Sanofi SA (SNY) 2003 Q4 法說會逐字稿

Once again, a very good year. And let me stress this and we shall seek to do this rapidly and clearly, to point out that the true success of 2003 is once again acceleration in the growth of our business. Consolidated sales plus 15.6 on a comparable basis, one of the best performances in the industry that our sales figures are between the 15.6 and 20.4 of developed sales, if we add the code promotion of BMS with the U.S. And this level of growth between 15 and 20% is quite outstanding, outstanding in the industry and this accounts for the results which stem totally from this growth.

Now, what's interesting - it's interesting because this is - has been part and parcel of the company's strategy for years now and it's part of our ongoing future strategy in our present plans. This growth is across all regions throughout some markets with high growth easier than others. Where we rush in, we cover those. But our determination is to have strong growth across regions. Europe - 10.4% - that's above the market, of course. The U.S., where we are beginning to achieve high volumes with a growth rate of 33%. This is consolidated even higher over 40% in developed sales. Without doubt, it's the finest performance in the sector. Hanspeter will show you the numbers later and this famous rest of the world, which is crucially important because it is carrying the future development in the future years. In this rest of the world, we do have performance significantly above the market.

All markets, but also all products, another major characteristic of this company and I believe I have said this on several occasions. Of course, the top 10 products achieve 20% growth rate, which is important, representing now 67% of our sales as against 61% last year. So there is, indeed, a concentration on these strong products. Or rather, these top products are growing so fast that they are gaining in prominence. But what is absolutely fundamental and very different for many of our competitors is this ability, this capacity to strongly support the rest of the portfolio that is - plus 2%, of course, Ticlid that is replaced by Plavix and the small Corotrof (ph). We have a mature portfolio, which is a stable, positive portfolio and this accounts for these results. No small countries. No small products.

The year has been fine in terms of activity. Also, fine on the R&D front. We won't rehearse all the 2003 results, but you know, that these have been very positive results for the strategic products - Aprovel, Plavix, indications, Eloxatine, huge success, Arixtra, certification including their Xactrol, registered in the U.S. The portfolio, on the early stage products, very favorable evolution there. The list of our products, moving from pre-clinical Phase 2A, heading to 2B, excellent year 2003 and, without doubt, in this early 2004, five Phase 3 studies. Jamar (ph) will give you more details about that in a moment. But this is a very fine piece of news, since it's only 2004. Very productive R&Ds capability, very productive when we look at the research volume and the results. Very productive R&D. A basis for sustainable growth.

EPS - now, EPS 21.5% in 2003, 21.5 - 21.9 if we fix including exceptional items for a few of those. Twenty-one point five, excluding exceptionals. This is 21.5 achieved without lowering R&D. In fact, my sourcing would note R&D with no - the capital gains on the sales of products, which is, of course, one way of achieving profit, but isn't the best way for future growth. This is a pure result, 21.5% growth in 2003, better than forecast. Let me remind you that at the beginning of the year, we said 20% on a one-for-one dollar basis. In September, we said 21.10 and we're ending with $1.01. For 113, we have the 20%. It's not 20, but it's 21.5, so we have every reason to be very pleased with this EPS growth. This is a trend. If we look over five years, you see that the five-year trend achieves 36.4% per year - a very fine performance.

This is - confirms what I was saying. We're not saying that there's a negative - of course, it's the negative, very unfavorable currency effect. We're not - there are no capital gains on disposals. You see that 2002, had we had the 2002 rate, the growth would have been, once again, 35.5%. But it is 21.4 and that is fine in itself. A very good year - a very good year in 2003. Strong growth because without strong growth of activities, it becomes far more difficult to sustain strong growth in result base. Healthiest growth comes from business growth. And this sustainable, strong growth is built on the research and the fine results of - accentuates the trend and profitable because without profitable growth, things are more difficult to sell. So a very good year in 2003, very good paper by (inaudible). Hanspeter?

Ladies and gentlemen, good morning. The year 2003 was the fourth consecutive year of double-digit growth for our company. All these years' growth was above the pharmaceutical industry, with a strong acceleration as of 2001. Outperforming not just the regional, but the worldwide market that is in the U.S. and Europe and the rest of the world. In the U.S., our performance is top of the top 20 in the industry.

In our home market, Europe, the top 10 - we were the best in 2003 - best performance levels. Since the foundation of Sanofi-Synthelabo, our European sales have grown year on year, a total - one billion between 2000 and 2003. This is tripled by our flagship, our strategic key products, but - as I will show you in a few moments. We are particularly proud of our performance in the U.S. We have been able to achieve a presence of close on $4 billion and there's from almost a zero base. This growth was supported by structures that were adapted to our opportunities. And after a strong growth of our structures in the U.S. in 2001 and 2002, we have devoted 2003 to quality aspects, crowned with success here. A recent study that shows the quality impact of the networks on the attitude of the specifiers in the U.S. and we're very well placed there.

In Japan, we are committed to repeating the U.S. business model. Having considerably reinforced our local development products, we're focused on our joint venture with Fujisawa and Daichi, the first to place nicely Ambien, the first level of class. And this only two years following launch. Recently, we acquired Ancoran (ph) rights from the Daicho (ph) partner and since the first of February 2004, we have our own sales force, as announced previously, a direct sales presence. From Ancoran, this sales forces will be extended on the basis of new compounds, including Plavix, that will be soon filed with the Japanese authorities.

Since 2000, our strategic products worldwide, have doubled their sales. Apart from Plavix and Ambien, Aprovel and Eloxatine complete this portfolio blockbusters with the potential to double, once again, through 2006, supplemented, at that time by Xatral. In 2003, the four existing products give us a very attractive position. In the blockbuster portfolio, you can see that only three companies have more blockbusters than we, in that portfolio. But it's true, in terms of growth, because our portfolio or blockbusters has, far and away, the greatest growth rate of all these portfolios, that is considerable hope for sustained growth.

Our product policy is not limited on these strategic - key strategic products, but other products, which are adapted to local markets, important for patients and also important for our income statement. Jean -Francois Dehecq stated our motto - no small products. No small markets. We are building the future, securing the future with our flagship products. Example here shown in Europe. But at the same time, keeping these very stable traditional products in 2003, even with a low growth of about 2%. Amongst our activities to ensure the sustained growth, life cycle management is of key importance. Successes such as that have been Eloxatine, which has overtaken (inaudible) in Europe, but also in the U.S. in all its indications are the results of this. Consequently, these measures that currently include over 100,000 patients in Phase 3 studies controlled, will not just be maintained, but accelerated in order to leverage to the maximum the potential of this product.

Now, for four years, our track record is unique in the pharmaceutical industry. It is the result of a very efficient and sustained organization, the results of a very successful merger and optimal management of our research potential, building on the steady sales of our traditional products. We're very proud of this, optimistic for this year and ready for new opportunities. Thank you for listening.

Good morning. Hanspeter told you how we succeeded to post historic growth - very strong growth in 2003 and I will try and explain why this growth is indeed profitable. First of all, we increased our MBA (ph) by 3.5 times in four years before goodwill amortization. And this means an instant and sustained improvement of our net result over sales and this is illustrated by this slide, year after year, and has been true for the past four years. Strong growth of our sales plus 15.6% on a comparable basis and this year, the currency impact has indeed reduced this evolution on a reported basis. This is due to the U.S. dollar decrease by 20% in 2003. The growth on a reported basis, therefore is limited to 8.1%.

During 2003, succeeded to increase by 0.8% our gross profit ratio. This ends up with gross profit ratio of 8.3% with improvement - productivity improvement and also an increase of Plavix and other pro-U.S. royalties, which, however, was limited by the exchange impact already mentioned. At 2002 exchange rates, the royals (ph) of our gross profit ratio would have reached the 83.5% of sales. That is a 2% point increase.

