PO executive summary 2015-2016 260115

Orientation Plan 2016/2017 Country: Central America and the Caribbean

The doctor does not see the need to provide more energy to the ischemic heart, so do not see the
importance of using Vastarel MR in the treatment of angina.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

3. ORIENTATION

3.1. Strategic goal

Highlight the importance of energy supply for the ischemic* patient, demonstrating the powerful
anti-anginal and anti-ischemic efficacy of Vastarel MR, because of its unique improvement of
energy to the ischemic heart.
*angina, post MI, HF, diabetics, pre/post revascularization

3.2. Promotional axis and main messages

Vastarel MR is essential for your ischemic* patients because of its unique improvement of energy to
the ischemic heart leading to powerful anti-anginal and anti-ischemic efficacy.
*angina, post MI, HF, diabetics, pre/post revascularization

Main messages
 There are multiple patients suffering ischemia, such as angina, post MI, diabetics, HF, pre/post

revascularization patients.
 The energy plays an important role in the ischemic heart disease.
 Vastarel MR provides a powerful anti-anginal efficacy thanks to its unique improvement of

energy to the ischemic heart.
 Vastarel MR increases the exercise capacity, resulting in better quality of life for the ischemic

patient.

3.3. Operational strategy (main strategic orientations in term

of media mix)

 Detailing scheame / Visual aid :
It’s going to be orientated in the message: Vastarel MR is essential for your ischemic patients
because of its unique improvement of energy to the ischemic heart leading to powerful anginal and
anti-ischemic efficacy.

 Leave pieces:

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

 Brochure: Ischemic heart disease in practice: ” Cardiomyocyte energy crisis as a core treatment
target for patients with coronary artery disease”

 The Vastarel MR word Tribune: “Increasing cardiac energy brings benefits in ischemic patients”
 Clinical cases focus in angina patients with diabetes and angina patients before, during and

after revascularizations.

 Round table:
Slide set with the message “The important role that energy plays in ischemic heart disease and the
powerful anti anginal and anti-ischemic efficacy of Vastarel MR”.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

4. APPENDIX

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

O PRIENTATION LAN 2016 / 2017

Central America and the Caribbean

Product: Procoralan

PROJECT MANAGER: Giovanni COLUCCI

TO 854,420 Evolution (%)
Unit 39,388 +13
+11
Contribution to 5.4%
subsidiary TO

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

Contents

1. SUMMARY ..................................................................................................................... 14
2. PRODUCT POSITIONING ............................................................................................. 16

2.1. Key figures ............................................................................................................. 16
2.2. Perceived product image ...................................................................................... 22
2.3. Perception of competitor products ...................................................................... 23
2.4. Feedback on product promotion .......................................................................... 24
2.5. Key environment-related facts.............................................................................. 26
2.6. Expected key items related to the product .......................................................... 27
2.7. SWOT analysis ....................................................................................................... 28

2.7.1 Strengths/Weaknesses - related to the product ............................................ 28
2.7.2 Opportunities/ Constraints -Threats - related to the environment............... 29
2.7.3 Diagnosis .......................................................................................................... 29
3. ORIENTATION............................................................................................................... 30
3.1. Strategic goal ......................................................................................................... 30
3.2. Promotional axis and main messages ................................................................. 30
3.3. Operational strategy (main strategic orientations in term of mediamix) .......... 31
4. APPENDIX ..................................................................................................................... 32

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

1. SUMMARY

Procoralan represents 5.4% of the total Market share of the subsidiary in TO ranking N°6.
At the end of our financial year we finished with 854,420 USD, with a growth of +13% in TO
and 39,388 units with a growth of +11% in private sales.
In total local sales we finished in 19,907 standard units with a growth of 16% and most of
our sales, 63%, coming from Procoralan 5mg.

Market and Sales breakdown
In the symptomatic CAD market: we have in C07A, beta blockers, the main important class
with 43% MS with a growth of +5%, that’s mean a great opportunity to grow up more
especially when Procoralan´s promotion is related to combine it with them and C01D class
is decreasing by 3%.
In the HF market, the C03A class shows the greater dynamism among all the classes with
+6% of growth and with 25% of the market share, but beta blockers, C07A, has the main
market share with 40%.

The HF Market growth by
MAT 6.2 / QTR 3.1

Beta Blockers
MAT +5.6 / QTR +3.4

ACEI
MAT +5.24 / QTR +3.53

Diuretics
MAT +12.71 / QTR +5.78

In term of market we have a very good balance with all of our 7 countries representing

double digits and this is reflected in our local sales which represent a health situation for

Procoralan, because most the countries are

growing by more than 20% right now as you can QT-ST EVOL N-
see. 1/DIC 15
COUNTRIES AVERAGE
+12
COSTA RICA 300 +27
+55
SALVADOR 196 +22
+24
GUATEMALA 408 +28
+28
HONDURAS 345 +27

NICARAGUA 138

PANAMA 267

DOMINICAN REP 293

SCAC 1,947

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

Procoralan
 Cardiologists are the main target, with almost 4x more potential of prescriptions vs
others.
 Angina patients: Our principal competitor is ranexa, we have just 1 country where
Ranexa has right now more MS than Procoralan, (Nicaragua), they were increasing
rapidly its sale because of the launching but now they are losing dynamism
 An internal qualitative survey has shown that reducing symptoms is the most
important need for doctors treating patients with angina.
 In HF patients: Our prescriptions are driven by the prevention of hospitalization,
improvement of exercise capacity and then mortality reduction.
 Related to factors that hinder the prescription, the main reason for not prescribing
Procoralan are mainly, because they do not have specific patient profile in mind and
also they said that the other treatment are good enough.

Today we are working to get the inclusion of Procoralan in the heart failure protocols in the
differens countries, in hospital listing, but also in the creation of the heart failure units in the
cardiologists’ services, because it doesn’t exist in any of our countries.

