Triptorelin acetate

2022 total sales up by 8.5% at CER1 (14.4% as reported) with growth platforms’2 sales increasing by 20.9%1 and Somatuline® (lanreotide) sales declining by 5.6%1 2022 core operating margin of 36.9%, broadly in line with 2021; IFRS operating margin of 24.1%, down by 7.1% points, reflecting the impact of the acquisition of Epizyme and impairment losses on intangible assets Successful delivery of strategy, driving strong growth, advancement of the pipeline and further external-innovation transactions, including the acquisition of Epizyme and the divestment of Consumer HealthCare 2023 financial guidance: total-sales growth greater than 4.0% at CER1; core operating margin around 30% of total sales Paris (France), 9 February 2023 Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-driven biopharmaceutical company, presents today its financial results for the year and the fourth quarter of 2022. Extract of consolidated results for FY 2022 and FY 20213: FY 2022 FY 2021 % change €m €m Actual CER1 Total Sales 3,025.0 2,643.3 14.4% 8.5% Core Operating Income 1,115.4 983.1 13.5% Core operating margin 36.9% 37.2% -0.3% pts Core Consolidated Net Profit 872.4 740.1 17.9% Core earnings per share (fully diluted) 10.51 8.88 18.4% IFRS Operating Income 729.9 824.7 -11.5% IFRS operating margin 24.1% 31.2% -7.1% pts IFRS Consolidated Net Profit 647.5 646.7 0.1% IFRS earnings per share (fully diluted) 7.81 7.76 0.6% Dividend per share €1.204 €1.20 — Free Cash Flow 817.2 780.7 4.7% Net cash5 398.8 28.06 n/a David Loew, Chief Executive Officer, commented: “2022 was a year of strong results and clear progress on our strategic roadmap. Improving execution supported another excellent sales performance from our growth platforms in Oncology and Neuroscience. I was particularly pleased with the progress of the pipeline, including the recent clinical-trial results for Onivyde, which could significantly benefit patients with pancreatic cancer. We have also been replenishing the pipeline at pace through the acquisition of Epizyme in Oncology and, more recently, the announcement of Albireo in Rare Disease. Our external-innovation strategy, underpinned by a strong balance sheet and increasing cash generation, is expanding the number of potential medicines we have across our three therapy areas, and we have the ambition to enlarge the pipeline further. With the Company fully focused on Specialty Care, the outlook is promising, reflecting our commitment to bringing more medicines to patients and ensuring the sustainable growth of Ipsen.” Delivering on strategy Ipsen delivered successfully on the second year of the implementation of its strategy: Focus. Together. For patients and society. The divestment of the Consumer HealthCare (CHC) business in 2022 was a major step forward towards building a more focused Ipsen, centering on Specialty Care. The growth platforms produced a double-digit performance, including Dysport, which grew by 29.4%%7 and Cabometyx, up by 23.9%7. There were also favorable developments from the existing pipeline, including positive results from the Phase III trial of the Onivyde-based regimen in pancreatic cancer, as well as the initiation of new trials, including a Phase II trial of elafibranor in rare liver disease. It was also a particularly strong period of replenishment of the pipeline, founded on the strong execution of Ipsen’s external-innovation model. Through a combination of in-licensing and acquisitions, the Company has added 20 new assets to the pipeline in the last two years across the three strategic therapy areas of Oncology, Rare Disease and Neuroscience. In 2022, Ipsen strengthened its position in Oncology by acquiring Epizyme, a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies against novel epigenetic targets for cancer patients. More recently, Ipsen announced its intention to acquire Albireo8, a leading innovator in bile-acid modulators to treat pediatric and adult cholestatic liver diseases. This anticipated acquisition is designed to enrich Ipsen’s Rare Disease portfolio and pipeline. Finally, the Company continued to drive benefits from its global efficiencies program, yielding savings across the entire cost base, which enabled