Ipsen: 2013 Half-Year Results and Financial Objectives

Regulatory News:

The Board of Directors of Ipsen (Euronext: IPN; ADR: IPSEY) (Paris:IPN), chaired by Marc de Garidel, met on 29 August 2013 to approve the financial statements for the first half 2013, published today. The interim financial report, with regard to regulated information, is available on the Group´s website, www.ipsen.com, under the Regulated Information tab in the Investor Relations section. The 2013 half year financial statements are subject to a limited review by statutory auditors.

Commenting on the first half 2013 performance, Marc de Garidel, Chairman and Chief Executive Officer of Ipsen, stated: "Our key products, Somatuline® and Dysport®, posted solid growths in the first half 2013, respectively 9.2%1 and 8.4%1. Nevertheless, the first half was marked by a decline in Decapeptyl® sales, stemming partly from price pressure and an increasingly stringent competitive environment and partly from exceptional elements. Ipsen delivered a sound and improving operational performance as a result of good cost control”. Marc de Garidel added: "The Group confirms its long term growth prospects with the acquisition of Syntaxin in the field of toxin engineering and the positive results delivered by our R&D on the Somatuline® CLARINET study”.

1 Sales growth computed year-on-year excluding foreign exchange impacts
2 « Recurring adjusted »: Reconciliations between reported results and recurring adjusted results for H1 2013 and H1 2012 are detailed in appendix 4

Extract of consolidated results

(in millions of euros)

These results were subject to limited review by the auditors

(attributable to shareholders of Ipsen)

(attributable to shareholders of Ipsen)

The 30 June 2012 income statement was restated for purposes of comparison between the two half-year periods, in accordance with provisions related to discontinued operations and changes in accounting methods.
* At current exchange rates
** Active ingredients and raw materials
(1) Before non-recurring elements. See appendix 4

Review of the first half 2013 sales and results

Note: Unless stated otherwise, all variations in sales are stated excluding foreign exchange by restating the H1 2012 figures with the H1 2013 average exchange rate. In compliance with provisions on “discontinued activities” and changes in accounting methods, H1 2012 figures have been restated to provide comparative information between H1 2012 and H1 2013.

The Group’s consolidated sales reached €633.6 million, up 1.2% year-on-year. Sales of Specialty care products amounted to €449.4 million, up 3.0%. Specialty care products accounted for 70.9% of the Group’s consolidated sales, compared to 69.8% the previous year. Sales of Primary care products reached 164.8 million euros, down 4.3% year-on-year.

Specialty Care growth was impacted by an unfavorable comparison base. In the second quarter 2012, the Group posted 19.7% growth at current exchange rates, enhanced by the following effects:

• strong activity on tender offer in Russia on Decapeptyl® and Dysport®;
• stock building in Australia following the agreement signed with Galderma in April 2012;

Specialty Care growth was also impacted by significant events in 2013:

• an exceptional political situation in certain Middle Eastern countries where Ipsen, in the absence of payment guarantees, has stopped supplying Decapeptyl® and to a lesser extent Dysport®, since the end of the first quarter 2013;
• a strained environment in Europe where Decapeptyl® has been negatively impacted by a more frequent use of co-payment (notably in Poland), by a contracting pharmaceutical market in Southern Europe (notably in Spain) and a slowdown in the growth of Eastern European countries;
• the consequences of the ongoing French primary care restructuring plan, mainly impacting Decapeptyl®;
• in China,Decapeptyl® was impacted, by a temporary realignment of inventory in the second quarter 2013 following the Group’s assessment that distributors had overstocked, and by the launch of new local competitors; Moreover, Ipsen was impacted by the recent disruption of the Chinese pharmaceutical market
• the Increlex® shortage in the US in June 2013.

Consequently, Drug sales were up 0.9% year-on-year.