2003 also sold 17.7% of our operating profit with a new improvement by (inaudible) operating profit of a sell (ph) ratio by improving our IMG (ph) expenses by 8%. That changed to 15%, 2003 by continuing our commercial effort in Europe and improving their best effort in the United States to sustain Ambien and Eloxatine and to launch Xatral. This year, we also saw a very strong increase of our operating incomes and expenses, down 13.5% due to the positive results of Plavix and Avapro, which we share with BMS all over the world. The share of profits paid to BMS and our main territory, which is Europe amounted to 173 million euros this year as against 140 (ph) million euros 2002. As far as (inaudible) receive 436 million euros from BMS as against 340 euros in 2002. And this is both strongly contributed to the imprisonment of our operating profits in 2003. This operating profit is indeed well balanced between Europe and the United States. In the United States, 44% has gained 42% for Europe in 2003.

Our net profit, financial income - 155 million euros, due to the hedging policy in 2003, given the low dollar position. Of course, our - this (inaudible) decreased globally the financial income from results. The income tax rate measures up to 33.9%, which was announced for 2003, therefore, perfectly in line with our expectations and our four-part for 2003. I would like to remind that 2002 was an atypical year because of right batch (ph) provisions and eight - we put a share of profits to a lower extent. This is (inaudible) interest, whereas in 2003, we eventually have no more minority interests.

Our net profit is therefore improved by 2.2% of our net sales of our -- net result of our sales ratio, which would be 31.5% at 2002 exchange rates. The - it is growth with four exceptions items and (inaudible) amortizations is 21.5%. In September 2003, we announced that this growth would be 20% on the basis of one euro equaling 1.10 U.S. dollar. We could have expected 19% of growth for ratio - one euro for 1.13 U.S. dollar. EPS, with four exceptional items and goodwill amortization is 2.94% euros. That is a 21.5% growth.

As far as - free cash flow - as this is concerned - we generated 1.303 million euros. We continued our buyback policy and acquired 20 million shares for 16 point - 17 million euros. We presently hold 36.6 million shares. That is 5% of share capital. Taking into account our stock options then, the proof is holding 6% of its (inaudible) shares. As of December 31, 2003, we have 2.4 billion euros in terms of net cash in hand, which is a very sound basis to prepare for the future. Thank you for your attention.

Good morning. We presently have 56 compounds and development to date. But more importantly, we have 18 - between 2B and to three phases. That is the most advanced phases. And the (inaudible) for our four major R&D fields of endeavor. On this slide, you will find each of this compound and given that I have a lot to tell you today, I'll like (inaudible) comment on this particular slide. What happened over the past six months? Well, we start to the Phase 1 printouts, which are CCK1 agonist (ph) (inaudible) is in euro, specialize in using authority. And therefore, printouts capable of simulating these receptors tend to reduce appetite. And this, of course, could be an interesting target for obesity.

That being said, we decided to stop research on these two compounds for two major reasons. First, because the efficiency over side effect ratio is not very good, especially because we have abdominal pain set off due to the varying mechanism of action as a compound. But more importantly, this type of compound indeed decreases appetite in healthy volunteers. But after chronic treatment of two weeks, the compound proved to (inaudible) selectic (ph), that is inefficient. And we, therefore, decided that CCK 1 (ph) receptors are not the right target for obesity.

Two indication of two compounds were also stopped. This one for (inaudible). Indeed toxicity, long-term toxicity trials revealed (inaudible). That is to say that animals lost some hair and, of course, this is not of great interest for anti-afflitis (ph) treatment. That is - that being said, the anti-proliferative (ph) effect is probably the reason for that. We will, therefore, continue developing this drug in the field of oncology.

Now, (inaudible), still talking about oncology, will be stop for non-small cell lung cancer. Here we have two Phase 3 trials, one positive and the other one negative. But the third one is not positive enough and this is the reason why. We need (inaudible) this work for phase indication, but we are continuing the Phase 3 research for hidden cancer because this compound is more active on hypoxic (ph) cells. Given that, for hidden cancer, this drug is being used in combination with X-ray therapy, the drug is more likely to be efficient. Three new drugs in pre-clinical development. One, synthetic (inaudible) separate compound for (inaudible) and (inaudible) is of the (inaudible) receptors, which could be of interest to treat many disorders in a (inaudible) of the schizophrenic patients.

More importantly, and this is worth something to dwell on - of those seven major results in well advanced trials. Five, in Phase 3 trials. And I'd like to present two results showing the efficacy of (inaudible) in atrial fibrillation. Results of the first Phase 3 trial for - buy-in and (inaudible) release and two, positive phase to be results for these stations with hyper (inaudible) as a (inaudible) factor. And two, the positive results in 2B results in major depressive disorders with an MTMK2 (ph). And now, the positive result with (inaudible) receptor antagonist in the treatment of F1ADH (ph).

What I'm allowed to tell you about - the life cycle of our compound. (inaudible) Plavix, we will have important results from the match trial during the second quarter of the year. And finally, we completed the inclusion of all our patients for the charisma (ph) trial. For our synthetic early growth (inaudible) Arixtra and hydrophynex (ph) are all perfectly on time.

And, of course, I'm going to report on the genetic results. Concerning the central nervous system, I'd like to say a few words about Phase 3 and 2b, that is an MTMK2 in the treatment of depression. In the field of oncology, I would simply like to remind that we filed, at the end of 2003, beginning of 2004, two important doses for Eloxatine, as in juvenile treatment of (inaudible) rectal cancer. And this is, of course, of major importance, given the nature of the results and given the size of the potential market.

Finally, in internal medicine, I will first report on all available results for Remonomin (ph). So, first of all Geneteron (ph). One year ago and following the GSN advice, we had such a new tolerance trial called Andromeda. There's a number of events with unbalance, twice of many events in this Geneteron group up against the placebo. So this is why there's an - we advise to discontinue the trial.

As they said, that both efficacy trials could be continued, as you know that when you start tolerance trial and continue efficacy Phase 3 trials, you have to realize that the compound is well diluted, but also has to be active. Otherwise, it would be unethical to continue a trial. And this is why we concluded that we had good reasons to be optimistic. First of all, we analyzed these clinical trials and deducted that there was no rational explanation for this imbalance. And that maybe this was quite fortuitous. And today, we continue to believe that this is the right explanation. So these are two favorite (ph) or Phase 3 studies, including 1,200 patients, one year of treatment. And these trials were conducted on both sides of their planting. These patients were patients suffering from atrial fibrillation or flutter and we measured efficacy of (inaudible) placebo.

The main endpoint for us to make an impact (inaudible) we're (ph), what are the (inaudible), either electric, that is shock, or from ecological or possibly this continues. And secondary endpoints were all symptoms associated to atrial fibrillation or flutter. These are the results that we obtained from the first year reduce, European trial, showing that after being adjudicated, that is after reviewing the ECT and noting that there were signs of atrium fibrillation, then a group of experts did adjudicate by saying that, indeed, there was a rhythm disorder or not. Which means that the (inaudible) proved to be very active during the first weeks and continued to be active with time. Which means that the risk of repairing decreased.

Also interesting is that we tried to find out what were the subjective feelings by the patient, whether they sensed this rhythm disorder or not. And we found out that the patients did sense this beneficial effect of the Geneteron and this from the very onset of treatment. And this remained quite (inaudible) over this one year period of treatment. It's also interesting to note that with the American (inaudible) trial, similar results were noted. We always requested to properly reproduce the results because when you have one year treatment by virtual trial, you have to compare results, which was the case. Since from the very first weeks onwards, we noted a recurrence reduction of 26% as against placebo. Likewise, we noted the same results as far as symptomatic (inaudible) is concerned. So very nice efficacy from the very onset of the treatment and this over the full treatment period, which is one year.

What about adverse events? Here you will note that on 12,000 patients, whether we talk of serious or benign adverse events, would have no difference versus placebo. More precisely, we have trend to which a reduction of adverse events on Geneteron. These stations are (inaudible) - 20% have part (inaudible) and coronary events. So these are cardiovascular adverse events. And this decrease is indeed the proper reflection of the efficacy of the compound. So this Geneteron indeed a very safe drug, especially if you consider that the 47% of the patients on placebo and 38% on Geneteron stop the treatment before one year. So this is a very active and (inaudible) drug, in particular, versus Amuderon (ph), which is the parent drug.