significant further investment in Ipsen’s priorities for growth. Full-year 2023 guidance Ipsen has set the following financial guidance for FY 2023, assuming the completion of the planned acquisition of Albireo, expected to close in the first quarter of the year: Total-sales growth greater than 4.0%, at constant currency. Based on the average level of exchange rates in January 2023, an anticipated adverse impact on total sales of around 2% from currencies Core operating margin around 30% of total sales, excluding any potential impact of incremental investments from future external-innovation transactions Ipsen intends to provide a mid-term outlook before the end of 2023, following the anticipated completion of the acquisition of Albireo8, as well as a number of pipeline milestones. Business development update In January 2023, Ipsen and Albireo announced that they had entered into a definitive merger agreement under which Ipsen will acquire Albireo, a leading innovator in bile-acid modulators to treat pediatric and adult cholestatic liver diseases. The anticipated acquisition will enrich Ipsen’s Rare Disease portfolio and pipeline. The lead medicine in Albireo’s pipeline is Bylvay® (odevixibat), the first-approved treatment in progressive familial intrahepatic cholestasis in the U.S. and E.U., with potential in other rare diseases. The transaction is anticipated to close in the first quarter of 2023. Pipeline update In November 2022, Ipsen announced that the NAPOLI 3 Phase III trial of Onivyde plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX regimen), compared to nab-paclitaxel plus gemcitabine in previously untreated patients with metastatic pancreatic ductal adenocarcinoma, met its primary endpoint, demonstrating a clinically meaningful and statistically significant improvement in overall survival. The full trial results were presented in January 2023 at the American Clinical Society of Oncology Gastrointestinal Cancers Symposium in San Francisco, U.S. In December 2022, Ipsen announced that the CONTACT-01 Phase III trial of Cabometyx, in combination with atezolizumab, compared to docetaxel in patients with unmutated metastatic non-small cell lung cancer who experienced disease progression on or after treatment with an immune checkpoint inhibitor and platinum-containing chemotherapy, did not meet its primary endpoint of an improvement in overall survival. In December 2022, the U.S. FDA issued a Complete Response Letter (CRL) regarding the New Drug Application for palovarotene, an investigational treatment for the reduction of new abnormal bone formation (heterotopic ossification) in people living with fibrodysplasia ossificans progressiva. The CRL was related to the regulatory agency’s previous request for additional information on palovarotene clinical-trial data communicated to Ipsen in October 2022, which was not a request for additional efficacy or safety data beyond existing studies. Ipsen anticipates responding to the request in the first quarter of 2023, with an expected six-month U.S. FDA review cycle. In January 2023, Ipsen received a negative opinion from the CHMP9 for palovarotene in the same indication. The Company will request a re-examination of the opinion, based on scientific data available from the existing palovarotene clinical-trial program. Environment, Social and Governance: Generation Ipsen Ipsen is committed to science-based reductions in greenhouse-gas emissions and its near-term climate targets were independently validated by the Science Based Target initiative in 2022. Ipsen now uses 100% green electricity for all operations in the U.K., the Republic of Ireland and France. This increased the Company’s use of electricity from renewable sources to 90%, in line with a commitment to 100% renewable-electricity use by 2025. Another action was a further decarbonizing of Ipsen’s processes that have traditionally used fossil fuels to produce heat and steam for the manufacturing process, while a new Fleet For Future program is focused on the transitioning of at least 30% of Ipsen’s vehicle fleet to battery-electric vehicles by 2025. The Company is focused on patients’ access to medicines, including the provision in 2022 of humanitarian