In the first half 2013, sales in the major Western European countries amounted to €256.8 million, down 5.4% year-on-year. The sales growth of specialty care products was more than offset by the consequences of an increasingly competitive environment in Primary care in France and administrative measures in Spain. In Other European countries, sales amounted to €167.7 million in the first half 2013, up 5.4%. Sales growth was mainly driven by the strong performance of Russia where both primary and specialty care (notably Dysport® and Decapeptyl®) performed well despite an unfavorable comparison base resulting from an important tender offer activity in the first half 2012. Sales in North America reached €36.5 million, up 2.3%. In 2012, sales were notably boosted by the recognition of the pediatric use of Increlex® by the Centre for Medicare and Medicaid Services, allowing for a reduced compulsory rebate on the product (from 23% to 17%). Restated from this effect, sales were up 5.5%, driven by the continuous penetration of Somatuline® in acromegaly, where the product exceeded 50% market share1, and by sales of Dysport® in therapeutic, which grew double digit. Dysport® sales were affected by a temporary decline in sales to our partner in North America following its acquisition in 2012. In the Rest of the World, sales amounted to €172.5, up 7.9% year-on-year or 7.0% at current exchange rates. In the first half 2012, sales included the following effects: in Australia, Galderma built a stock following the agreement signed with Ipsen in April 2012; in Vietnam, some orders were brought forward in anticipation of the expiration of primary care import licenses, while in China, the destruction of Etiasa® inventory was observed. Restated from all the aforementioned items, sales grew 13.9% at current exchange rates, to be compared to the 7.0% figure mentioned above.

Other revenues amounted to €30.3 million in the first half 2013, up 6.7% compared to June 2012, when they reached €28.4 million. Growth was mainly driven by the higher royalties paid by the Group partners in aesthetics and to the revenues from the Group´s co-promotion and co-marketing agreements in France.

Consequently, total revenues reached €663.9million in the first half 2013, up 0.9% year-on-year.

The cost of goods sold represented 19.8% of sales compared to 20.5% over the same period in 2012. The favourable mix effects related to the increase in the weight of speciality care products, as well as the productivity efforts implemented by the Group, contributed to offsetting the negative impact of lower Primary Care volumes in France.

R&D expenses increased by €5.7 million compared with June 2012 and represented €124.0 million, or 19.6% of sales, compared with 18.8% of sales in the prior year. Drug-related research and development costs increased 6.5% compared to June 2012. Main research and development projects pursued in the first half 2013 included Dysport® (lower and upper limb spasticity) and the phase II studies of tasquinimod.

Selling, general and administrative expenses amounted to €279.8 million in the first half 2013, representing 44.4% of sales, compared to 43.8% in 2012. The increase is driven by royalties paid to third parties on sales of products marketed by the Group (mainly specialty care products) and by the growth of selling, general and administrative expenses, notably driven by initiatives undertaken to accelerate strategy execution. Moreover, selling expenses (excluding royalties paid) were stable year-on-year, reflecting productivity and selective resource-allocation efforts.

1 US market share of Somatuline® in the sales of somatostatin analogs for acromegaly

In the first half 2013, the Group recorded a €1.3 million profit in the "restructuring costs" line item after reversing a provision in France, notably related to the primary care restructuring plan in France, which more than offset restructuring costs related to reorganization of US Dysport® commercial platform.

In the first half 2013, the Group recognized a non-recurring €11.7 million impairment loss on Increlex®, following the supply interruption effective mid-June in the United States and expected in the third quarter in 2013 in Europe and the Rest of the World. Re-supply is not anticipated before the end of 2013. With this impairment loss, the carrying value of the IGF-1 active ingredient became zero.

Based on the aforementioned items, the operating income in the first half 2013 totaled €121.0 million, or 19.1% of sales, down 3.1% compared to the same period in 2012, when it represented 19.8% of sales.

The Group’s recurring adjusted1 operating income amounted to €132.2 million, or 20.9% of consolidated sales, up 1.2% year-on-year.

