Investigator development with limited focus on Post-Marketing activities—Report to Clinical Development

Work with Clinical Development to design appropriate clinical trials

Work with Clinical Development on Clinical Advisory Boards

Identify and maintain corporate relations with investigators in both academic and community settings

Be eyes and ears for competitive development programs and/or changes in clinical dogma – provide information to Clinical Development Teams

Assist with clinical trial enrollment Support investigator sponsored trials (ISTs) Field clinical questions and issues

Act as the Medical Director in the Field

Corporate goal is to develop a clinical trial to treat Toe Nail Cancer and have the trial completely enrolled in two years.

Note: This trial will be used to expand the indication for this molecule.

MSL Team Develops a Plan by: Surveying specific toe nail oncology

specialists to gain feedback on the overall concept and ideas for trial development and to report findings back to the Clinical Development Team

Creating an intervention plan that will focus on top accruing investigators to gain support for trial participation and present to the Clinical Development and Operations Teams

MSL Team Executes Plan by: Gaining acceptance by medical investigators

who enroll patients for the trial Continuing to call on high enrolling sites to

maintain their interest and provide support Identifying struggling sites, meeting with

them, helping find solutions or recommending to shut them down*

* It costs money to keep sites on the books

Metrics Study completes earlier than expected Indication for this molecule is accepted by

FDA 4 months earlier than predicted Company has determined that every day the

molecules is used for this indication brings $500K per day (or $60 million over 4 months)

A new molecule in Phase I shows good safety results. The goal is to bring this drug to later phase trials in Newest Disease Syndrome (NDS) over the next two years. This is a new therapeutic area for the Company. *

* Note: Three other companies are identified to be developing molecules for NDS. The Company is uncertain of the current status of the competing molecules but believe that their competitors are ahead of them. Critical “Go/No Go” decision will be based upon the the Company’s development strategy vs. its competitors.

MSL Team Develops a Plan to: Identify investigators who focus specifically on

NDS by utilizing existing relationships with other related investigators

Develop relationships with these investigators and bring knowledge in-house on regular Clinical Development-MSL calls

Identify key issues in NDS and specific issues with executing human trials in this area

Stay abreast of CI related to other competing molecules in development at major meetings, on investigator calls, investigator meetings, web, etc.

MSL Team Executes Plan by: Identifying key research sites with specific

capabilities to participate and enroll NDS patients into study QUICKLY (e.g. patients not tied up in competitor trials, etc.)

Continuing to foster solid relationships with key investigators/experts in NDS by regular involvement of them in key decisions such as getting feedback on trial design and Life Cycle Management

Bringing back valuable information about study updates, study enrollment, NDS environment, and current practice standards to in-house teams (e.g. Clinical Development and Clinical Operations)

While Executing the Plan, the MSL Team Discovers that: In early-on meetings with investigators, only

one competitor is actually far enough along to be of significance -- that they are 1 year ahead. However, the competitor has had some early safety warnings related to patients with concomitant Oldest Disease Syndrome (ODS). All other patients did well.

Critical and Strategic Recommendation Made by the MSL Team: Exclude patients with concomitant ODS from

clinical trial development program (up to 25% of the population)

Metrics Company completes Phase II and III program in record

time showing excellent efficacy and very acceptable safety profile on their NDS Molecule – 1 year ahead of projected time

Program hailed by top thought leaders in NDS as brilliant and very well executed

Drug expected to bring in a revenue of $300 million in first year of launch

Total drug development costs lower than expected at $400 million (vs. $600 million)

Company drug surpasses nearest competitor by 2 years MSL Team voted “Best in Class” by NDS Health Care

Professionals

Heftycore®, a novel blockbuster molecule for Blabbermouth Disorder (BMD), has done well in this indication both from a patient/provider satisfaction standpoint and financially

MSLs have discovered through working with their IST investigators that Heftycore® may also have benefit in Irritating-People-On-Planes Syndrome (IPPS)—A huge market.

Company does not see how current MOA will fit for IPPS as the affinity is weak for IPPS receptors in the brain and higher dosages may be required which would cause increased side effects.

MSL Team Develops a Plan to: Gather more information from current

investigators and current literature in IPPS to support MOA for Heftycore®

Ask for analyses of data of early trials using Heftycore® in IPPS from IST investigators and prepares presentation to Company as to which patients might most benefit

Outline potential company sponsored, label-enabling trial to Clinical Development team

MSL Team Executes Plan by: Organizing a meeting between Investigators

and Clinical Development team through an Advisory Board to present findings and plea to pursue this study

Proposing an outline for registrational study which is accepted and executed

While Executing the Plan, the MSL Team Discovers that: Upon analysis of early trials (e.g. ISTs and case

studies) and discussions with investigators, that there is viable MOA support for Heftycore® in IPPS.

Findings show patients with IPPS and a concomitant disease known as Oversized Bag Complex (OBC), a back breaking disorder in about 35% of IPPS patients, will benefit from this Molecule and can tolerate the higher doses required

Critical and Strategic Recommendation Made by the MSL Team: Design study to analyze patient with IPPS + OBC

Metrics Market for use of Heftycore® in IPPS will be

at least $250 million in additional annual revenue with approved label promotion

Study shows Heftycore® in patients with IPPS and OBS, higher doses is both efficacious and safe -- FDA grants label

The new indication extends patent life of Heftycore® by 2 years

Over the remaining patent life of Heftycore®, IPPS indication garners additional $1 billion in sales for company

MSL teams can be significant contributors to the clinical drug development process (e.g. better designed trials, earlier time to market, decreased development costs, etc.)

A shift to drug development activities from traditional 1990’s MSL PM activities can add value to a company’s bottom-line with less risk in today’s regulatory environment

A strategic role in drug development offers objective and measurable metrics to justify team existence and headcount

MSL teams involved in drug development are often more connected and satisfied with their jobs

Training of MSL Teams into a Clinical Development role may require a paradigm shift from current post-marketing focused roles

Depending on lifecycle of a molecule, Post-Marketing activities is still an important role for the MSL Team, however, many companies miss the critical impact of MSLs involved in clinical drug development

Physician issues Lack of financial incentive

Competitive Marketplace

Alignment of PI and Study Coordinator expectations

SOPS with research referrals and/or unfamiliarity with research

Patient logistics Distance to study sites

High cost of gasoline

Congested traffic areas

Number of study visits

MSL issues Limited access and/or familiarity with area PCPs and their office staff

Short-time frame for success when MSLs brought in

Update

MSLs Early involvement in the Recruitment Process

Involve Study Coordinators or internal GNE person to track patient origination for ROI

Sites where MSLs have working relationships seem to produce better results (e.g., CIU telephone survey)

Study Coordinators Outreach to follow-up with sites visited by MSLs

Minimal workload studies yield better patient recruitment

Sites Work with the PI and study site to obtain a list of referral PCP for targeted MSL

visits

Update

Solid basic science foundation Strong clinical acumen Business literacy Exceptional people skills Individual discipline Anticipating needs Flexible

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