relief in response to the crisis in Ukraine via patient support, medicine donations and funding to the Red Cross and Tulipe charities. The partnership with Access Accelerated, a not-for-profit collective that works in communities that lack sufficient access to healthcare to address non-communicable diseases, also continued to thrive. Finally, Fondation Ipsen, under the aegis of the Fondation de France, again reached millions of people impacted by rare diseases, helping to improve lives across around 100 countries. Consolidated financial statements The Board of Directors approved the consolidated financial statements on 8 February 2023. The consolidated financial statements have been audited and the Statutory Auditors’ report is in the process of being published. Ipsen’s comprehensive audited financial statements will be available in due course on ipsen.com (regulated-information section). Conference call A conference call and webcast for investors and analysts will begin today at 1.45pm, Paris time. Participants can access the call and its details by registering here; webcast details can be found here. Calendar Ipsen intends to publish its first-quarter sales update on 27 April 2023. Notes All financial figures are in € millions (€m). The performance shown in this announcement covers the twelve-month period to 31 December 2022 (the year or FY 2022) and the three-month period to 31 December 2022 (the fourth quarter or Q4 2022), compared to twelve-month period to 31 December 2021 (FY 2021) and the three-month period to 31 December 2021 (Q4 2021), respectively, unless stated otherwise. Commentary is based on the performance in FY 2022, unless stated otherwise. The performance of the CHC business, divested in July 2022, has been excluded from all commentary and comparisons to prior performance. Ipsen Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With total sales of €3.0bn in FY 2022, Ipsen sells medicines in over 100 countries. Alongside its external-innovation strategy, the Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has around 5,000 colleagues worldwide and is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com. Contacts Investors Craig Marks Vice President, Investor Relations +44 7584 349 193 Adrien Dupin de Saint-Cyr Investor Relations Manager +33 6 64 26 17 49 Media Amy Wolf Vice President and Head of Corporate Brand Strategy and Communications +41 79 576 07 23 Ioana Piscociu Senior Manager, Global Media Relations +33 6 69 09 12 96 Total sales by therapy area and medicine FY 2022 FY 2022 FY 2021 % change Q4 2022 Q4 2021 % change €m €m Actual CER1 €m €m Actual CER10 Oncology 2,379.5 2,153.5 10.5% 4.7% 612.3 588.1 4.1% -1.1% Somatuline 1,218.0 1,202.7 1.3% -5.6% 306.1 328.3 -6.8% -13.3% Decapeptyl 529.7 459.6 15.3% 12.4% 133.7 127.0 5.3% 3.9% Cabometyx 448.7 354.6 26.6% 23.9% 121.0 96.0 26.1% 23.1% Onivyde 162.4 127.4 27.4% 14.1% 40.4 34.4 17.3% 5.9% Tazverik® 12.7 0.0 n/a n/a 9.9 0.0 n/a n/a Other Oncology 8.0 9.1 -12.2% -12.3% 1.1 2.4 -52.0% -51.6% Neuroscience 604.4 440.7 37.2% 29.7% 196.7 131.1 50.1% 40.6% Dysport 593.6 434.6 36.6% 29.4% 193.2 129.3 49.4% 40.4% Other Neuroscience 10.8 6.1 78.8% 52.1% 3.5 1.7 99.3% 59.7% Rare Diseases 41.1 49.1 -16.4% -18.3% 7.6 11.8 -36.1% -36.1% NutropinAq® 27.2 32.0 -15.1% -15.3% 6.4 7.5 -14.8% -14.8% Increlex® 13.9 17.1 -18.7% -23.8% 1.2 4.3 -73.1% -73.7% Total Sales 3,025.0 2,643.3 14.4% 8.5% 816.4 731.0 11.7% 5.8% Commentary is based on the performance in FY 2022, unless stated otherwise. Somatuline: in North America, sales fell by 7.5%10, despite continued demand growth, with impacts from increased competition and adverse U.S. pricing, driven by an increased level of commercial rebates and unfavorable movements in channel mix, as well as lower wholesaler inventories. In the fourth quarter, Somatuline sales in North America declined by 17.6%10, augmented by the difference in year-on-year levels of inventories in the U.S. In Europe, sales declined by 11.6%10, reflecting the larger effects of the launches of generic lanreotide in more markets, including Germany, France, Spain and Italy. Sales in the Rest of the World grew by 36.7%10, a result of strong performances in several geographies, including the