The full implementation of the Optimize HF Program in our countries should be one of our
main objectives, the inclusion of Procoralan in the different protocols and hospital listing is
very important, and is one of our main objetive.
Is clearly evident that doctors in general do not perceive Procoralan’s additional benefits in
terms of efficacy in both, angina or HF, meaning great’s opportunities for us in terms of
convince them on Procoralan efficacy and its use not only after a long titration of the other
treatments.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

2. PRODUCT POSITIONING

2.1. Key figures

The local sales of Procoralan during last financial year achieved 19,907 units with a growth

of 16%. PROCORALAN

Réel Cum A-1 Cum Dif % A-1
Cum

SEP/2014 17,174 14,948 15.0%
SEP/2015 19,907 17,174 15.9%

Procoralan 5mg represents 63% and 7.5 mg 37% of this sale, which means that we are
very similar that the last year.

Procoralan Sales in Units

7.5 MG, 7,365,
37%, +10

5 MG, 12,542,
63%, +20

During this year, at the beginning we face the result of signify that pushing us down, but
rapidly react, explaining this results through our KOL and the sales force, also we had main
event of the year “Myth and Reality” with almost 100 doctor from Central America and
Dominican Republic, we clearly succeeded in catching more and more the attention of
cardiologists and we are now on a trend that improves the monthly sales as we show below
in the evolution of monthly local private sales to pharmacies at the end of September 2015.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

We also had a review the target of the Procoralan team, taking out many GPs and focus
mainly in the cardiologists.

REVISION OF THE TARGET
OF PROCORALAN TEAM

OPTIMIZE HF PROGRAM

QT ST

Moreover, we had the implementations of the “Optimize HF program” that help us to gain
new advocate and the inclusion of Procoralan in the Heart Failure protocols and in the
hospital listing

CAD Market
The Coronary therapy class, C01D, right now is decreasing by 3.1%, but mainly because of
Vastarel MR is losing dynamism (-8%) and represent 81% of this class, as you can see
below.

The C01D market is decreasing
 MAT -3.17 / QTR -4,69

Procoralan
MAT +16 / QTR +19

Ranexa
MAT +18 / QTR +5

Vastarel MR
MAT -8,1 / QTR -10,7

MAT ~ 09/2015

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

In Central America and Dominican Republic the symptomatic stable coronary artery
disease market where Procoralan is currently indicated includes therapeutic class as C1D,
C1E, C7A, and C8A.

IMS MAT OCT-15

Beta blockers, the class C07A is the main class among the symptomatic treatment and
even are still dynamic, that’s mean a great opportunity for Procoralan, especially when our
promotion is related to combine it with them.
Symptomatic treatment in CAD including long acting nitrates, CCB, coronary therapy and
Beta Blockers are used in both, symptomatic treatment and as secondary prevention.

CAD market by products in units

RANEXA, PROCORALAN, NEBILET ,
22,568, 3% 35,082, 5% 108,348, 14%

VASTAREL MR CONCOR ,
, 233,047, 31% 181,806, 24%

COREG, IMS MAT NOV-15
179,065,

23%

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

The dynamism of the Ca Antagonists and particularly beta blockers is very good for us
because in angina patients, most of our promotion is related to the use of Procoralan in
combination with BB. And in the same way new drugs as Procoralan and Ranexa are also
growing which mean that there are many angina patients uncontrolled with the standard
therapy.

Heart Failure market
In the heart failure market, beta blockers are still the class with the main participations,
follow by ACE inhibitors and diuretics.

The HF Market growth by
MAT 6.2 / QTR 3.1

Beta Blockers
MAT +5.6 / QTR +3.4

ACEI
MAT +5.24 / QTR +3.53

Diuretics
MAT +12.71 / QTR +5.78

IMS MAT 09/15 UNITS

In terms of growth, the total HF market is growing by 6,2 and the C03A class, the diuretics,
shows the greater dynamism among all the classes in units, follow by de beta blockers,
that’s mean we have more and more opportunity with Procoralan.

The growth of beta-blocker is a very good symptom because our promotion is in
combination with them and also the dynamism of diuretics mean that we are in the
precense still of many descompensated patients and this is another proof that we have a
very huge opportunity to keep growing.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

In central America our main market in C01D class is Costa Rica with 20%, follow by
Panama and El Salvador, but in our local sales, Guatemala and Honduras are our main
contributors.

COUNTRIES QT-ST AVERAGE EVOL N-1/DIC 15
COSTA RICA 300 +12
SALVADOR 196 +27
GUATEMALA 408 +55
HONDURAS 345 +22
NICARAGUA 138 +24
PANAMA 267 +28
DOMINICAN REP 293 +28

SCAC 1,947 +27

In term of market we have a very good balance with all of our 7 countries representing
double digits and this is reflected in our local sales which represent a health situation for
Procoralan, because most the countries are growing by more than 20% right now as you
can see above.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

2.2. Perceived product image

Angina:
The most important goal for our cardiologists in Central America in the treatment of angina
is the reduction in angina symptoms and ischemia and the cardiologists consider that
Procoralan achieve most of the mains reasons to prescribe an antianginal drugs as you
can see below.

An internal qualitative survey (3 countries) and 25 questionnaires have shown that reducing
symptoms is the most important need for doctors treating patients with angina.

What are your most important goals in treating angina

120%

100%

80%

60%

100% 100%

40%

60% 60% 60% 50%
20%

0%

Reduce Improve Reduce Increase Reduce Reduce

ischemia coronary angina exercise myocardial Mortality

perfusion capacity infarction

How Procoralan achieve these goals?

(0=no benefits, 10 very strong benefits)

10

9.5

9

8.5

8 9.3 9 9.1
8.5 8.7 8.5
7.5

7 R edu ce Increase R edu ce R edu ce
Reduce Improve angina exercise myocardial Mortality
ischemia coronary capacity inf arc tio n
perfusion

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

The efficacy in reducing myocardial infraction and increase exercise capacity in CAD
patients is also important for cardiologists. Some of the doctors prescribe mainly
Procoralan because of the reduction in heart rate, but have no clear a differentiating of
Procoralan versus the other antianginals.