(inaudible) was observed in these studies. So, the drug proved to be highly effective for atrial fibrillation. Adverse events are similar to those observed with a placebo and, more importantly, no (inaudible) was ever described in these patients. Both studies are indeed very consistent. In other words, the pharmaceutical industry and (inaudible), in particular, are convinced that we are very close to reaching the conclusion. That being said, we are to meet with the careful (ph) parties to decide on this very good Phase 3 results for these two Phase 3 trials.

A few words about the aquaretic products. This is a diuretic that, which only eliminates water in urine, unlike traditional diuretics that eliminate as much sodium potassium as water. So how can a product achieve this? Well, in the body, there is a neuropeptide vasopressin and the other is the anti-diuretic hormone. So this anti-diuretic hormone, vasopressin, inhibits (inaudible) secretion of water in the kidneys. And the receptors - these V2 receptors antagonists - this inhibition -inhibition of the anti-diuretic is an aquaretic effect. And this is what we showed you previously in Phase 2A. We performed a Phase 2B study. That is, we compared two doses - 25 milligrams once a day, 50 milligrams once a day versus placebo in patients with an inappropriate secretion syndrome, SIADH.

These are patients who retail water be it for oncological reasons, hypersecretion of vasopressin because there's a constant urological original or cardiovascular origin. So, as of day two, you can see that there is a significant increase in anatrope. Why did we take this as an important factor? With water retention, there is hemodilution that there is dilution of the ion in the plasma, which is sodium. So this is a good marker for hemodilution. So when there is hyponatremia, there is too much retention in the body. And when we are below the level of 135 per liter, this is the case. You increase aquaresis water secretion, thereby increasing by several milli equivalents the concentration of sodium in the bloodstream.

And this is, as of day two, achieved with an effect - state of balance is achieved very rapidly and we did a 22-month follow-up with keeping all these effects - blue placebo, orange, 25 milligrams, green, 50 milligrams. When we consider the response rate, 15% placebo, it's close on 80% with a 25 mg. dose. And the only adverse effect obtained is probably logical - is that patients were thirsty.

Other patients have the retention, which is very localized. Cyrotic (ph) patients with this water retention, we use the two traditional martics (ph) - plasmatic, sodium and diuresis. This is a Phase 3 study. We compared a traditional diuretic Spironolactone and titration with our anti-V2 patients started at 30 milligrams could rise to 75 milligrams. The product is very active at 30 milligrams. Very few patients rose as far as 70. Placebo versus placebo not a considerable growth in diuresis with Spironolactone, but very important effect in the V2 with a plateau during the week. Similarly, anatrome was increased as of day one and remained on a plateau.

Furthermore, in the Spironolactone group from day six, we added, if need be, the anti-V2. When we add, in addition to Spironolactone, in addition to the anti-V2, we increase sharply diuresis and we thereby increase the plasma sodium level. The only adverse effect that we've obtained is a sense of first. So very well tolerated product that we are currently developing. In hyponatrome, the first - I won't comment this in detail. This is the sort of study that we're going to be starting before the summer in patients with FIDH, but I won't comment on this. This is a Phase 2B where we're comparing a placebo 12-5 (ph) once a day in cyrotic (ph) patients with acitites hyponatromy with no sodium variation and in the CTs recurrence. So very good results in Phase 2B with our aquaretic compound.

Let's now move to the central nervous system, starting with Ambien. A year ago, I showed you some results indicating the slopidem (ph) modified relief. Ambien CR had the same plasma peak as Ambien. That is, potentially, identical sleep induction with a half-life that was sufficiently long to have one to two hours additional sleep and no residual effect because the plasma dropped as from the eighth hour. This is what I showed you a year ago. In September, I showed you some very sophisticated studies where we looked at the residual effects - that how patients awoke the next day. We performed this study both in adults, in patients very sensitive - elderly patients. And we showed at a double dose in very sensitive patients, in elderly patients, that there was no residual effect versus placebo with a whole battery of tests.

These are the first results of Phase 3 in adults. We compared 12 five-milligrams versus placebo. After discussions with the health authorities, Ambien's the world leader. Consequently, the only thing the health authorities asked us was to demonstrate that Ambien CR had an effect versus placebo. A number of patients very high. It may sound strange. Over 100 patient because we performed a very considerable study, a poly-sleep study in sleep labs. These 200 patients, we considered what happened on the CT (ph), so it's very objective. To that, we added what is done traditionally - all the subjective scales, what the patients actually felt. And so, in patients with primary insomnia and difficulty with sleep maintenance. So, of course, this study went very well. The dropout on the placebo - a number of patients who dropped out - 10% -- it's at 8.8% with the product.

When we consider these objective poly-sleep criteria, be used the main criteria, the WASO (ph), up to six hours is the wakeup time after sleep onset. This was measured very objectively. The sleep duration sleep efficiency - this is a very traditional test. And then, sleep induction. That is latency to persistent sleep. And you can see that across these measurements and I'll show you an example in this - everything was statistically significant compared to placebo. Of course, we were expecting this, but all this very significant. So, it has an impact on sleep maintenance and it lasts six hours. Very little residual effect.

Sleep duration - very fine efficiency and latency identical to what happened with Ambien. In addition to these subjective - to the objective measurements, all the questionnaires, patients are, of course, fully consistent. And so, in terms of tolerance, very good tolerance - 52% adverse effect with placebo and it's 52 - about with the product major. Adverse effects essentially digestive. That's a good sign. And very little busyness with the products. This is a sort of result. This is what we obtain with WASO. This is the main criterion for sleep. Less than 10 minutes with placebo, a reduction of over 30 minutes with the product. Efficiency - plus five, 13% with latency, 13 minutes reduction, sleep induction, latency - 13, with the product, 24, with the product. This is of course, extremely significant. And it is all this. A year ago, we told you that we'd be filing this product in the second quarter of this year. More than ever, we will be on time and we will file, as expected, Ambien CR in the second quarter of this year.

Let's turn now to depression with some Phase 2B results, with an NK2 (ph) receptor antagonist. It's a neuropeptide. (inaudible) - we have obtained some positive Phase 2B - so in Phase 2A and I'll show you the Phase 2B results. In other words, to be is to find the active dose to launch the Phase 3 studies where we'll better determine the product profile. Of course, it's placebo, double blind randomized. In Prozac, Floroxidine (ph) controlled, to validate the study.

These are patients with recurring major depressive disorders. The medium score - AG0 (ph) in the Hamilton (ph) scale was 26, which is the illustration of what I told you previously. Very traditional protocol. Seven week duration, one week placebo and then six week treatment with the product or with placebo. We compared three doses of saraduton peroxidine (ph). The dose there is 20 milligrams. The three doses that we used once a day for saraduton (ph) - 30 milligrams, 100 milligrams and 300 milligrams, on the primary endpoint, which is the Hamilton depression scale. The doses of 330 are of the same order effective placebo. Whereas the 100 milligram acts like floroxidine, 20 milligram and the results are of a similar vein on the Hamilton anxiety scale. So, on the face of it, we have the dose for our Phase 3s. It's be 100 milligrams once daily when we look at the extended sustained response patients - 44% with the product and they're patients that we consider as cured, who have a Ham score level than (ph) eight, starting from 26 on average, between 37 and 39 of a similar order to floroxidine.

A few words on tolerance. You can see that the adverse effects are relatively traditional for floroxidine, essentially digestive gastrointestinal disorders, nausea which - it would appear that saraduton is best - better tolerated at this level. Likewise, for the CNS disorders, the adverse effects - dizziness and the product seems to be better tolerated. So, potentially, with this product, we have a second product that we will send into Phase 3 before the end of this year. It's the second because we have - underway, Phase 3 launched another product, which is a three (ph) antagonist. We know that it's a difficult area. There's no need to remind you of what happened for the industry with the NK1 antagonist. But what makes this very optimistic is just this statistical approach. To my knowledge, we're the only company that has two products - (inaudible) three and potentially (inaudible) two in Phase 3 in depression. And if we don't put all our eggs in the - one basket, one of them will come through.

We had three other targets in development today - NTV1B, anti-seria (ph) - will be FH (ph) and (inaudible) we had finally products in development in the field of depression. One or two will, at the very least, come through. Let me end with giving you an update on the results with Remonibando (ph). The complay (ph) of this is a very important Phase 3 programs. We have seven studies including over 13,000 patients, half in obesity and half in smoking cessation.