Middle East, Japan, Russia, and Brazil. Dysport: The performance was driven by growth in the aesthetics market, including increased sales to Ipsen’s partner, Galderma, in North America, Brazil and Australia, and strong demand in most therapeutics markets. Stronger growth in the second half of the year reflected a recent manufacturing-capacity increase that benefitted supply to meet aesthetics-market demand. Decapeptyl: the performance was mainly driven by continued market-share gains in Europe, primarily in France, the U.K. and Italy, along with higher volumes in the Rest of the World. In China, sales continued to grow, despite the impact of the ongoing effects of the COVID-19 pandemic. Reduced growth in the fourth quarter reflected a particular impact from the response to the COVID-19 pandemic in China, as well as the phasing of various shipments. Cabometyx: the performance reflected strong volume uptakes in renal cell carcinoma across most geographies, mainly as a second-line monotherapy and, more recently, as a first-line therapy in combination with nivolumab. Onivyde: sales growth was primarily driven by a strong performance in the U.S., as well as increased sales to Ipsen’s ex-U.S. partner. Tazverik: sales in the U.S. were consolidated for the four months from 1 September 2022. Total sales by geographical area FY 2022 FY 2021 % change Q4 2022 Q4 2021 % change €m €m Actual CER11 €m €m Actual CER11 North America 1,032.1 916.3 12.6% 0.4% 272.9 266.5 2.4% -8.7% Europe12 1,237.3 1,205.5 2.6% 2.4% 312.6 318.3 -1.8% -1.4% Rest of the World 755.6 521.4 44.9% 36.7% 231.0 146.2 57.9% 47.4% Total Sales 3,025.0 2,643.3 14.4% 8.5% 816.4 731.0 11.7% 5.8% Commentary is based on the performance in FY 2022. North America: sales growth of 0.4%11 was driven by a continued strong performance from Dysport in the therapeutics market and, in the aesthetics market, through Galderma, and from Onivyde, offset by a Somatuline sales decline of 7.5%11. Europe: sales growth of 2.4%11 mainly reflected strong Cabometyx performances in France, Spain, Poland and Germany, Decapeptyl’s continued market-share uptakes and Onivyde’s performance through Ipsen’s partner. Dysport sales grew by 9.8%11, a result of volume uptakes in the therapeutics market. Following the advance of generic lanreotide in a larger number of European markets, Somatuline sales declined by 11.6%11. Rest of the World: sales growth of 36.7%11 was driven by a solid volume performance in both Oncology and Neuroscience. In Oncology, the increase in Decapeptyl sales reflected volume growth in China, with continued share gains in several markets. The strong performance of Cabometyx was also a result of market-share gains across a number of geographies, including Brazil, Taiwan and the Middle East. The performance also reflected strong Somatuline sales, including in the Middle East, Japan and Brazil. In Neuroscience, the strong growth of Dysport sales was a result of volume uptakes in aesthetics markets, primarily in Latin America, Australia and the Middle East, as well as solid performances in therapeutics markets. Comparison of core consolidated income statement In accordance with IFRS 5, FY 2022 consolidated net profit and free cash flow resulting from the CHC business have been reclassified in separate line items: ‘Net profit/(loss) from discontinued operations’ in the profit and loss account and ‘Change in net cash/(debt) from discontinued operations’ in the cash-flow statement. The comparative figures for the prior year have been restated accordingly. FY 2022 opening net cash €28.0m, versus FY 2021 closing net debt of €126.4m, reflected the reclassification of the contingent liabilities (earnouts and CVRs13), previously part of the definition of net debt. In the profit and loss account, the change in earnouts related to the probability of success and currency effects, previously impacting the financial results, was recognized in non-core operating income and expenses. The effect of unwinding is still presented in the financial results. FY 2021 was restated for these impacts. Epizyme was fully consolidated from 1 September 2022. Core financial measures are performance indicators. A reconciliation between these indicators and IFRS