Cardiologists perceive the classical antianginal drugs as beta blockers as very effective in
reducing angina. Doctors perceive Procoralan as inferior, in reducing angina, compared
with -blockers and at same level with the other antianginal drugs such as ranolazine.

In terms of prescription habits, it can be observed that Procoralan is mostly used after the
other antianginal agents.

Related to factors that hinder the prescription, the main reason for not prescribing
Procoralan are mainly, because they do not have specific patient profile in mind and also
they said that the other treatment are good enough.

Most of our patients are CAD patients who are intolerant to beta blockers or with a
contraindication or others that already have beta blockers and continue with symptoms.

Pooling trial data confirm the significant antianginal efficacy of Procoralan across different
subpopulations, including patients after myocardial infarction or revascularization, or
patients with diabetes as comorbidity.

Feedbacks from the field tell us that the cardiologists are mostly concerned with reducing
the number of attacks of angina and improving exercise capacity in CAD patients.
Related to CAD patients, doctors often told us that their patients are sufficiently “controlled”
especially after PCI of CABG with beta blockers alone.

Heart Failure
Today we are working to get the inclusion of Procoralan in the heart failure protocols in the
different countries, in hospital listing, but also in the creation of the heart failure units in the
cardiologists’ services, because it doesn’t exist in any of our countries.
In the same way we are sending cardiologist to Costa Rica, to the only private heart failure
clinic in Central America, the “Clinica Biblica”.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

The cardiologists stay there for around a week to learn in the best way how to treat and
follow the HF patients and after this experience they can initiated this kind of program in
their countries. We call this program “Rotation in the clinica Biblica” that is part of the
international OPTIMIZE Program. Below we have a summary of this program.

COUNTRIES PROTOCOLS HOSP. LISTING ROT. IN CL. BIBLICA CREATION OF HF UNITS

PANAMA ST. TOMAS HOSPITAL ST. TOMAS HOSP. DR. ALEXANDER ROMERO ST. TOMAS HOSPITAL
SOCIAL SECURITY IN PROCESS FRED MARTINEZ (NURSE) DR. BALDOMERO GONZALEZ
DR DOMINGO CORREA

COSTA RICA CLINICA BIBLICA IN PROCESS

DR. MARIO SPERANZA DR. CARLOS BRENES

HONDURAS SOCIAL SECURITY IN PROCESS DR. CARLOS RAMOS DR. GUSTAVO MONCADA
GUATEMALA PRIVATE CLINIC

SOCIAL SECURITY

DOMIN. DRA. OLGA CAMILO IN PROCESS
REP.

DRA. ANEYIS ALCANTARA

In terms of HF treatment the most important goal for our cardiologists in Central America is
the reduction of the HF symptoms and the mortality and the cardiologists consider that
Procoralan achieve these mains reasons to prescribe.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

The majority of our patients are patients with HF who do not tolerate higher dosage of
betablokers and they are still symptomatic.

Procoralan is still prescribed late in the patient pathway because our cardiologists do not
fully perceive the additional clinical benefits of Procoralan.

Procoralan is still prescribed after a long titration of the other treatments, but now with our
promotion in comorbidities or risk factors as diabetes, low blood pressure, renal dysfunction
or COPD, we have great opportunities to increase the prescription of Procoralan

In one sentence our doctors’ say that Procoralan represent a very important option for all
our patients with HF.

Feedbacks from the field tell us that the cardiologists look for reduce the symptoms and the
mortality, but also to improve cardiac function.

Right now Procoralan is included in Guatemala’s social security listing and also included in
the list of the ministry of health of Panama and in the local protocols in Honduras, Panama
and Costa Rica. We are working in the inclusion of Procoralan in the Panama’s social
security.

The full implementation of the Optimize HF Program in our countries should be one of our
main objectives, the inclusion of Procoralan in the different protocols and hospital listing is
very important, and is one of our main objetive.
Is clearly evident that doctors in general do not perceive Procoralan’s additional benefits in
terms of efficacy in both, angina or HF, meaning great’s opportunities for us in terms of
convince them on Procoralan efficacy and its use not only after a long titration of the other
treatments.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

2.3. Perception of competitor products

Heart Failure
In heart failure patient we have a new product in process to launch, Sacubitril / Valsartan
(24/26mg-49/51mg-97/103mg), Entresto ®, but Procoralan has demonstrated its benefits in
combination with a RAAS blocking agent as Entresto, and the mode of action between
Entresto and Procoralan are different and will have complementary benefits on HF death or
hospital readmission.
The initial good perceptions of Entresto can be used as an opportunity to reinforce the
clinical relevance of Procoralan for the heart failure patient.

Angina
In Angina, ranolazine is our main competitor in our region and they are promoting its
benefits, especially its reduction in angina attacks, nitrates consumption and benefits on
exercise capacity, but they do not have any results in prognosis.

Its promotion is facing directly Procoralan and their key message are focused on the
benefits in terms of symptoms, whatever the comorbidities and with no effect on heart rate
or blood pressure.

The communication of Ranexa is mainly supported by the CARISA study (823 angina
patients), which assessed ranolazine’s effect on top of standard doses of atenolol,
amlodipine, or diltiazem. At 12 weeks, Ranexa 750 mg twice daily reduces angina attacks
by 24% and nitrate consumption by 32%, and improves ETT parameters. Unlike Procoralan
(BEAUTIFUL angina), Ranexa did not improve prognosis in the MERLIN-TIMI study (6500
patients). Ranexa has no effect on the risk of CV death or MI in patients with prior angina.

The cardiologists are using ranexa in Angina patients with HR < 70bpm, they also say that
has a very high price and some of them say that they use it in combination with Procoralan

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

IMS MAT NOV-15 UNITS

COUNTRIES PROCORALAN RANEXA

COSTA RICA 6,230 3,073

SALVADOR 4,259 2,623

GUATEMALA 7,840 4,156

HONDURAS 7,961 5,349

NICARAGUA 2,869 4,920

PANAMA 5,922 2,447

DOMINICAN REP 3,888 0

TOTAL 35,082 22,568

We have 1 country where Ranexa has right now more units sold than Procoralan, is

Nicaragua, our smaller market.