At 30 June 2013, the Group’s financial income amounted to €1.1 million, compared with €8.9 million the previous year. The cost of net financial debt represented an income of €6.7 million, mainly stemming from a financial gain on the repayment of Debtor-in-Possession (DIP)-type financing granted by Ipsen to Inspiration Biopharmaceuticals Inc. at the end of 2012 following the sale of its hemophilia assets to Baxter and Cangene. Other financial income and expenses amounted to a €5.6 million charge at 30 June 2013, primarily as a result of a negative €5.0 million foreign exchange impact.

At 30 June 2013, the effective tax rate amounted to 26.0% of profit from continuing operations before tax, compared with an effective tax rate of 25.3% at 30 June 2012. The difference resulted notably from the research tax credit, which despite remaining flat in volume terms from June 2012 to June 2013, increased in relative terms by one percentage point, and a new 3.0% tax implemented in France on dividend payouts that negatively impacted the effective tax rate by 1.6 percentage point. Excluding non-recurring operating, financial and tax items, the Group´s effective tax rate amounted to 25.0% in June 2013, compared with 23.3% in June 2012.

The Group did not record any share of profit or loss from associated companies in the first half 2013.

At 30 June 2013, the result from discontinued operations amounted to a €6.2 million profit, compared to €9.2 million loss at 30 June 2012, and mainly included the negotiated repayment of advisory fees paid by Ipsen during the joint asset-sale process with Inspiration, and the tax impact related to the compensation paid by the Group to the U.S. affiliate which sold its assets.

Consolidated net profit increased 6.4% to €96.5 million (€96.2 million attributable to shareholders of Ipsen S.A.), compared to €90.7 million at 30 June 2012 (€90.4 million attributable to shareholders of Ipsen S.A).

Recurring adjusted1 consolidated net profit at 30 June 2013 amounted to €98.8 million, up 14.3% over the €86.4 million recorded the previous year.

At 30 June 2013, the total of milestone payments received in cash by the Group but not yet recognized in the income statement amounted to €137.3 million compared to €162.7 million collected the previous year.

Net cash flow from operating activities amounted to €54.5 million, compared to €63.2 million generated over the same period in 2012. At 30 June 2013, the Group had closing cash and cash equivalents of €117.6 million, compared to €84.2 million as of 30 June 2012.

Update of 2013 financial objectives

In the first half 2013, our key products, Somatuline® and Dysport®, posted solid growth rates of 9.2% and 8.4%, respectively. Nevertheless, Specialty Care growth was impacted by significant elements that occurred in China and in the Middle East, mentioned above.

Based on those elements, the Group updated its 2013 sales objectives:

Drug sales:

• Specialty Care sales growth of around 3%, excluding unanticipated major deterioration of the Chinese and Middle Eastern markets;
• Primary Care sales decline of around 1%.

The above sales objectives are set year-on-year at constant currency.

1 Before non-recurring items. See appendix 4

Recurring Adjusted Operating Margin:

Moreover, the Group is pursuing the implementation of productivity measures while continuing to invest in its R&D platform and, as a result, confirms its recurring adjusted operating margin1 objective of approximately 16.0% of sales.

All the above objectives are set excluding major negative unforeseeable events, notably significant currency fluctuations in the context of currency depreciation in certain emerging countries.

Media conference call (in French)

Ipsen will host a conference call on Friday 30 August 2013 at 8:30 am (Paris time - GMT+1). Participants in the conference call may connect for the meeting 5-10 minutes prior to its start. No reservations are required to participate. The conference ID is 24065951. The telephone number to call in order to connect to the conference call from France is +33 (0)1 70 70 97 06 and for the other countries it is 44 (0) 1452 560 622. The telephone number to call in order to access a recording of the conference call is from France +33 (0)805 111 337 and for the other countries +44 (0) 1452 55 00 00. The access number is 24065951#. The conference call is available for one week following the meeting.