aggregates is presented in Appendix 4, ‘Bridges from IFRS consolidated net profit to core consolidated net profit’. FY 2022 FY 2021 % change €m % of total sales €m % of total sales Total Sales 3,025.0 100% 2,643.3 100% 14.4% Other revenue 131.5 4.3% 105.4 4.0% 24.7% Total Revenue 3,156.4 104.3% 2,748.6 104.0% 14.8% Cost of goods sold (527.7) (17.4)% (438.6) (16.6)% 20.3% Selling expenses (833.4) (27.6)% (728.1) (27.5)% 14.5% Research and development expenses (445.3) (14.7)% (424.4) (16.1)% 4.9% General and administrative expenses (205.8) (6.8)% (188.2) (7.1)% 9.3% Other core operating income 0.4 — 13.9 0.5% n/a Other core operating expenses (29.2) (1.0)% (0.1) — n/a Core Operating Income 1,115.4 36.9% 983.1 37.2% 13.5% Net financing costs (18.5) (0.6)% (21.8) (0.8)% (15.2)% Core other financial income and expense (13.4) (0.4)% (14.5) (0.5)% (7.2)% Core income taxes (210.8) (7.0)% (207.1) (7.8)% 1.8% Share of net profit/(loss) from equity-accounted companies (0.3) — 0.4 — n/a Core Consolidated Net Profit 872.4 28.8% 740.1 28.0% 17.9% - Attributable to shareholders of Ipsen S.A. 873.5 28.9% 740.0 28.0% 18.1% - Attributable to non-controlling interests (1.3) — 0.1 — n/a Core EPS14 fully diluted: attributable to Ipsen S.A. shareholders €10.51 €8.88 18.4% Reconciliation from core consolidated net profit to IFRS consolidated net profit Total sales Total sales grew in 2022 by 8.5% at CER15, or 14.4% as reported, which included a positive impact from currencies of 5.9%. Other revenue Other revenue totaled €131.5m, an increase of 24.7%, reflecting the growth in royalties received from partners, primarily Galderma for Dysport. Cost of goods sold Cost of goods sold of €527.7m represented 17.4% of total sales, an increase as a percentage of total sales of 0.8 percentage points (FY 2021: €438.6m, or 16.6%), mainly due to an unfavorable mix impact and an increase in royalties paid to Ipsen’s Cabometyx partner. Selling expenses Selling expenses increased by 14.5% to €833.4m, driven by the integration of Epizyme, commercial efforts deployed to support sales growth and the impact of foreign exchange, partly offset by the Company’s efficiency program. Selling expenses represented 27.6% of total sales, in line with the prior year (FY 2021: 27.5%). Research and development expenses Research and development expenses totaled €445.3m, representing growth of 4.9%, with reduced lifecycle-management investment in Oncology for Onivyde and Cabometyx offset by the impact of the acquisition of Epizyme and increased investment in Neuroscience, notably for next-generation neurotoxins, and in Rare Disease for elafibranor. Research and development expenses represented 14.7% of total sales, a decline of 1.3 percentage points versus the prior year (FY 2021: 16.1%). General and administrative expenses General and administrative expenses increased by 9.3% to €205.8m. The ratio to total sales declined to 6.8% (FY 2021: 7.1%). Other core operating income and expenses Other core operating income and expenses amounted to an expense of €28.8m (FY 2021: an income of €13.8m), reflecting the impact of Ipsen’s currency-hedging policy. Core operating income Core operating income amounted to €1,115.4m, growing by 13.5%, with a core operating margin at 36.9% of total sales, a decline of 0.3 percentage points, reflecting the dilutive impact from the acquisition of Epizyme. Core net financing costs and other financial income and expense Ipsen incurred net financial expenses of €31.9m (FY 2021: €36.3m). Net financing costs declined by €3.3m to €18.5m, driven by higher interest rates on investment income. Other financial income and expense declined by €1.1m to €13.4m, mainly reflecting reduced foreign-exchange impacts on non-commercial transactions. Core income taxes Core income tax expense of €210.8m reflected a higher profit before tax, combined with a lower core effective tax rate of 19.5% (FY 2021: 21.9%), mainly impacted by the reclassification of Orphan Drug tax credits from research and development expenses to income taxes. Core consolidated net profit Core consolidated net profit increased by 17.9% to €872.4m (FY 2021: €740.1m). Core EPS Fully-diluted core EPS came to €10.51, representing growth of 18.4% (FY 