In the Benchmark in units, we can see here that ranexa during its launch time increase

rapidly, but now they have less dynamism than Procoralan

In turnover, because it’s high price, ranexa has more MS that Procoralan.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

Ranolazine´s promotion is facing directly Procoralan. Its promotion is related to the benefits
especially in the reduction in angina attacks, nitrates consumption and benefits on exercise
capacity. In this moment they have just 1 country (Nicaragua) with better sales than
Procoralan. During its launch time increase rapidly, but now they are losing dynamism.

2.4. Feedback on product promotion

In heart failure management our prescriptions are driven by the prevention of
hospitalization, improvement of exercise capacity and then mortality reduction, mostly in
private clinical practice instead of hospital practice and that’s why we have just 23% of our
prescription in HF, because most of the HF patients are in the hospital.

The improvement of prognosis is not fully perceived by doctors, we need to insist in this
benefit provided just by Procoralan, reducing MI and CV death.

The tolerability is very well accepted by doctors, so that is another reason to gain
prescription when they compared Procoralan against beta blocker.

In our current campaign we are focusing in how Procoralan double the gain in the effort
capacity and the reduction in the hospitalizations as you can see below and most of the
cardiologists are interested to try with Procoralan in heart failure patients, but they said that
is not easy to find the right patient profile.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

In angina, we focusing in the powerful reduction on angina attack and the superior efficacy
against ranolazine, even in patients after PCI, as you can see below
In angina management, some cardiologists reported that few of their Angina patients are
eligible for Procoralan since in the era of revascularization they nowadays have fewer
angina patients.

We are reinforcing the benefits on Angina patients reducing myocardial Infraction and
doing the link between angina and HF patients.

Nowadays we know that most of our prescriptions coming from patients who do not tolerate
or have contraindications with beta blockers; this means mostly patients with COPD or
patients with normal or low blood pressure.

2.5. Key environment-related facts

Guidelines
The last year for the first time in Central America and the Caribbean we had the first
consensus for the diagnosis and management of heart failure, which represent the first
step in the development of the Guidelines for HF.
Right now we don’t have guidelines and most of the countries follow the American ones or
the European guidelines.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

Epidemiological data
The heart failure mortality is not well determined in the countries in Central American. To
have a perspective, Internacionales1,2 studies in the United States of America tell us that
they have 650,000 new cases each year, this condition are worsening by age, being 20 per
1,000 people between 65 and 69 years, to more than 80 per 1,000 people after 80 years,
with a prevalence of 0.4 to 2% in the general population. In Europe an estimated
prevalence of 1 to 2% in the general population and more than 10% in those over 70 years
is estimated. The prevalence of heart failure in our region is estimated at 2,% of the
population, regarding ischemic heart disease percentage is estimated much higher in about
8% of the adult population.

1- Véronique L. Roger. Epidemiology of Heart Failure; Circ Res. 2013;113:646-659.
2- Braunwald E. Shattuck; Lecture–cardiovascular medicine at the turn of the millennium: triumphs, concerns, and

opportunities. N Engl J Med. 1997;337:1360–1369.

In Central America, 31% of all deaths were attributable to cardiovascular diseases.
Predictions for the next two decades include a near tripling of ischemic heart disease and
stroke mortality in Central America.

Hypertension is one of the most important risk factors for heart disease and affects
between 8% and 30% of the region’s populations and coronary artery disease is the first
cause of death in our countries (Ministry of Health, Social Security Fund, OPS, San Jose
Costa Rica 2005). We have a population of nearly 54 million that mean an important
market to help us to grow

The nutrition in our Region is characterized by a low consumption of fruits, vegetables,
whole grains, cereals, and legumes. This is coupled with a relatively high consumption of
foods rich in saturated fat, sugars and salt, among them milk, meats, refined cereals, and
processed foods. This dietary pattern is a key factor leading to a rise in prevalent
overweight and obesity. Population–based surveys from Central America show that, in
2002, 50% to 60% of adults and 7% to 12% of children less than 5 years of age were
overweight or obese.

World Health Organization. WHO Global Report. Preventing Chronic Diseases. A Vital Investment.Geneva:
WHO; 2005.
Yach D, Hawkes C, Gould CL, Hofman KJ. The Global Burden of Chronic Diseases. JAMA 2004;291(21):
2616–2622.

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OPTIMIZE International HF Program
Our members of the Optimize International HF program are Dr. Mario Speranza, Dr.
Baldomero Gonzalez and Dr. Gustavo Moncada.

OPTIMIZE HF PROGRAM

Name Country

Dr. Baldomero González Panama

Dr. Mario Speranza Costa Rica

Dr. Gustavo Moncada Honduras

Targeting

KOL Mapping

Also among all the doctors, we have our Pyramid based on the Servier potential and their

prescription and influence as we can see below.

Daniel Pichel Panama Juan Carlos Elizondo C Rica Mario Speranza C Rica

Julio Guillén Guatemala Omar Alonzo Guatemala

Alexander Adames Panama Baldomero Gonzalez Pan

Gustavo Moncada Hond

Alfaro Marchena Pan

Gerardo Sosa Hond

Potential Servier Rafael Díaz Panama Pura Henríquez Rep Dom Jose Aguirre Panama
Rubén Nieto Panama
Armando Garrido Pan Guillermo Perez Nicaragua Dario Vera Rep Dom

Carlos Revelo Castro Salvad. Jonathan Poveda C Rica

Daniel Meneses Nicaragua Thelma Sanchez C Rica

Hugo Villarroel Salvador

Frank Valdez Rep Dom

Pablo Hurtado Nicaragua

Prescription + influence

Procoralan Prescriptions

According to the IMS data (june-16) our main prescribers are Cardiologists, GPs and

Internal medicine. Procoralan Prescriptions

NEUROLOGIA,
520, 5%

MEDICINA MEDICINA
INTERNA, 1,727, GENERAL, 3,259,

17% 32%

CARDIOLOGIA,
4,675, 46%

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

PROCORALAN 10,181 Total Pot-Total

GPs 3,259 31,757 0.1

CARDIOLOGISTS 4,675 967 4.8

INTERNAL MEDICINE 1,727 2,701 0.6

In terms of potential, the cardiologists have a big different with other specialities, as you
can see above and that’s why we are focussig in this group of doctors.