Meeting, webcast and Conference Call (in English) for the financial community

Ipsen will host an analyst meeting on Friday 30 August 2013 at 2:30 p.m. (Paris time, GMT+1) at its headquarters in Boulogne-Billancourt (France). A web conference (audio and video webcast) and conference call will take place simultaneously. The web conference will be available at www.ipsen.com. Participants in the conference call should dial in approximately 5 to 10 minutes prior to its start. No reservation is required to participate. The conference ID is 935067. No access code is required. Phone numbers to call in order to connect to the conference are: from France and continental +33 (0) 1 70 99 32 12, from UK le +44 (0) 20 7162 0177 and from the United States +1 334 323 6203. A recording will be available shortly after the call. Phone numbers to access the replay of the conference are: from France and continental Europe +33 (0) 1 70 99 32 12, from UK +44 (0) 20 7162 0177 and from the United States +1 334 323 6203 and access code is 935067. This replay will be available for one week following the meeting.

About Ipsen

Ipsen is a global specialty-driven pharmaceutical company with total sales exceeding €1.2 billion in 2012. Ipsen’s ambition is to become a leader in specialty healthcare solutions for targeted debilitating diseases. Its development strategy is supported by 3 franchises: neurology, endocrinology and uro-oncology. Moreover, the Group has an active policy of partnerships. Ipsen´s R&D is focused on its innovative and differentiated technological platforms, peptides and toxins. In 2012, R&D expenditure totalled close to €250 million, representing more than 20% of Group sales. The Group has close to 4,900 employees worldwide. Ipsen’s shares are traded on segment A of Euronext Paris (stock code: IPN, ISIN code: FR0010259150) and eligible to the “Service de Règlement Différé” (“SRD”). The Group is part of the SBF 120 index. Ipsen has implemented a Sponsored Level I American Depositary Receipt (ADR) program, which trade on the over-the-counter market in the United States under the symbol IPSEY. For more information on Ipsen, visit www.ipsen.com.

Forward Looking Statement

The forward-looking statements, objectives and targets contained herein are based on the Group’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect the Group’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today.

Moreover, the targets described in this document were prepared without taking into account external growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by the Group. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising product in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. The Group must face or might face competition from Generics that might translate into a loss of market share.

Furthermore, the Research and Development process involves several stages each of which involves the substantial risk that the Group may fail to achieve its objectives and be forced to abandon its efforts with regards to a product in which it has invested significant sums. Therefore, the Group cannot be certain that favourable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned. The Group also depends on third parties to develop and market some of its products which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to the Group’s activities and financial results. The Group cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of the Group’s partners could generate lower revenues than expected. Such situations could have a negative impact on the Group’s business, financial position or performance.

The Group expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law.

The Group’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers.

APPENDICES

Risk factors

The Group operates in an environment which is undergoing rapid change and exposes its operations to a number of risks, some of which are outside its control. The risks and uncertainties set out below are not exhaustive and the reader is advised to refer to the Group’s 2012 Registration Document available on its website www.ipsen.com.