Obesity is the only area where the FDA guidelines require two years. Follow-up - that's why today I'm only giving you the initial results of the first study that was completed - one-year treatment - and that we'll have all the results by the end of the year. Across these four smoking cessation, I'll give you the first results in smoking cessation's stratus U.S. - 10-week treatment in the U.S. And we'll have the identical results for Europe and the one-year treatment results on the maintenance of smoking cessation induced by Genomivent (ph) or Complier.

First, smoking cessation. It's important to note that the number of included patient is quite high. We compared placebo, five times a day, five milligrams per day, against eight (inaudible), 20 milligrams a day. The primary endpoint is cessation between weeks seven and 10. Of course, this abstinence was measured not only the basis of clinical criteria, that his questions are actually reservations (ph), the wholesale biological criteria. That is measurement of (inaudible), which is the nicotine metabolide. And these measurements were made because when (inaudible) claimed that they quit it, are lying. These patients are very poorly compliant. And this is also the case for these patients. In smokers or these patients, compliance is very poor.

This wasn't always the case in previous trials, but here we decided to support clinical criteria with biological criteria. Of course, the primary endpoint is sustained abstinence rate during the first week and, for the full population, we move from 16% on placebo to 28% with Complier. For the completers, those who have complete the trials, it's approximately 1.6% placebo and 36% on Complier. Of course, all these effects were found to be significant versus placebo.

And now the essential point for smoking cessation that all smokers know about perfectly well. As soon as people quit smoking, they tend to gain weight. And this is one of the reasons why people refuse smoking, especially women, for reasons which are self flattery. Looking at the whole ITT (ph) population, we see that there's a weight gain of more than one kilogram placebo with 300 grams lost on 20 milligrams of a dose of Complier.

We also decided, given that this was an American trial and given that some individuals were slightly obese, so we also considered none of these patients. None of these patients who quit smoking gained three kilograms. So this is a very significant effect, which is not thoroughly an anti-obesity effect. What about side effects and adverse reactions? First of all, it should be said that the drug is very well tolerated. We had a 28% dropout rate on placebo - 30% for a five milligram dose and 28% for a 20-milligram dose of this.

So there's no difference versus placebo as far as the dropout rate is concerned. As far as all side effects or adverse reactions are concerned - no difference. It's absolutely identical to placebo and most of side (ph) patients were very poorly compliant. Patients showed very benign side effects, mainly digestive side effects (inaudible) which disappears for a time, plus some minor psychotropic adverse events, which are extremely difficult to differentiate against cessation syndromes. That is slide anxiety or stress. This is a nova (ph) adverse action, which was observed. But this corresponds to 1.5% for placebo patients and 2.3% for a 20-milligram dose.

So with Complier, we do have a compound which, in approximately 800 patients, that proved to have a very clear cut effect versus placebo without any weight gain and with a very good tolerated (inaudible). These are important and this is (inaudible) was requested by the health authorities, both from (inaudible) and (inaudible) smoking cessation treatment, was to look at psychotropic effects, but also cardiovascular effects. As far as psychotropic effects are concerned, we used the HAD, that is hospital anxiety and depression scale criteria to find out, if possible, the effect on anxiety.

And you see that versus placebo, whether it would take the depression sub-score or anxiety sub-score, there's no difference whatever between a Complier and placebo - another essential perimeter for health authorities, which led us to conduct a very detailed trial that concerns possible effects on cardiovascular behavior. No difference on systolic or diastolic blood pressure. No impact on heart rate and no effect on the QCB. So the cardiovascular tolerance of Complier is similar to the placebo. So these are the primary results of (inaudible) Phase 3 (inaudible), proving that this very active and well tolerated compound.

Let us move onto the ryolipids (ph) study, which was conducted over one year, including 1,000 patients and more. Patients were - had 34 mass index at the - not the (ph) mean weight of 95 kilos - true (inaudible) the patients with true mobility factors and fairly high hypoglycemia. Recovery endpoints, of course, were weight, on the one hand and waist. You see that the drug led to a very significant weight loss, virtually nine kilos over one year and a dose of five milligrams, resulted in four kilograms more weight loss and two - up against two kilos on placebos, a small than highly significant with P value (ph) of 10 minus 30 for this 30-milligram dose.

It's also very interesting to note that the drug has main - has an effect on the visceral part. As you know that cardiovascular risks very much depends on visceral part because these - this is where the risk is the highest. And we have four centimeter reduction in waist on placebo with a P value of 10 to the power minus 30. This true parallelism between those two criteria that is weight loss and waist. So the efficiency of the drug proved to be very, very favorable indeed.

But is also often requested by health authorities - the two falling barometers. The number of patients who have a weight loss above 5%. And you see that in the overall ITT population, we have moved from 19.5% to 58% placebo and Complier respectively. And for one year of treatment, we've reached virtually 73% of patients with more than 5% weight loss. Even more important and more illustrative of the phenomenon, if you take those patients having the weight loss above 10%, whether we considered the whole population or just those patients who continued the treatment until 12 months, we move from 16% to 44% respectively. Forty-four percent of those patients who've been treated for a year lost more than 10% of weight, which is most highly significant.

I would like to remind you that these results concerned these patients with core mobility fracture, mainly hypoglycemia. And of course, we had to measure the lacitic (ph) barometers as well. The (inaudible) has no effect on the global cholesterol rate. It's not a simplistic cholesterol inhibitor. However, it has a very significant effect inasmuch as it induces the increase of HDL cholesterol, which is the good cholesterol, which is 20% increased versus placebo. So the drug has the effect of increasing HDL cholesterol. Likewise, it significantly reduces the triglyceride rate, which turns serum into (inaudible) serum. So this is not a simplistic (ph) cholesterol inhibitor, but has a very important effect.

And when these barometers are - or variations of barometers are related with weight, we see that a dose of 20 milligrams - whether we talk of (inaudible) increase or decrease in triglycerides, 50% change does not depend on (inaudible). This means that the drug has an effect, dependent on its central effect, but the effect is a direct peripheral effect on (inaudible) tissues in particular. So it has no effect, but is dependent on (inaudible) barometers.

Most of these stations are to be considered as pre-diabetic patients. They're not well equipped to withstand sugar overload. So we decided to provoke hyperlipidemia (inaudible) at (inaudible) and then we would measure the difference rate two hours after having induced this sugar overload. And we see that Complier induces a very significant effect and reduces glucose response. In other words, these patients are becoming more likely to properly react to glucose overweight. This might be partly explained by better (inaudible) to insulin. When you inject glucose and when it goes - the glucose overload, the body reacts by secreting insulin. And at times, insulin reactions are not adequate. And this is the case for most obese patients. There's a very significant versus placebo decrease that showed that the compound is able of increasing the sensitivity of these patients to indigenous insulin.

A new concept emerged over the past years, which is called the metabolic syndrome. This is the expression of a significant cardiovascular risk and at least three of the five (ph) the criteria have to be met. Abdominal adversity with high waist circumference, hypertension, hypertriglyceridemia, a low HDL cholesterol or abnormal fasting glucose that is a poor adaptation to provoke the hypoglycemia. So, considering these criteria, we observed that 50% of our patients were suffering with - were presenting with this metabolic syndrome.

After one year of treatment, we observed that only 25% of these individuals still had this metabolic syndrome. What about dropouts? Thirty-eight percent on placebo, 40% for a five-milligram dose, 36% for the 20-milligram dose. This is less (ph) than placebo. But here again, it has to be emphasized that obese patients are poorly compliant. This is a fairly long treatment and you see that compliance is virtually similar to the placebo patients. As far as side effects are concerned, we move from 2.3% for placebo and 4% with a compliance (ph). As far as dropouts are concerned, it should be reiterated that those patients are fully compliant. For gastrointestinal events, we have same profile as what you get for (inaudible). Roughly, we move from 2.6% for 30 milligrams Complier as far as - and (inaudible) are concerned and 30.6% of the (inaudible) to 1.6% for Complier. So here again, it should be emphasized that the Complier is well tolerated and this (inaudible) be considered difficult patients.