The Procoralan prescriptions coming mainly by Angina and Ischemia in 53%, follow by
heart failure by 16%. And if divide our prescription in our two indication, we have 77 in
angina and ischemia.

Procoralan's Prescriptions

HF,
1,629,
23%

Angina
Ischemia,
5,396, 77%

According to data from IMS, cardiologists should be our main target because they can give
us more prescriptions of Procoralan than other specialist as Internal medicine or GPs

2.6. Expected key items related to the product

The upcoming inclusion of Procoralan in different protocols and hospital listing represent a
great opportunity for us, especially because most of the heart failure patients are in the
hospital.

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2.7. SWOT analysis

2.7.1 Strengths/Weaknesses - related to the product WEAKNESSES
STRENGTHS

Perceived by the doctor Perceived by the doctor
 Recommended in International  Lack of clear visualization on patient
guidelines profile
 Clinical benefits ; mortality and  Fear of bradycardia,
hospitalization for HF patients  Late prescription (due to the
 Better tolerability than BB uptitration of the other treatment)
 Effective in reducing Heart rate  Recommended as second line in
 Inclusion on Guatemala social angina
security listing  No improvement in prognosis in
angina patients

Not perceived by the doctor Not perceived by the doctor
 Effective in relieving angina
 Improvement in exercise capacity 
 Improving the prognosis (MI) in 
angina patients with LVD 
 Most tested anti-anginal
 The added benefits in combinations
with BB in both Angina and HF
 Short term improvement in cardiac
function

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2.7.2 Opportunities/ Constraints -Threats - related to the environment

OPPORTUNITIES CONSTRAINTS-THREATS

 Increasing recognition that  Direct targeting by Ranexa in most of
revascularization doesn’t resolve all the countries.

 Unmet needs for post-MI,  Non availability of Procoralan in some
revascularized, and diabetic coronary hospitals’ protocol
patients
 Doctors are satisfied with first line
 Increasing number of patients with
Angina and heart failure

 Need to optimize in hospital
before/after discharge

 Experiences in US market
 Optimize HF / protocols needs

2.7.3 Diagnosis

Doctors do not have a clear clinical situation to prescribe and do not perceived the need to
add Procoralan in both Angina and HF and they continue to use it too late and in a limited
clinical situations as in severe patients or with contraindication to beta blockers.

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3. ORIENTATION

3.1. Strategic goal

To illustrate specific clinical situations in which Procoralan added now on top of beta-
blocker in HF and Angina patients provides greater clinical benefits

As

Angina relief, improvement in exercise capacity and rapidly improves systolic function,
keeping HF patients stable.

3.2. Promotional axis and main messages

By adding Procoralan now, on top of beta-blockers
Angina
For you patients with self-limiting in daily activities* Procoralan provides more angina relief,
improvement in exercise capacity.
HF
For hospitalized patients*, you rapidly improve the systolic function, keeping them stable
with fewer symptoms, fewer hospitalization and better survival.

Clinical situations to be adapted*

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3.3. Operational strategy (main strategic orientations in term

of media mix)

 Detailing Scheme / Visual Aid and leaflet
o HF

Procoralan rapidly improve systolic function, keeping the HF patient stable. It means
that with Procoralan you offer greater clinical benefits:

 have less breathlessness, can do more daily activities
 Patients spends fewer days inside the hospital,

 Patients live longer (-39% reduction in HF deaths).

Procoralan is effective, safe, and easy to use in a broad range of heart failure patients,
even in patients with associated conditions, for instance with renal dysfunction, diabetes,
COPD, and low blood pressure.

o Angina
Procoralan improves myocardial perfusion, increasing the diastolic filling time, coronary
reserve and coronary collateral circulation.

Procoralan provides greater clinical benefits, offering:
 more relief from angina attacks
 more daily activities through more exercise capacity

Procoralan effective, save, and easy to use in a wide range of angina patients, even in
post-revascularization, post-MI, diabetes, with self-limitation in daily activities o elderly.

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4. APPENDIX

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O PRIENTATION LAN 2016 / 2017

Country: Central America

Product: COVERAM

PROJECT MANAGER: Natalia Díez-Hochleitner Cousteau

TO 604000 usd Evolution (%)
Unit 23793 15%
16%
Contribution to 2.6%
subsidiary TO

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Contents

1. SUMMARY ..................................................................................................................... 14
2. PRODUCT POSITIONING ............................................................................................. 16

2.1. Key figures ............................................................................................................. 16
2.2. Perceived product image ...................................................................................... 22
2.3. Perception of competitor products ...................................................................... 23
2.4. Feedback on product promotion .......................................................................... 24
2.5. Key environment-related facts.............................................................................. 26
2.6. Expected key items related to the product .......................................................... 27
2.7. SWOT analysis ....................................................................................................... 28

2.7.1 Strengths/Weaknesses - related to the product ............................................ 28
2.7.2 Opportunities/ Constraints -Threats - related to the environment............... 29
2.7.3 Diagnosis .......................................................................................................... 29
3. ORIENTATION............................................................................................................... 30
3.1. Strategic goal ......................................................................................................... 30
3.2. Promotional axis and main messages ................................................................. 30
3.3. Operational strategy (main strategic orientations in term of mediamix) .......... 31
4. APPENDIX ..................................................................................................................... 32

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1. SUMMARY

Hypertension is one of the most common diseases in the world, also very dangerous
since most of the time it remains asymptomatic. In our region, half of the adult population
11.2 millions are hypertensive and not all of them are aware of it, only half of them are
treated (5.1 millions), and from the treated patients 30% are uncontrolled (OMS). It
remains a huge problem to solve for this hypertensive patients that are suffering and
could have a better and longer life. We have a big opportunity of growth with Coveram.