• The Group is faced with uncertainty in relation to the prices set for all its products, in so far as medication prices have come under severe pressure over the last few years as a result of various factors, including the tendency for governments and payers to reduce prices or reimbursement rates for certain drugs marketed by the Group in the countries in which it operates, or even to remove those drugs from lists of reimbursable drugs.
• The Group depends on third parties to develop and market some of its products, which generates or may generate substantial royalties for the Group, but these third parties could behave in ways that cause damage to the Group’s business. The Group cannot be certain that its partners will fulfill their obligations. It might be unable to obtain any benefit from those agreements. A default by any of the Group’s partners could generate lower revenues than expected. Such situations could have a negative impact on the Group’s business, financial position or performance..
• Actual results may depart significantly from the objectives given that a new product can appear to be promising at a development stage, or after clinical trials, but never be launched on the market, or be launched on the market but fail to sell, notably for regulatory or competitive reasons.
• The Research and Development process typically lasts between eight and twelve years from the date of discovery to a product being brought to market. This process involves several stages; at each stage, there is a substantial risk that the Group could fail to achieve its objectives and be forced to abandon its efforts in respect of products in which it has invested significant amounts. Thus, in order to develop viable products from a commercial point of view, the Group must demonstrate, by means of pre-clinical and clinical trials, that the molecules in question are effective and are not harmful to humans. The Group cannot be certain that favorable results obtained during pre-clinical trials will subsequently be confirmed during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safety and efficacy of the product in question such that the required marketing approvals can be obtained.
• The Group must deal with or may have to deal with competition (i) from generic products, particularly in relation to Group products which are not protected by patents, such as Forlax® and Smecta® (ii), products which, although they are not strictly identical to the Group’s products or which have not demonstrated their bioequivalence, may obtain a marketing authorization for indications similar to those of the Group’s products pursuant to the bibliographic reference regulatory procedure (well established medicinal use) before the patents protecting its products expire. Such a situation could result in the Group losing market share which could affect its current level of growth in sales or profitability.
• Third parties might claim the benefit of intellectual property rights with respect to the Group’s inventions. The Group provides the third parties with which it collaborates (including universities and other public or private entities) with information and data in various forms relating to the research, development, manufacturing and marketing of its products. Despite the precautions taken by the Group with regard to these entities, in particular of a contractual nature, they (or certain of their members or affiliates) could claim ownership of intellectual property rights arising from the trials carried out by their employees or any other intellectual property right relating to the Group’s products or molecules in development.
• The Group’s strategy includes acquiring companies or assets which may enable or facilitate access to new markets, research projects or geographical regions or enable the Group to realize synergies with its existing businesses. Should the growth prospects or earnings potential of such assets as well as valuation assumptions change materially from initial assumptions, the Group might be under the obligation to adjust the values of these assets in its balance sheet, thereby negatively impacting its results and financial situation.
• The marketing of certain products by the Group has been and could be affected by supply shortages and other disruptions. Such difficulties may be of both a regulatory nature (the need to correct certain technical problems in order to bring production sites into compliance with applicable regulations) and a technical nature (difficulties in obtaining supplies of satisfactory quality or difficulties in manufacturing active ingredients or drugs complying with their technical specifications on a sufficiently reliable and uniform basis). This situation may result in inventory shortages and/or in a significant reduction in the sales of one or more products. More specifically, in their US Hopkinton facility, Lonza, our supplier of IGF-1 (Increlex® drug substance), is experiencing manufacturing issues with Increlex®. Lonza works closely with the Food and Drug Administration (FDA) to solve these issues. Ipsen is diligently addressing management of the shortage period to reduce its impact on the patients and their families. The supply interruption occurred in mid-June 2013 in the US and is expected in Q3 2013 in Europe and the rest of the world. The Group has no visibility on the resumption of supply before the end of 2013.
• In certain countries exposed to significant public deficits, and where the Group sells its drugs directly to public hospitals, the Group could face discount or lengthened payment terms or difficulties in recovering its receivables in full. The Group closely monitors the evolution of the situation in Southern Europe where hospital payment terms are especially long. More generally, the Group may also be unable to purchase sufficient credit insurance to protect itself adequately against the risk of payment default from certain customers worldwide. Such situations could negatively impact the Group’s activities, financial situation and results.
• In the normal course of business, the Group is or may be involved in legal or administrative proceedings. Financial claims are or may be brought against the Group in connection with some of these proceedings. Ipsen Pharmaceuticals, Inc. has received an administrative demand from the United States Attorney’s Office for the Northern District of Georgia seeking documents relating to its sales and marketing of Dysport® (abobotulinumtoxinA) for therapeutic use. Ipsen’s policy is to fully comply with all applicable laws, rules and regulations. Ipsen is cooperating with the U.S. Attorney’s Office in responding to the government´s administrative demand.
• The cash pooling arrangements for foreign subsidiaries outside the euro zone expose the Group to financial foreign exchange risk. The variation of these exchange rates may impact significantly the Group’s results.