And in a more - important for V stations (ph), using the same psychotropic criteria, we have no effect on the depression sub-score nor anxiety sub-score. For cardiovascular impact, we have no effect on arterio-block pressure, although maybe in untreated hypertension (inaudible) Complier could have some minor effects. There's no effect whatsoever on heart rate nor on (inaudible), meaning excellent cardiovascular tolerance all together.

To conclude, we may say that Complier has essential effect on rewarding (inaudible), as already mentioned, but also it has a peripheral effect, which has to be emphasized. And certainly, our major investigators are about to submit, beginning of March, to the ACC the results of these two trials. (inaudible) is one of these investigators and you will then understand why these Compliers have very interesting effect, centrally and peripherally. The evolution of the different tissue has evolved considerably. It was always considered as storage tissue, but lastly, it was demonstrated that (inaudible) performance and the (inaudible) tissues could have very interesting effect as well.

So, I would urge you to listen to the presentation of the results at - which will be submitted to ACC and you will have results to (inaudible) station and capacity. So, this is the first antagonist of (inaudible) receptors, which have an effect on obesity, on (inaudible) receptors and also on (inaudible) station. Which means that if it were to reproduce all these results, knowing that the results will be available at the end of the year, this treatment could become first line treatment for a patient presenting with cardiovascular risks. I'm afraid I've been extremely talkative. That being said, it's quite rare to have so many free results to comment. That being said, out of these six Phase 3 results, five of them are indeed positive and I have the feeling that I'm indeed quite fortunate to be able and present these results. I'm also very fortunate to work with magnificent team of researchers who are capable of generating these results. It's a true pleasure for me to be able and present these results to you. Thank you.

So, by way of conclusion, well, we must begin by concluding on this year 2003. It's clear that the year 2003 is very much in line with previous years, the past four and five, in particular. I'd like to very soon return to strong growth. Without strong growth in our business, the future is uncertain. Sustainable growth, that is the new product portfolio must be regularly fed into in addition to what already exists today. (inaudible) shows that our company is based on sustainable growth, profitable growth, all the factors, all the ratios.

You have seen a positive once again this year. Positive not just by saying that had the dollar not been so unfavorable, we would have had positive results. No, it's with the dollar as it is versus the euros. The results are very positive. And of course, if the dollar had been more favorable, they'd be even more positive, but they are positive. Whatever the dollar rate reasons for this strong company, this very strong platform, for a number of years is, of course, a strong and productive R&D across the industry with a few exceptions that this research is viewed as extremely productive. There's no argument about that.

What is left (ph), clear, possibly is if the results - this famous strong growth is achieved, why are we achieving between 15 or 20% growth when others are posting less than six? I believe there's a genuine reason to that. It's that (inaudible) research. It's not a matter of having high expenditure to achieve results. What is in the life of operations, in the day-to-day operational management. It's not the number of medical representatives or sales and promotional sense that counts, but the result and growth and that requires a work of motivation, organization, focus on people, focus on the markets, an efficient organization that generates between 15 and 20% profit. Yes, R&D is very productive in this company, but the operations - all operations, combining, of course, production, production in sales, extremely positive to very specific. It is market oriented, market focused, efficient because it is market focused. It's not theoretical. It's in the field.

And also that this is slightly more difficult, possible to say that you'd have to ask people in the company. This company has a long history in terms of employee relations, the mindset attitude through strong supportive teams and something that is, perhaps, even more important is that every time we're in a country, we're in a different culture. And when we're in a country, we have, first and foremost, to respect the culture in the country to be able to lead people. And there's no denying that in this company, we want to be Brazilians in Brazil, Mexicans in Mexico, Americans in Germany - in the U.S. and German in Germany.

Why strong basis with such results? To go even further - we want to go even further because for a company that was founded from scratch in 1973 achieved this 30 years on, is (inaudible), but there's more to be done. We're not allowed to attempt to do better. That it's this - this plan, the (inaudible) offer for Aventis is a strategic. To go even further - why? Because the world is changing. And in today's world, it's true that you have to be stronger, even stronger to be able to meet the increasing R&D spendability to develop many more products.

And you can see that there's a very considerable R&D portfolio. We can do more, faster and better because the battles in the field, when we're on highly competitive products. And we want to defend all our products, including the mature products where we need people - motivated people in the field. And that's why, to create the number one in Europe and the number three worldwide has - makes genuine strategic sense for both companies.

Of course, this future company will be strongly present in Europe. In Europe, especially in France and Germany. It's true, but no one is criticizing a U.S. company for being strongly present in the U.S. because it has its headquarters there, because it has its R&D facility there. We will be a company with a strong presence in Europe. And far from being something dramatic or being strongly present in France and Germany, it's an opportunity to have a strong presence in one's home market because we'll have our head office there - an important part of our R&D and our production facilities.

Once we've said that, well, the market in this business is a global market and you need to be global. Well, what does that mean? It means being everywhere and fighting everywhere and the U.S. market is the number one market. We have to fight in the U.S. market. But it would be a major step forward and it would not be, going back for this company to merge the two companies. You've seen the growth rate. You seen that without that side of (inaudible) in 2003 has priced at far and away the highest growth rate in the U.S. market with volumes that are becoming increasingly important. To merge these two companies, to pave the way for future launches and better defend existing products is a key point, including in North America.

Yes, I believe there is need for a development strategy that is very international. To say that only the North American market it important and the European market, possibly, means what? Means 20% of the world population. That leaves 80% of the world's population that is the future for after tomorrow of this industry where we have to develop and grow. Hanspeter said by (ph) the years. We're very proud to have a growth rate of above 20% and the rest of the world, all the territories that account for 80% of the world's population, to have a growth rate that is twice that of the market, seems to me, for the future, to be a very and extraordinarily positive development.

So this is what we seek to achieve, to go further. How can we have - how do we go about achieving strong growth? I said this earlier. We need to apply a strategy that needs to be implemented rapidly. Mustn't spend months discussing what we need to do. We know that the world is changing too fast. We can't allow the uncertainty. We need to have a clear project to sign up to it, to know what needs to be done. This is what we are proposing. To have strong growth to achieve this famous strong growth, which is the key to the future. We need a policy that is appropriate to each country, for each country, each product. There is no small country, no small product. That's how we win and that's how we achieve strong growth.

Now, of course, in combining the two companies, combining marketing and commercial resources, of course, we will accelerate the growth of major products. No question about it. Of course, we'll better defend the mature products which we mustn't discard and optimize the launch of future products of the combined group. And in the - what R&D gives us in terms of perspective, there's some very fine things that require resources. So this R&D is a key to sustainable growth. Strong growth is vital. That's how we generate the bottom line. But at the same time, we need sustainable growth. We mustn't cut back R&D when we have projects to defend.

And here, by focusing, by combining the resources of both companies, they need to be concentrated on the best projects of the two groups. But what are those best projects? It's difficult to make a judgment, but they're the most innovative. From time to time, we - the past 10 years, we've criticized (inaudible) R&D, to look in what was too innovative. So from time to time, we give a bit more time. I'll read that. A bit more time is spent in Phase 2, when we copy other people's products, it's quite easy to move fast. When you genuinely want to innovate, it's more complicated because you have to seek out the therapeutic areas in which the product can be effective. And the past few years have demonstrated the talent of R&D and have (inaudible) people to achieve new breakthroughs.

Peperin therapy, platelet aggregation for thrombosis - he's inventing the product against the poor metabolism or the bad metabolism. I don't know - but there's a concept around this (inaudible) that is radically different. We need a novelty product. That's - it's our business. And when he's in the central nervous system with that very long list of product 2B and three and everything in 2A, there's a whole slew of innovative targets. We need innovative products because we don't create a great difference in the therapeutic areas. And that's our business. Of course, we must select, by combining the two companies, we'll focus them on the most advanced projects. It's all well to say in 10 years, five years hence, I'll be very good, but we know.

One of the old sayings in this company before - looking ahead 10 years, let's get through next year. We've been doing this for 30 years. We need to focus on the most innovative products, but to the most advanced projects because those will allow us to go even further the following year. You have to live the next year to be able to live in five year's time. The most promising - what are those? Well, of course, it springs immediately to mind that we need major products. When we talk about registering of product at $100 million or euros, others between 500 and one billion. At one billion and those with the possibility of five billion. Not all projects are the same, as you know. When you enter these projects in the same - in your models, you don't give them the same value.