 Total Hypertension Market ACEi + ARBs (mono and combo):
At September 2015, the total market of hypertension ACEIs and ARBs represents:
- 5 597 212 units. Growth: +6.34%
- 105,618,403$. Growth: +5.43%

 COVERAM sales:
According to IMS, from September 2014 until September 2015, market share of 0.3%.
- 19 799 units. Growth: +13.85%
- 710 408 $. Growth: +19.05%

Our direct competitors in the whole market are decreasing their sales compared with

last year, but combinations with Olmesartan are gaining prescriptions focused on a family

strategy to a huge target of Doctors.

MAT ~ 09/2015 MAT ~ 09/2015

UN-T.UNITS UN-T.UNITS

COAPROVEL S.A 320593.00 -2.79

EXFORGE NVR 264955.00 -11.63

CO-DIOVAN NVR 259305.00 -11.33

EXFORGE HCT NVR 196358.00 -3.98

BENICAR AMLO MEN 174498.00 17.36

BENICAR HCT MEN 149628.00 5.69

COVERAM SVR 19799.00 13.85

The main factor that induces prescriptions is the experience and the confidence of the
doctors in the products, we have being working on this issue around “trying the product”
to have the experience and really get the results of a superior efficacy against ARB.

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Those, who have already tried Coveram, mainly prescribe 5/5 for the first time, but as we
were focusing also our message in sever patients or patients with comorbities doctors,
also prescribe the dosage of 10/10.

For the moment Coveram is not enough differentiated from the combinations with ARBs,
since perindopril was not well established in the region, Doctors are afraid from the
cough and think that it is a treatment not “on vogue” now. We also face the fact that
doctor’s don´t have enough experience with Coveram and are in a comfort zone with
their ARB treatment, it is not easy to change their way of treatment if they do not try
and believe in the product.

Considering that the monotherapies still represent 51% of the market and still growing,
we should consider to enlarge the benefits of Perindopril, to highlight the superiority of
COVERAM versus the other Amlodipine combinations to capture patients uncontrolled
by monotherapy with ARBs also, not only uncontrolled by ACEi which are already
most of the Coveram patients that we have.

 Our main objectives will be:
1. Develop an hypertensive family strategy with all our products and build the

success of Coveram based also on Coversyl and helping the launch of Triplixam.

2. Maintain our message as simple as possible focused on efficacy always being
superior to ARB combinations.

3. Increase our share of voice and become a bigger actor in the market, targeting
also more GPs taking advantage of the experience of the specialists.

4. Raise Champions in our region and regional speakers of perindopril and our
hypertensive market with the confidence and the experience to influence others
and enlarge the use of Coveram in our region differentiating us clearly from ARB

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2. PRODUCT POSITIONING

2.1. Key figures

▲Hypertension Market: ACEi + ARBs ▲COVERAM Market:
- 5 597 212 units. Growth: +6.34% -19 799 units. Growth: +13.85%
- 105 618 403$. Growth: +5.43% - 710 408 $. Growth: +19.05%

Our market is clearly driven by ARBs with a market share of 82% of the market, where
monotherapy has the biggest growth in terms of $ showing that for the treatment of an
hypertensive patient, monotherapies still remains one of the choices of the Doctors,
followed by combinations. We have to increase our share of voice, since we are one of
the only ACEi to be promoted in our region, ACEi are not as good perceived as ARB.

-7%

+5%

+4%

+11%
ARB = 82% of Market

We are still a small actor on one of the biggest market, but with the highest
opportunities to grow as hypertension still remains one of the first causes of death in the
world that remains asymptomatic. And in our region in the top 10 of the most prescribed
drugs are our direct competitors and we can also be in that place.

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In terms of dynamism we are on the way to grow each time more, and in the last months is
getting much better as we can see with our QTR results with a growth of +44% for
COVERAM the most dynamic hypertensive drug in combination, but our competitors
did a very good job in terms of share of voice and number of contacts.

+44

BENCHMARKS
If we analyze their strategies, they are totally different as the Olmesartan family grows all
together beginning by their monotherapy and the Valsartán family on the contrary each
time they have a new launch they get focused on their new product losing the dynamis
of the whole family based on Valsartan benefits.

29%
33%
38%

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22%
18%
30%
3022%%
%22%
%

In our situation with the Perindopril family we nowadays have, expecting the launch of
Triplixam in the next months, Coversyl is at the heart of our family, we are building our
strategy taking in count the advantages of Coversyl as Menarini does with Olmesartan.

30%
29%

41%

LOCAL SALES:

Our local sales in October 2015 have a growth of 69% in Units, driven directly as follows:

Réel Cum A-1 Cum Dif % A-1 Cum

COVERAM 10/10 MG 629 316 99%
COVERAM 10/5 MG
COVERAM 5/10 MG 479 349 37%
COVERAM 5/5 MG
223 81 175%

1394 867 61%

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Our “best seller” still remains 5/5 combination, but we also promote a lot the 10/10 in
our promotional message since our superior power in reducing blood pressure in severe
hypertensive patients, with a growth of 99%. It is also very good news that the
combination of 5/10 grows 175% as most of doctors were afraid of the edema.
Coveram in local sales is growing in the region in Units, with differences in the countries,
the biggest market is Panamá (+46%), followed by Honduras (+8%) and Guatemala
(+302%).

 Talking about two examples with the biggest growth in cumul October 2015:
Guatemala: +302%
Dominican Republic: +157%

2.2. Perceived product image

We did a qualitative survey involving the whole region, asking about Coveram main facts, in
terms of patient profile and benefits to 49 Doctors.