Major developments in the first half 2013

During the first half 2013, major developments included:

• On January 17, 2013 – Teijin Pharma Limited, the core company of the Teijin Group’s healthcare business, and Ipsen announced the launch of Somatuline® 60/90/120 mg for subcutaneous injection in Japan for the treatment of acromegaly and pituitary gigantism (when response to surgical therapies is not satisfactory or surgical therapies are difficult to perform). In Japan, Teijin Pharma holds the rights to develop and market the drug.
• On January 24, 2013 – Ipsen and Inspiration Biopharmaceuticals Inc. (Inspiration) announced that they entered into an Asset Purchase Agreement (APA) whereby Baxter International (Baxter) agrees to acquire the worldwide rights to OBI-1, a recombinant porcine factor VIII (rpFVIII) in development for congenital hemophilia A with inhibitors and acquired hemophilia A, and Ipsen’s industrial facility in Milford (Boston, MA). The APA was filed on 23 January 2013, with the US Federal Bankruptcy Court in Boston (MA). The sale is a result of joint marketing and sale process pursued by Ipsen and Inspiration shortly after Inspiration filed for protection under Chapter 11 of the U.S. Bankruptcy Code on October 30, 2012. The APA is subject to certain closing conditions, including Bankruptcy Court and regulatory approvals. Ipsen has agreed to extend the DIP to Inspiration for a period of 45 days i.e. for an additional amount of up to c. $5 million.
• On 6 February 2013 – Ipsen and Inspiration Biopharmaceuticals Inc. (Inspiration) announced that they entered into an Asset Purchase Agreement (APA) whereby Cangene Corporation (Cangene) agrees to acquire the worldwide rights to IB1001, a recombinant factor IX (rFIX) for the treatment of hemophilia B. Under the terms of the APA, Cangene has agreed to pay $5.9 million upfront, up to $50 million in potential additional commercial milestones as well net sales payments equivalent to tiered double digit percentage of IB1001 annual net sales. The APA is subject to certain closing conditions including Bankruptcy Court approval.
• On 7 February 2013 – Ipsen and Braintree Laboratories, Inc., a US-based company specializing in the development, manufacturing and marketing of specialty pharmaceuticals announced that Eziclen® / Izinova® (BLI-800) successfully completed its European decentralized registration procedure involving sixteen countries. The product will be indicated in adults for bowel cleansing prior to any procedure requiring a clean bowel (e.g. bowel visualization including bowel endoscopy and radiology or surgical procedure).
• On 20 February 2013 – Ipsen and Inspiration Biopharmaceuticals Inc. (Inspiration) announced the closing of the sale of the proprietary hemophilia B product, IB1001 (recombinant FIX), to Cangene Corporation (Cangene). Ipsen and Inspiration jointly agreed to sell their respective commercialization rights to IB1001 as part of the transaction. Cangene acquired worldwide rights to IB1001, a recombinant factor IX currently under regulatory review in the United States and Europe.
• On 21 March 2013 – Ipsen and Inspiration Biopharmaceuticals Inc. (Inspiration) announced the closing of the sale of its lead hemophilia program, OBI-1 to Baxter International Inc. (Baxter), the global leader in hemophilia. Baxter acquired worldwide rights to OBI-1, a recombinant porcine factor VIII in development for the treatment of congenital hemophilia A with inhibitors and acquired hemophilia A, as well as Ipsen’s manufacturing facility for OBI-1 in Milford, MA. The Ipsen employees working on the development and manufacturing of OBI-1 were offered employment by Baxter. Baxter has agreed to pay $50 million upfront, up to $135 million in potential additional development and sales milestones as well as tiered net sales payments ranging from 12.5% to 17.5% of OBI-1 global net sales. OBI-1 is currently in a pivotal trial for the treatment of individuals with acquired hemophilia A. As Inspiration’s only senior secured creditor and as the owner of non-Inspiration assets that will be included in the sale of both OBI-1 and IB1001, Ipsen will receive at least 60% of the upfront payments. Over and above these upfront amounts, Ipsen will receive 80% of all payments up to a present value of $304 million and 50% of all proceeds thereafter.
