MEETING SCHEDULED on July 6th

At this meeting we will discuss the consultancy service requirements as was done with CRS (see
below).

Dear Edwin ,

Could we plan a meeting to discuss with your team our request by the end of this week ? Ill send you
the synopsis of our study and our questions before the meeting.

The objective of the meeting is to discuss the possibility of receiving the consultancy services for the
phase IV adhesion study synopsis finalization from the QPS team. This consultancy service will be
separated from the Invitation to Tender for the study. After this, Pierre Fabre will create a Request
For Proposal for the conduct of this study.

Please find below the questions we would like discuss about your expertise in the patches
adhesiveness studies :

How many studies QPS performed in the previous 5 years with the patches (including the
number of studies with NICOTINELL), especially for the adhesiveness ,
QPSs experience in adhesiveness studies having used the FDA and EMEA adhesiveness
guidelines,
Previous experiences with study in the real life condition (sport exercise, shower)

From our side we will present to our team the study context and which expertise / advice we need.

Do not hesitate to contact me in case of the questions,

I am not available tomorrow.

Kind regards,

MINUTES with CRS

Dear all,

Thank you for your participation to our meeting on June 9th regarding the Nicotine patchs study.
Please find below the minutes and the next steps.

Attendees from CRS: Physician Dr. Bettina Nowotny , Project Manager Stephanie Cremer, Director
Business Development Nannette Ficher

Attendees from Pierre Fabre : Victoria Dauphant Clinical Program Director , Marlne Guiraud -
Clinical Operation Manager, Zaim Mohammed - Clinical study Physician, Nadine Harambillet - Project
Manager, Edith Carriere Roussel - Clinical study Manager

The objective of the meeting was to discuss the possibility of receiving the consultancy services for
the phase IV adhesion study synopsis finalization from the CRS team.
This consultancy service will be separated from the Invitation to Tender for the study. After
this, Pierre Fabre will create a Request For Proposal for the conduct of this study.

During the discussion, CRS presented their experience with dermal treatment investigation :
TTS/TDS, LST, skin irritation, phototoxicity, photoallergenicity, etc. with some studies with nicotine
containing products. For our information, CRS will send us the information sheet specific to their
experience with the transdermal patches. We are interested to know :

How many studies CRS performed in the previous 5 years with the patches (including the
number of studies with NICOTINELL), especially for the adhesiveness ,
CRSs experience in adhesiveness studies having used the FDA and EMEA adhesiveness
guidelines,
Previous experiences with study in the real life condition (sport exercise, shower)

The objective of the study is to assess an adhesion of V0116 21 mg/24h transdermal patch
compared to the NICOTINELL TTS 21mg/24h transdermal patch after a single application in healthy
smokers.

Study context :

A MA was already granted fort the patch V0116 21 mg/24h. So the requested study will be a phase IV
study. The studys results will be used for the marketing communication. The current market of the
PFs patch is Europe. However, a further commercialization of our patch in the US is not excluded.
So, in this context could you please advise us which Guideline would be better to use, in particular
for the choice of the primary efficacy criterion: FDA or EMEA grading scales? In your opinion, is
there the possibility to design a study that comply with the 2 guidelines?

In this context , we need your advice on the following questions :

Study Design: regarding that it is not a study for MA, we dont need to demonstrate
the non-inferiority of V0116 vs NICOTINELL. We need to perform a study to compare
the patches. In this context , we would like to compare the adhesiveness qualities of
V0116 21 mg/24h transdermal patch in real life conditions to the NICOTINELL TTS
21mg/24h transdermal and we expect to demonstrate the superiority of PFs patch
on the primary criteria (adhesiveness) and on the better subjects acceptability (
aesthetic qualities, comfort , etc).
Sample size : Regarding context of the study, how many subjects will be needed to
enroll? For sample size calculation, what could be the optimal hypothesis to be
tested? According to your experience, what is the probability to achieve this goal
with NICOTINELL as reference? With which guideline we need less subjects to enroll?
Definition of the optimal evaluation time-points which could discriminate the
patchs adhesive performances.
Real life conditions : advice on the activities type and schedule during the day with
detailed information about the standardization of such activities.
Which guideline : EMEA or FDA ? With which guideline we have more chance to
differentiate the patches ? Regarding your previous experience with the patches ,
how often you had observed the differences between products?
Advice on the application area and application time . Do we need to diversify the
application time of the patches and create 2 subgroups : morning and evening
applications? Does it make sense?
 Subjects perception (satisfaction, acceptability and preference questionnaires): what
is your experience in this field ? Any advice on the appropriate perception
questionnaires to be used that could differentiate from NICOTINELL?

Next steps :

Pierre Fabre: send to CRS the consultancy agreement which will cover the synopsis advice
and writing and the meetings related to this request. Done
CRS : send us the comments on the consultancy agreement
CRS : send us the budget and time lines proposal regarding the above request after the
reception of this e mail
Pierre Fabre : approve the CRSs budget and timelines proposal
Pierre-Fabre and CRS : sign the contract before the end of June 2017

Deadline: regarding the urgency of this request, we expect to finalize the offer on week from June
19th to 23th . We kindly ask you to give us your feedback whether this deadline seems realistic for
you.

Kind regards,

Victoria