 Reservoir of patients: Most of them are previously treated with an ACEi and
severe HT

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 Reasons to prescribe an hypertensive drug:
The main reason for a doctor to prescribe is the efficacy that is why we focus now a
simple and strong message on efficacy to make them see the superior efficacy of Coveram
compared with ARBs. But we have to make more noise on the central BP efficacy.

 Reasons to prescribe Coveram
The main advantages of Coveram are: “Efficacy”, “better quality of BP control”, and “a
better evidence of CV protection”. Efficacy is where we focus our promotion, so we are
on the good way to show Coveram´s biggest advantages, but competitors also
promote the same benefits with a much higher share of voice, we have to be different
and prove it to our Doctors and make them change.

 KEY FACTS: Coveram perceived as a drug

Doctors reason to prescribe an HT drug 1. Powerfull efficacy
2. Better Quality of BP control
1. Efficacy 3. Better evidence CV protection
2. Central BP efficacy
3. Tolerability
4. Target organ protection

Comparing what Doctors needs and what Coveram gives them, we realize that little by
little they are perceiving Coveram as powerfull but we have to talk more about Central BP
efficacy to be different and superior to ARBs. And on the other hand they have issues
and are afraid of tolerability; we should reinforce it to let them convinced and confident
with the side effects.

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2.3. Perception of competitor products

Our main competitors : fixed combinations Sartans/Amlodipine and Sartans/HCTZ, the
Valsartan and the Olmesartan family are used by our Doctors due to several factors as:

 “ en vogue” products with aggressive promotion:
They focus their promotion on a simple and strong message, they repeat all the yearlong.
The have a team 10 times bigger than we do, with revisit calls. On the one hand Menarini
focus his promotion mostly on GPs maintaining a good relationship with the most
important specialist giving them special attentions and congresses. Novartis focus his
target on specialists and GPs . In terms of message: EXFORGE HTC and EXFORGE are
focused on the strong efficacy and all the other products as DIOVAN and CODIOVAN, so
does Menarini also talk about his Hypertension franchise focusing on the efficacy and
also the good tolerability.

 Low share of voice and awareness of perindopril and ACEi:
We are the only pharmaceutical company promoting an ACEi in combination. All other
ACEIs are generics and commonly used in the social security of our region, where Doctors
have being told that all ACEi have a high rate of cough. Coversyl awareness and share
of voice is not well implemented. So, in terms of awareness, it’s more difficult for us to
compete against sartans, since we have to build the path again, beginning with Coversyl
and going to Coveram, to prepare also the new launches of the perindopril family. Doctors
are used to prescribe Sartans and do not want to change their patients from their
treatment, since they think they are good treated.

2.4. Feedback on product promotion

The Doctors accept very well a simple message focusing on the strong efficacy of
Coveram, and repeting it as much as possible, not changing our message allows them
not to forget it and to begin to try it in more and more hypertensive patients. Doctor´s
mostly use Coveram in severe patients or with comorbidities, but do not see Coveram
superior as other treatments as ARBs.

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They still do not see the difference of switching to Coveram and so far have not
discovered the benefits that no other combination can give them.

 KEY POINTS WHERE WE SHOULD ACT:

1. Powerful blood pressure: Doctor´s can get the results very fast and the patient
measures it. Doctors are impressed with the -63 reduction with 5/5 Coveram, but
they do not perceive it as superior as the ARBs combinations.

2. In terms of control, Doctors don´t perceived the difference using Coveram, a 24
control is crutial to protect the key organs but also regarding the quality of this
control. Where perindopril is different from other RAASi, having one of the highest
trough to peak ratio.

3. Giving the doctors more samples to try and initiate more patients with Coveram,
this will give them the confidence to enlarge the treatment to more patients; this is
one of the strategies in Hypertension of our competitors.

2.5. Key environment-related facts

 Guidelines:
New Lash Guidelines from March 2015, in Latin America, guidelines are available for the
management of hypertension at three levels: national, regional and international. The
national and regional Latin American and Caribbean (LAC) guidelines are in fact
adaptations of the international guidelines. The potential benefit of applying guidelines
developed in other regions to local healthcare decision making is that it will enable decision
makers to take advantage of existing analyses and transfer or adapt them to their local
contexts.
In Central America, since JNC7 recommendations and the different versions of American
Guidelines of this past year most of the Doctors prefer the European guidelines, which
are simpler and practical for everyday practice, based on the cardiovascular risk of the
patient despite the historic American influence of the region. Now after SPRINT Trial
Doctors are waiting for the new guidelines to come out.

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Orientation Plan 2016/2017 Country: Central America and the Caribbean
 Epidemiological data:

If we specify per country those data, we can settle down that the 3 main countries with the
highest prevalence are in order of importance: Guatemala, Panamá and Dominican
Republic. Guatemala is the biggest country of our region with more than 15 Million
people, but now with many politic constraint that affects directly all the markets in terms
of commerce. Panamá is our biggest market in hypertension with also the highest
economic level of the region, so it is a priority to focus our business in Panamá.

TARGETING:

 INTE IMS:
In the hypertension market of RAASi in combination most of the prescriptions comes from
the GPs (71%-61%), as in our region GPs are the first ones to treat the patients and to
maintain their treatment, always taking in count the specialist point of view, we have a big
opportunity with them making awareness with some selected GPs.

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If we take in count the global results from some of our competitors and the market,
the highest percentage of prescriptions comes from the GPs, where we nowadays
are not so strong.

 EASYMED:
This is our target visited Doctors in the region, 66% are Specialist, and 34% GPs.

2.6. Expected key items related to the product

 Launch of Triplixam in February 2016 in our region and the Launch of Prestalia in
2017.