The most promising - there are those. And the company has also faster tech, for instance is an extraordinary project - an extraordinary life-saving product. Not with gigantic sales, but it's a fundamental product for treatment that saves human life every year, every day, every week. Those are the most promising products. We'll continue to battle in those areas by focusing, combining the resources that are huge. The sum of the R&D spend to both companies should generate many innovative advance and promising projects.

Profitable growth - well, to do many things, you have to earn a good deal of money. I've said this for 30 years. The company is there to allow men and women to live, but our shareholders lend us their money so that we can do what we seek to do. And in light of that, they need a payback because they place their trust in us. That's the deal. And then while no company can be sustained one at a time, can reward its shareholders if it is not profitable. We need profitable growth. Earlier, I showed you our EPS growth rates. The first five years is the history of profitable growth.

So the new company needs to be in that state. In the interest of all shareholders, the shareholders of both companies, both groups. We know that without profitable growth, there is no capacity to invest either in R&D or in the production or in promotion. When we don't have profitable growth, what do we do? Well, we cut R&D spend. We cut sales force. We cut back on everything. That policy is not a motivating policy for groups, of course, in the interest of the employees. We must achieve all these optimizations. It's resource optimization is a continuous process, of course. But if that's all there is, without growth, without development, it is extremely difficult to motivate people and we're likely to have - end up with people who are sitting down rather than people who are running forwards. But the need for profitable growth is important to generate both for employees and for shareholders rapid growth, which is the key to success.

And lastly, serving the interests of patients. (inaudible) could say this better than I. We need very profitable growth to achieve a lot of research. It's a project I won't return to. We've discussed it at some length. Sustainable, strong sustainable, profitable growth. That's the starting point. If we don't have that, we won't achieve it. We've placed some of (inaudible) in that state over the past year. The next one's a new organization, must have strong sustainable and profitable growth where we need to get the project underway rapidly - not one year or two years on. Still be redefining the strategies, the policies, who does what, who needs what. Hence, the need to rapidly implement this. And there is genuine respect in the way in which organizations are set up.

To say that pluralism is dangerous, just simply amounts to not understanding what a genuine organization is about. We mustn't break mindsets and histories. We must draw on these pluralisms, on this rich heritage. It is - the various heritages constitute our wealth. It's not a matter of just having one head, one voice. It's the best way of getting it wrong. The future organization is like the existing organization, but more - so the future organization will give considerable place to pluralism, which is a source of richness.

Only the respect of culture - and I'm thinking here particularly of local cultures. Only the respect for cultures and specificities is a major source, a motivation for a clear strategy and yes, there are things that are patently obvious - to focus on a single culture is really a tragedy in today's culture. To respect cultures both in terms of sales promotion - that goes without saying - but also in terms of research. Of course, in the U.S., we must have research, but we need to have research in Europe. The talent of the Europeans is not the same as the talent of Americans. And (inaudible) would explain this better than I and would say that he's not looking for people in England, not to - the same as what those who are research in Milan or in France - that's why he's very pleased to have the prospect of an important research center in Germany. Territory where we have no research, there's plurality is the genuine source of richness.

Let me repeat the offer - an offer than is balanced. Look at the major investors with Aventis who are saying that it's not - the price isn't high enough and those with Sanofi who are saying that you're paying too much, you're premium is too high, in terms of the value. That's the problem. That's our problem - how to find the right balance so that the two shareholders, the two groups of shareholders of Aventis and Senopy have what's right for them. You've put the same - the two companies on a (inaudible) - the same level a year ago. But not for with a premium of 15.2%. What are we brining the Aventis shareholders? Well, of course, a rich portfolio. That's unarguable. I mean, even it can't - can be sought forth (ph) for reasons - a sign in terms of substance. There's no argument that we're providing quite an exceptional R&D portfolio. The ability - a way of generating the results that you've seen here.

And in particular, in terms of our business, is a contribution for Aventis shareholders and for Sanofi-Synthelabo shareholder there will be earnings accretive from 2004 and combining resources to accelerate development of existing the future products from both groups. Thanks to the calling of combined resources, there's no doubt about it. But if we consider what this new group will look like, well, strong, sustainable and profitable growth - that's what needs to be developed. And of course, if we manage to do that, if we succeed in doing that, as we have some ideas, as we have done in the past, then I believe we are genuinely with a project that creates value - value for all. That's what I wanted to say in conclusion.

So, we're now going to answer your questions. I would ask you to introduce yourself before putting your question and please don't forget to stand up.

Chair ladies and gentlemen, good morning. (inaudible) from ING. A few questions, if I may. First of all, the filing date for FTC - I'd like to have some more details about that. My second question would be on the synergies that you do expect - 1.6 billion. And resurfacing costs amounting to two billion, which you announced when announcing your offer, given that you never in the past decided to reduce headcount. Now, to take stock on the Aventis negotiations, that is third, lastly, that (inaudible) of all possible links with other partners. Could this cause you delay - the offer?

Now, it's already your fifth question, sir. So we might take them one after the other.

My last question is on (inaudible). This is a question to (inaudible), rather. Ambien CR - what is your feeling as against Atoplan MR (ph). Do you intend to conduct a head-to-head trial with Atoplan MR?

Well, I might start on Atoplan, if I may. The answer is clearly yes. As soon as the drug is marketed, we will obviously conduct an Ambien CR -Atoplan trial. One year ago, we announced that we would file, during the second quarter of 2004 and this is precisely what we will do. We won't have any delay.

Now, might - a few words on changing control. This is going to be a multiple answer. According to our experience, it's not likely that a license could be withdrawn if Aventis is a true venture into larger scope. This is also confirmed with the Genza (ph) license, which was granted to Aventis and they stated that there was no impact of this merger on the deal. That being said, if we have change in control places, that they will be supported and accompanied by offsetting classes. So if it is an important subject matter for Aventis, we will wait for their reactions on that.

A few words on the recourse, which was filed on Aventis on the receivability of the offer. We might express our surprise, especially versus the Aventis shareholders who will gain from the offer. That being said, we do not know about the details of this recourse and, more importantly, we do not know about the reason of this recourse. That being said, we're extremely serene and we won't change the offer closing date, which we had planned and of the first half of the year.

As regards the FTC filing, well, if you want some more details, you may refer to what has been written in forward the first FTC contract, et cetera. Also, I would say that the preliminary steps have been started in conformity with the applicable regulations. If you would have more details or put more precise question, of course, you may do so, but the procedure is underway and I might then turn to the person in charge to answer your question, if at all you want to place a more detailed question on that. Synergy is 1.6 billion worth of synergy, part of which is positive, a part negative. We said that there was one set of positive synergy, two-thirds of negative synergy. I don't know whether this has been said as explicitly, but this is the right order (inaudible) in a way.

Then, the arguments that are put forward by some observers is that this will result in a terrible social breakdown. While we have 70 countries and 70 Sanofi-Synthelabo headquarters, 70 Aventis orders, but all that will have to be tailored to product in countries. Then, as far as manufacturing is concerned, I have no answer except to say that we have permanent growth requirements because with such growth we have to produce drugs every year, which, of course, is slightly different when you grow only by 6% and then you have the major headquarters, the Sanofi-Synthelabo headquarters, which are not that enormous afterwards. And then the Aventis headquarters disseminated between Strasbourg, Frankfurt and the United States. Maybe this has to be streamlined. As far as cost activities are concerned, obviously, a number of elements will have to be considered in terms of consulting, in particular, in terms of contracts. A lot of contracts and our experience tells us that research contracts are indeed very expensive. So these contracts might end up in a number of drugs on our listing, but not necessarily good ones.