• On 9 April 2013 – Ipsen announced that Health Canada had granted a marketing authorization for Dysport® (Botulinum toxin type A for injection) for the temporary improvement in the appearance of moderate to severe frown lines (glabellar lines) in adult patients younger than 65 years of age. Medicis Aesthetics Canada, a division of Valeant Pharmaceuticals, will market Dysport® for use in aesthetic medicine in Canada.
• On 10 April 2013 – PeptiDream Inc., a Tokyo-based pharmaceutical company (PeptiDream), and Ipsen, a global specialty driven pharmaceutical Group, announced that they have entered into a research collaboration and license option agreement to discover, evaluate, potentially develop and launch therapeutic peptides to treat serious medical conditions in areas of therapeutic focus for Ipsen.
• On 24 April 2013 – Upon proposal of the Appointments and Governance Committee, the Board of Directors of Ipsen will propose to the Combined Shareholders’ Meeting to be held on 31 May 2013 the renewal of the terms of office as Directors of Mr. Antoine Flochel and Mr. Gérard Hauser and the appointment as a Director of Mrs. Martha Crawford in replacement of Mr. Klaus-Peter Schwabe who did not request the renewal of his term of office.
• On 25 April 2013 – Ipsen announced that the supplier of Increlex®’s (mecasermin [rDNA origin] Injection) active ingredient, Lonza, was facing manufacturing issues with Increlex® at its Hopkinton site (MA, USA). Lonza has been working closely with the Food and Drug Administration (FDA) to address these issues. Ipsen has been diligently addressing management of the shortage period to reduce its impact on the patients and their families. The supply interruption occurred in mid-June 2013 in the US and in Q3 2013 in Europe and the rest of the world. Re-supply before the end of 2013 is not currently anticipated.
• On 25 April 2013 – Active Biotech and Ipsen announced that the companies have updated the analysis plan for the 10TASQ10 trial, a global Phase III clinical trial evaluating tasquinimod in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have not yet received chemotherapy. The companies now plan to conduct the primary PFS analysis for the 10TASQ10 trial in 2014, at the same time as the first interim overall survival (OS) analysis. The time point for the OS interim analysis will be driven by the number of OS events. The specified number of radiographic progression-free survival (PFS) events for the primary end-point will have been exceeded at the time of interim OS analysis.
• On 14 June 2013 – Ipsen announced that, as part of the accelerated execution of its strategy in the USA, the Group adopted a new organizational model for the distribution of Dysport® in therapeutic indications. With the growing importance of market access and payer driven decisions in healthcare, Ipsen is shifting its business model toward account management in the USA. As such, the Dysport® sales force has been optimized and refocused on key accounts, which will allow us to better serve physicians and patients. The costs linked to this reorganization are not expected to be material for the Group.
• On 17 June 2013 – Ipsen announced the results of an international phase IIIB study, PRIMARYS, assessing an investigational use of Somatuline® Autogel® (lanreotide) 120mg as first line therapy in newly diagnosed acromegaly patients with a macroadenoma. While PRIMARYS did not meet statistical significance with respect to its primary efficacy endpoint, investigators observed clinically relevant tumor volume reductions, in a majority of patients. Data from secondary biomarker endpoints of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were further supportive of these findings. Baseline GH level was the main factor identified as potential predictor for tumor response to primary therapy. Data were presented at the Endocrine Society annual congress (ENDO Congress, San Francisco, USA) on June 16th, 2013. PRIMARYS is the first study of a somatostatin analogue in such a large and homogeneous population (90 treatment-naïve acromegalic patients with macroadenoma) to evaluate tumor volume reduction as the primary endpoint using Magnetic Resonance Imaging (MRI) with a very robust and unique methodology for central assessment.