 Publication of the new LASH Guidelines
 SPRINT Study: may induce changes in the way of treat Hypertension
 Launch of triple combination of Menarini and other competitors

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2.7. SWOT analysis

2.7.1 Strengths/Weaknesses - related to the product WEAKNESSES
STRENGTHS

Perceived by the doctor Perceived by the doctor
 Product of quality  Not yet seen as superior to
 Strong evidence ARB/amlodipine combinations
 Cardiovascular benefits  Not enough regular users of
COVERAM (only 4%)
 Small Sales Team

Not perceived by the doctor Not perceived by the doctor
 More powerful then ARBs in efficacy  Lack of confidence with COVERSYL
 Unique mortality data & COVERAM
 Excellent tolerability profile  Lack of speakers for COVERAM
 Lack of experience

2.7.2 Opportunities/ Constraints -Threats - related to the environment

OPPORTUNITIES CONSTRAINTS-THREATS

 Huge reservoir of HT patients  Perindopril’s benefits not well
uncontrolled established

 Competitors still do not have any  Aggressive promotions from ARBs
mortality reduction studies  Not included in any health insurance

 Registration in Costa Rica

2.7.3 Diagnosis
Doctors need to:

 Be confident with Coversyl and believe in its efficacy to understand why to use
Coveram

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 Try Coveram and have the experience of the efficacy in their patients
 Use it for everyday hypertensive patient, mild to moderate not controlled on ARBs

in monotherapy or in combination.

We need them to switch and try COVERAM as soon as possible, establishing first the
efficacy and the safety of Coversyl to let them confident to try the superior efficacy of
COVERAM compared to ARBs, in terms of Central Blood pressure and 24 hour control
with unique lifesaving benefits in each of their hypertensive patient not controlled on
ARBs in monotherapy or in combination

3. ORIENTATION

3.1. Strategic goal

Doctors have to switch their patients from an ARB in combination to Coveram since its
efficacy is superior in terms of BP reduction and in the quality of the 24 hour control
protecting their patients with unique lifesaving benefits. To ensure and be confident
through their experience of COVERAM’s superior efficacy, they first need to believe in
Coversyl and perindopril differences from the ARBS to understand why switching and
trying Coveram.

How are you going to say it?

Thanks to Coversyl and its benefits, switch your hypertensive patient treated
with an ARB in combination to Coveram, try the strongest treatment in
combination with Amlodipine, making your own experience and fulfilling your
needs since:

1. More powerful than ARBs in combination
2. Quality of the 24 control
3. Unique lifesaving benefits

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3.2. Promotional axis and main messages

“the more you try, the more you trust on the highest efficacy of COVERAM”
 Coversyl benefits, at the heart of Coveram
 Strong efficacy, superior to any ARB combination
 Switch to Coveram and try its benefits to be confident
 Patients treated with ARB in monotherapy or in combination
 Safe drug with an excellent tolerability profile

3.3. Operational strategy (main strategic orientations in
term of mediamix)

 Detailing squeme with Coversyl at the heart of the call to gain prescriptions and
awareness of perindopril in all our perindopril family

 More samples to the doctors
 Wide target: increasing the number of GPs, selecting them taking in count their

potential and number of patients
 Educational programs with GPs around 24 hour control with MAPA
 Building a family strategy with a brand name for all the family and vademecum

4. APPENDIX

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O PRIENTATION LAN 2016 / 2017

Country: Central America and the
Caribbean

Product: NATRIXAM

PROJECT MANAGER: Giovanni COLUCCI

Evolution (%)

TO
Unit

Contribution to
subsidiary TO

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Contents

1. SUMMARY ..................................................................................................................... 14
2. PRODUCT POSITIONING ............................................................................................. 16

2.1. Key figures ............................................................................................................. 16
2.2. Perceived product image ...................................................................................... 22
2.3. Perception of competitor products ...................................................................... 23
2.4. Feedback on product promotion .......................................................................... 24
2.5. Key environment-related facts.............................................................................. 26
2.6. Expected key items related to the product.......................................................... 27
2.7. SWOT analysis ....................................................................................................... 28

2.7.1 Strengths/Weaknesses - related to the product ............................................ 28
2.7.2 Opportunities/ Constraints -Threats - related to the environment............... 29
2.7.3 Diagnosis .......................................................................................................... 29
3. ORIENTATION............................................................................................................... 30
3.1. Strategic goal ......................................................................................................... 30
3.2. Promotional axis and main messages ................................................................. 30
3.3. Operational strategy (main strategic orientations in term of mediamix) .......... 31
4. APPENDIX ..................................................................................................................... 32

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1. SUMMARY

We just launch Natrixam at the end of our last financial year and we achieved 8,364 USD
and 494 units. We have not local sales during our last financial year.

Natrixam 1.5/5mg NATRIXAM
Natrixam 1.5/10mg 400 81%

Total 94 9%
494 100%

During our three first months of our local sales, we have sales of 4 of our 7 countries for
reason related to the registries.

Hypertension market is growing and mainly by the combinations, this represents a very
good opportunity for Natrixam in this huge market where diuretics and CCB are highly used

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Orientation Plan 2016/2017 Country: Central America and the Caribbean

2. PRODUCT POSITIONING

2.1. Key figures

We just launch Natrixam at the end of our last financial year and we achieved 8,364 USD
and 494 units. We have not local sales during our last financial year.

Natrixam 1.5/5mg NATRIXAM
Natrixam 1.5/10mg 400 81%

Total 94 9%
494 100%

During our three first months of our local sales, we have sales of 4 of our 7 countries for
reason related to the registries.

Hypertension Market
In the hypertension market almost all the classes are growing, which is a very good sign,
because of the number of hypertensive patients, knowing than most of them are still
uncontrolled and even more because the diuretics are the most dynamic class with a
growth of +11. Natrilix SR is the first diuretic in central america.
Another important point is that the combiantions have already more than 50% of te
hypertension market, wich represent a very good opportunity for Natrixam as you can see
bel

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In term of products, the main participation coming from BRA II in combination with
Coaprovel, Exforge and Codiovan, but Norvasc and Natrilix SR have also a good
participation which represents good news for us.

The contributions by countries of our first sales coming mainly by Guatemala and
Honduras.

Hypertension market is growing and mainly by the combinations, this represents a very
good opportunity for Natrixam in this huge market where diuretics and CCB are highly
used.

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