So, I'm personally convinced that these problems are of great importance and can be properly dealt with if they are first dealt with, with the trade unions to come up with the best suited solutions. I never said that I never conducted - had cost reductions. We did close France and we had to reduce headcounts. But we did sell, trying to create in the best possible conditions for our employees because then a special dialogue is broken. Obviously, this does not lead to proper impulse in terms of a certain development - a certain development is essential as the setters (ph) go through discussion with our (inaudible). You also - well, about synergies, in particular, because the 10 or 15 last search offers, we were on the average. Do you consider that our restructuring costs are too high? I don't think they are. Restructuring costs are also in the average of the industry - two billion may be considered as quite consistent.

All this will have to be considered in a fast worth time. Some said that we announced more than what we did. My answer was that, over the past five years, we always delivered more than what we had actually promised. This is not enough reason to take useless risks. I think that the offer we made is the right commitment and you may be sure that the commitment will be abided by. Well, I'll try and be short.

Back to the premium that you announced, which is 15% and which is exactly what you announced at launch. But today, the Aventis (inaudible) rate is above you have proposed. You also said that some investors considered that the premium was too high and that the other part of investors considered that it's too low. I'm one of those who initially considered that it is too low. Well, we need defenders on both sides. We did announce this 15.2% premium. That being said, the market considered that no premium was even useful, given that the companies had been considered equal for many years.

Now, we have all these speculations taking place today. I think it's not fair that the prospect of the emergence of this white knight might lead to increase in the assessments. All the investors that we met with over past 15 days, were announced that the Aventis results would be received in February, that the Sanofi -Synthelabo results would be announced on the 16th of February and that, therefore, all pertinent comparative elements would be available to assess growth to assess sales, to assess operating results, et cetera. And to assess the value of the (inaudible) and met in the long-term for both companies. I do believe that from today onwards, the analysts will avail all pertinent elements to come up with a final assessment and we'll wait. I really don't see why this offer would not be perfectly fair and balanced.

When I'm being told that company A had to offer that amount for that product, yes. But the value - the value of the sales might have been slightly different and here I don't see good reasons to compare premium. What is important is comparing the worth of the companies.

Good morning. My name is (inaudible) from (inaudible). Could you please tell us - yes, I'm here. Right at the back. So, you did - you do confirm that you have no intention whatsoever to increase your offer. Could you please give us some details on that?

I confirm what I had said this morning and for the past fortnight that the market needs to be clearly informed about the results of 2003. I did, to its model of previous years look at how the results are constituted, what the short, medium and long-term portfolio looks like. And once the market has considered all that, that market will form a view. At the end of the day, it's always the shareholders who form a view. So I have no other comment to make today. And that I said this morning. So I stick to the comment I made this morning.

(inaudible) - three questions for (inaudible), if I may. The first on (inaudible). Without prejudging discussions you'll have with the regulatory authorities, do you sense that with the clinical data you now have, you could file, without further clinical trials? And on Accumplia (ph), could you perhaps specify the filing date that you're targeting? And on the indications, just to clarify - the concept - the metabolic disease concept, do you, targeting prevention of diabetic risk factors? Thank you.

Well, on Dranida Roan (ph), I'll disappoint you. The health authority isn't quite rightly very punctual. We never make a comment as long as we have neither - not talked to the health authorities. Very sorry, it is that I am - it's not that I don't want to answer, but I'm not allowed to answer. For Andromeda and more recently, we have two positive efficiency studies with very fine tolerance. So from there, we'll share those results with the health authorities and we'll await their feedback. We don't want to preach that. It's always bothersome if we start trumpeting it. Then there's always a backlash. We never comment on that. You'll forgive me.

On Accumplia, as we said, we seem to be on time. We'll have all the results by the end of this year, early next year. So we plan to file, in Q2 '05 on the claims. Wait until we have constituted the file before saying that we'll have such and such a claim. For the time being, we are indeed very optimistic. We're also very optimistic on the reproducability, but we'll see in due course. So forgive me. Every time it's a matter of health authorities, I can't be too specific.

(inaudible) Securities. In the document of your offer that it would lapse if the U.S. FTC were to initiate a request for further information, such a request is not uncommon. What's the risk of pulling your offer in the event of such a request? Second question, if, after your offer, only - just over 50% -- say 51% of Aventis shareholders bring their shares, how would you manage the situation. And a question for (inaudible). In the saraduton (ph) results, I didn't find a small - the statistic significance. And final question for (inaudible). Of expenditure and income, of the alliance with BMS, it's the bulk or the other factors to be taken into account under that line?

On saraduton, generally, in Phase 2, no significance. The anti-V2 (ph). It's - be - I don't know how many is in the (inaudible). The B (ph) is at 0068, to be absolutely specific, but the aim of a Phase 2B is to find the dose. There's not doubt that 100 milligrams, the same order Foroxotine (ph) and 30 and 300 are not different from placebo. So, it's a question of number of patients. We plan a program that will discuss, with the health authorities, Phase 3, it's 100 milligrams now and it's at that stage that we'll know the true profile of the product, both in terms of quantitative difference, but also qualitative on the activities, on the adverse effects.

On the question of if you have more than 51%, I mean, that's the question. If we want - that's what we're asking for. If we wanted 50% plus one share, it's because we believe that 50% and one share will manage. Is that your question? Will manage well. I understand where your question is leading, but let's wait for events to develop. What we're looking for is 50 plus one. (inaudible) on this - on the FTC point.

On the FTC, Brussels as we said, we had preliminary contacts before launching the offer. Now, the study that we performed - that is to believe that we would essentially encounter one problem. Today, I'm unable to tell you whether it is one problem or more than one problem that we'll encounter because the files have not yet been submitted. I'm establishing a parallel there between FTC and Brussels. But one problem appeared to us as manifest and that's the market position of Levenox in the U.S., 90% in Arixstra, one percent. So a problem to be resolved there.

Reason why we started the divestment process, we announced this on the day of the announcement, so the - that's the problem that we're anticipating. And even if the work is not completed, far from it with FTC, we are reasonably confident that this remains limited to that products at this stage. We do not anticipate that we won't successfully resolve the problem in the first phase. So we do not believe that we - risk that we - on the risk of moving into the second phase, never be sure. But we are reasonably confident that we'll be able to close the offer once the first part of the process has been completed with the FTC.

Just to handle your technical questions on the other incomes and expenditure. Profits with BMS represent 95% of that item in '02 and '03. Giving you all the numbers that I gave you earlier, you can readily track the development of that item - 2004.

The - there are no disposals of products - capital gains. It's the result of the growth in sales and productivity gains that leads to the net and earnings per share.

Japanese Economic Journal. Two questions - on the Japanese market, you said earlier that you have changed your dealing with Tosho (ph). But you have a relationship with Daichi and Fujisawa. Do you plan to change that relationship? And once you have succeeded with your takeover bid on Aventis, how will it change your business model in Japan.

Well, first question, yes. Partnership with Daichi will change. You know that today, we are in a license contract, with the revenues, we're licensed. And tomorrow, with the Plavix (inaudible) launch, there'll be a joint venture with the - with the consequences that entails. That is, that we share the revenues and the investment 50-50. In terms of Aventis, it's clear that one of the strong points of this is direct access in Japan through the existence of Aventis in this market. It's a very attractive proposition. It part of the fact that today the Japanese market has somewhat lost its attractiveness. I saw that the growth projections this morning remain very modest, but the presence of Aventis is important and it's an important asset in this program.

For several years now, I mean, we decided, you know, that a joint venture with Daichi, Daisho (ph), Fujisawa and others (inaudible) are joint ventures by product. And for several years now, we have decided to set up an important department for clinical development and product filing in Japan so as to keep the future products for ourselves, looking for a direct operation, direct base, so things will evolve normally in the future. Major products of the company will be able to more directly and easily enter the Japanese market.

(inaudible) - three questions. The first question is could you, perhaps, quantify the number of product duplication, in terms of sales? After a merger with Aventis in front, we know there's a lot of product overlap. We're not talking major products. Small products - Evoman (ph), Stilknox and there's a slew of others. Could you, perhaps, quantify?

Two to 3% of sales.

OK. Thank you. Ambien marketing study versus placebo - how are you going to differentiate Ambien MR (ph) compared to existing Ambien. What's the marketing strategy to differentiate products there? Question number three - you mentioned mergers with ZP Pfizer (ph). That was a merger between partners. I'd like to know why you didn't look, consider another candidate other than Aventis or one such as you existing partner, for instance.