After 30 June 2013, major developments included:

• On 11 July 2013 – Ipsen announced results from the primary endpoint of the CLARINET study, assessing the effect of Somatuline® Autogel® 120 mg on tumor progression-free survival in patients with GEP-NETs. Treatment with Somatuline® Autogel® 120mg was found to be statistically significantly superior to placebo in extending time to either disease progression or death. The safety profile observed in the study is consistent with the known safety profile of Somatuline®. Comprehensive results from this study will be disclosed at the annual meeting of the European Society of Medical Oncology (ESMO) (Sept. 27 – Oct. 1, 2013). CLARINET provides medically important results as it is the first large scale placebo-controlled randomized study to demonstrate the antitumoral activity of a somatostatin analog in non-functioning GEP-NETs.
• On 15 July 2013 – Ipsen announced the closing of the acquisition of Syntaxin, a UK-based private life sciences company specialized in botulinum toxin engineering. Under the terms of the agreement, Ipsen will pay €28 million upfront, as well as further contingent payments that could reach €130 million or more depending on the achievement of development and commercial milestones. Furthermore, Syntaxin’s shareholders will receive the greater part of additional downstream payments related to the company’s most advanced asset, currently in Phase II clinical trials. The transaction fits into Ipsen’s strategy to reinforce its core technological platforms, peptides and toxins. Syntaxin has a wealth of experience in botulinum toxin biology, supported by an extensive patent portfolio – with 75 granted patents and over 130 patents pending. Syntaxin and Ipsen started collaborating in 2010. In 2011, they signed a global strategic partnership to explore the discovery and development of new compounds in the field of recombinant botulinum toxins. Syntaxin’s team has used its extensive expertise in the discovery of new therapeutic candidates while Ipsen applied its skills to pharmacological, preclinical and clinical assessment of the compounds. Prior to the transaction, Ipsen owned c.10% of Syntaxin’s capital on a fully diluted basis.
• On 15 July 2013 – Ipsen announced that it had initiated a research and development collaboration on novel engineered botulinum toxins with Harvard Medical School (Harvard). Under the terms of the agreement, Ipsen will fund Harvard research for at least three years with the aim to discover, evaluate and develop novel engineered recombinant botulinum toxins for the treatment of serious neurologic diseases. The collaboration will combine Harvard’s discovery platform and botulinum toxins engineering expertise with Ipsen’s know-how in drug discovery and pharmaceutical R&D. Ipsen will have exclusive worldwide rights on any candidate recombinant toxin stemming from the collaboration. Ipsen will be responsible for the development and marketing of the new toxins and will make associated upfront, milestones and royalty payments to Harvard.
• On 29 August 2013 – Ipsen announced the departure of Eric Drapé, Executive Vice-President, Technical Operations. Christel Bories, Deputy CEO, will take over his responsibilities on an interim basis.
• On 29 August 2013 – Ipsen and Allergan have signed an agreement to settle their dispute on patents for the therapeutic use of botulinum toxin in urology indications. This agreement will not impact the Group’s treasury.

Government measures

In the current context of financial and economic crisis, the governments of many countries in which the Group operates continue to introduce new measures to reduce public health expenses, some of which are affecting the Group sales and profitability in 2013. In addition, certain measures introduced in 2012 have continued to affect the Group´s accounts year-on-year.

Measures impacting 2013

In the Major Western European countries:

• In France, Tanakan® was delisted on 1st March 2012. An additional tax on promotional expenses of 0.6% was also introduced. Moreover, sales of Nisis®/Nisisco® and Forlax® were negatively impacted by a step-up in the regulation known as “Tiers-payant” in July 2012, whereby the patient must pay upfront for a branded drug at the pharmacy – when genericized – and is reimbursed only later on. Finally, a 5.5% price decrease on NutropinAq® was imposed by health authorities starting in June 20

  ---

  ---