(inaudible), if you take Zophidan (ph), please.

Well, yes. I mean, there's no question of positioning Zophidam MR versus Ambien - Ambien CR versus Ambien. What we told you at the time and what I can confirm is that Ambien is almost an ideal product. Sleep induction within 20 minutes, wake up next morning without residual effects. The only small things is that 20-25% of patients would very much like to sleep one to two hours more. So when we sought to find a new formulation after Ambien, we kept a product that has the same sleep induction latency and this is what happened. We demonstrated that successfully in the duration. You saw that on maintenance. Very objective perimeter, which is the WASO. The product lasts six hours.

Few products have been tested that - have been tested with those factors, but with the WASO, in objective positions, when we look at the EG (ph), that Ambien lasts a little less long without residual effects. It's not positioned compared to something. It will be in addition to - to that is added because for a year now we've been telling you that we're on time. We'll be filing Q2 '04. If you add a year to obtain the MDA (ph), that means summer 2005 and the Ambien patent goes public in 2006. So, Hans Peter's team will have ample time to consider that.

It's not mine. Sorry - sorry to disappoint you, but you - but it's really that of Hanspeter. Don't divide them. They are twin brothers - Ambien CR. I mean, it's a tactical option that leaves us with a lot of opportunities. The profile from (inaudible) is that you take Ambien for a New York-Paris flight. If you take - if you're flying from Philadelphia to Paris, you take Ambien CR. I mean it's a little primate, but that - it's the marketing positioning. Of course, there's a protection of that form, which will be extremely enhancing and it leaves open some pricing and discounting options in due course. But we really have to see what's happening in markets. There are two entrances looming, but we - now, in October 2006, we're keeping that as last minute tactical options. But the substance, as (inaudible) said, it has a mode of action of one-two hours more.

I'll answer your question, but it's the nth time that I'm answering press media radio in public. Yes, of course one can always say that you should have. When we're launched in something, it's because we believe that it's an extremely important opportunity, an opportunity that can be fundamentally a win-win opportunity to forge a great European group, anchored in Europe, well established in the U.S. and rest of the world, is a sort of originality that can make it something very attractive for shareholders and investors alike. And I believe that this project is a good project, so you say, if I read you correctly. Why did you not do something with BMS? We didn't do something with BMS because we felt that, given the current state, that thinks that it was a fine project between Sanofi-Synthelabo and Aventis. And we're offering this one and we'll fight for this one.

(inaudible) - you told us there were new minor drugs at Sanofi-Synthelabo. As far as Aventis is concerned, they do intend to have minority joint ventures. Well, this is not at all what we intend to do. We do not want to give up such a significant (inaudible) if we want to fight in all countries because some of these drugs are also very, very central for some countries. Of course, this is not at all in line with our (inaudible). Communicated (ph) goal - three questions. Two on your drugs and one financial question. On your drugs, I would like to ask (inaudible) whether he could tell us the potential size of acquiring it in terms of size and value. Secondly, you taught us about your risk in terms of innovation and Phase 2 trial duration.

So I would like to have some update on the past method trial, which might slightly disappointing. Four drugs, initially, two which left them - you're left with (inaudible). Do you think that adding financial resources, this drug could be continued and same question for (inaudible), which has been enforced before four years. And also a financial question concerning 2004 forecast, what's the share of - share buyback for 2004?

As far as hyponatremia is concerned, the - an appropriate secretion of anti-diuretic hormones remains a niche. But if you talk about hyponatremia in general, whatever its origin and, in particular, in elderly patients, obviously, the market is much more sizable than what you could expect. But I'm not in a position to give you a precise idea about the size of the market today. But it's probably more significant than expected. As far as (inaudible) is concerned, it has been reviewed by the major trials, but it's not a disappointment for us. We had - we were fortunate enough to have four Phase 2A drugs. And we compare these four drugs at (inaudible). Zenaton (ph) was launched for schizophrenia, especially to combat anti-delusion syndromes. We're trying to determine the best possible dose for the compound. But I'm very sorry. It has not been (inaudible) trial for four years, just three.

Maybe we're not (inaudible) enough. If you hint that we have some financial concern to develop all our compounds and this is precisely the reason why we would like to have this measure with Aventis. The answer is yes. With four billion euro budget, we would have an eloquent budget to develop both Aventis and our own drug, as far as (inaudible) is concerned. And we have already - the report is that ...

[Audio Gap]

... for schizophrenia. The inclusion of patients is something quite uneasy. This is why we give up. It's true that (inaudible) to be with this drug for sleep disorders and you will remember what we already showed after the (inaudible) in apnea, the drug, increases the deep sleep and decreases the so-called light.

As far as 2004 is concerned, the growth of EPS - 15% (ph) for 2004 with $1.25 per euro rate does not take into consideration the significant accretive effect, which we had in 2003. We have a remnant effect of buyback - share buyback products in 2003, 20 million actions (ph) wanted (ph) in euros. And the authorization, which was given to us by the borders (inaudible) was partly (ph) in 2003, we did not buy back any shares at the beginning of the year. And we won't do so before closing on the offer. We didn't take into consideration (inaudible) the EPS growth any significant accretive effect in our compound.

However, these forecasted growth for 2004 is supported by a very strong increase of our research and development investments without any drug divestiture, as we already said.

And last question, I have two questions - Mr. (inaudible), you said, in your presentation, that mature drugs were also considered by you as very valuable. Could you tell us a bit more about their worth in terms of sales? And also the amount of free cash flow that you could retrieve from these mature growth to finance growth. Now, a more fundamental question on research and how have you managed research in the past? But also to emphasize the nature of the risks. (inaudible) told us that he was indeed very fortunate. Well, (inaudible) that has not only the chance, but also talent. So do you really believe that for five or 10 years the development of these compounds might be considered just purely fortuitous and could therefore be questioned in 10 years from now?

Also, some years ago, when we went to (inaudible) with financial analysts, asking the research manager what was the reason of the actual success of development. And asking him who were those who had indeed found. And he was very well - there are three men who actually find something. But more particularly, one. And he is the one whom we really care for. So I'd like to ask you how you assess the risk of research for the future and how you consider managing the combination of those two poles of research that you might be responsible for in the coming months.

We'll be very quick on mature products, which represent 30% and that we have 70% of our drugs that are blockbusters - 33% to be precise. Yes. Thank you very much, (inaudible), for this precision. (inaudible) is very much into figures. Well, these are important drugs for which we devote many efforts. I think that you can probably manage a company with mature products that would decline by 10% per anum. This would be extremely difficult to manage. You might recap part of it, but you have to ensure promotion as well. So it's a matter of will more than a problem of calculation. Now, as to (inaudible) and his chance, the thing that has the best chance, it's not true to say that only a few people are in a position to find something. It's a team. It's a team and very high technology that assumes innovation - innovation in working methods, as well.

And if your question is how do you intend to protect yourself against the possible leave of (inaudible), I think that is really attached to this company in such a way that it's not even worth putting in the question. Or maybe he could answer - he could answer the question.

(inaudible) I have the floor on that with your usual modesty. Well, if we knew how to manage charts (ph), we would systematically succeed. One has to be very humble when being (inaudible) in research. We'll be very careful about the size effect if, indeed, the merger does take place. Research is always conducted with a couple of people. A couple of people who decide on the orientation. Today, we're no longer in the world where we have a man working alone without any links with the outside world. We have a mix of young and old researchers. And among there have been involved in research for more than 30 years. We are always challenged with - by a people who might be slightly less experienced than we are, but who are full with new ideas, which is a source of wealth.

Another point that could be added is that indeed we might have been wrong. That being said, when (inaudible) and myself joined the company seven years ago, we decided on one given orientation, which has been heavily followed all the time. Those who had some concerns with (inaudible), who decided to follow the session - gene therapy or this or that technology. Technology is nothing but a tool. If you decide to indulge in technology, you forget about the true aim of the company, which is drugs. This is how we believe the company should be managed.

I would suggest to bring this discussion to a close because this is a nice word for our future. Thank you very much for your attention. I know that it was a bit long, but I hope that it was worth it. Thank you.