2021: €8.88). From core financial measures to IFRS reported figures FY 2022 FY 2021 €m €m Core Consolidated Net Profit 872.4 740.1 Amortization of intangible assets (excluding software) (78.7) (59.6) Other operating income and expenses (105.4) (36.3) Restructuring costs (20.2) (14.6) Impairment losses (86.1) (6.5) Others 65.5 23.6 IFRS Consolidated Net Profit 647.5 646.7 IFRS EPS Fully Diluted - Attributable To Ipsen S.A. Shareholders €7.81 €7.76 Amortization of intangible assets (excluding software) Amortization of intangible assets (excluding software) amounted to €103.6m before tax (FY 2021: €79.4m). The variation mainly related to the amortization of intangible assets for Cabometyx. Other operating income and expenses Other non-core operating expenses of €140.6m before tax mainly related to the acquisition of Epizyme and transaction costs, Ipsen’s transformation programs, the divestment of the CHC business, the discontinuation of clinical trials and the change in Onivyde earnouts following clinical-trial results for new indications. Other non-core operating expenses in FY 2021 totaled €50.3m before tax, mainly related to costs arising from Ipsen’s transformation programs. Restructuring costs Restructuring costs came to €26.9m before tax, mainly related to Epizyme-integration costs. Restructuring costs in 2021 amounted to €19.6m before tax, reflecting transformation projects in France and the U.S. Impairment losses Ipsen recognized an impairment losses on intangible assets of €114.3m before tax, including €55.1m for palovarotene, following the issuance of a Complete Response Letter by the U.S. FDA and the negative opinion from the European Medicines Agency's committee responsible for human medicines, and €59.3m on Neuroscience and Oncology intangible assets, following unfavorable clinical-trial results. In FY 2021, the Company recognized an impairment loss on intangible assets of €9.1m before tax, following an unfavorable clinical-trial result. Others Financial income and expenses and income taxes amounted to an income of €11.3m (FY 2021: €8.1m). Net profit from discontinued operations of €55.4m corresponded to the gain on the CHC divestiture and the contribution of the CHC business in the first half of 2022. IFRS financial measures Operating income Operating profit amounted to €729.9m, declining by 11.5% (FY 2021: €824.7m), mainly due the recognition of impairment losses in FY 2022. Consolidated net profit Consolidated net profit was €647.5m, in line with last year (2021: €646.7m). EPS Fully-diluted EPS amounted to €7.81 per share, in line with the prior year (FY 2021: €7.76 per share). Net cash flow and financing FY 2022 opening net cash amounted to €28.0m versus FY 2021 closing net debt of €126.4m, reflecting the reclassification of contingent liabilities (earnouts and CVRs), previously part of the definition of net debt. FY 2022 FY 2021 €m €m Opening Net Cash/(Debt) Including Contingent Liabilities (Earnouts & CVRs) (126.4) (525.3) Contingent liabilities (earnouts & CVRs) 154.4 137.2 Opening Net Cash/(Debt) 28.0 (388.0) Ipsen had a net cash increase of €370.8m, bringing closing net cash to €398.8m. FY 2022 FY 2021 €m €m Opening Net Cash/(Debt) 28.0 (388.0) Core Operating Income 1,115.4 983.1 Non-cash items 105.1 143.4 Change in operating working capital requirement (77.6) 10.7 (Increase)/decrease in other working capital requirement 77.4 (25.3) Net capital expenditures (excluding milestones paid) (140.6) (109.7) Dividends received from entities accounted for using the equity method — — Operating Cash Flow 1,079.6 1,002.3 Other non-core operating income and expenses and restructuring costs (63.3) (48.7) Financial income (23.6) (28.9) Current income tax (167.2) (144.8) Other operating cash flow (8.3) 0.9 Free Cash Flow 817.2 780.7 Distributions paid (100.2) (83.1) Net investments (business development and milestones) (564.5) (240.4) Share buyback (11.3) (36.7) FX on net indebtedness (20.4) (30.3) Change in cash/(debt) from discontinued activities 249.0 25.7 Other 1.0 — Shareholders Return And External Growth Operations (446.4) (364.7) CHANGE IN NET CASH/(DEBT) 370.8 416.0 Closing Net Cash/(Debt) 398.8 28.0 Operating cash flow Operating cash flow totaled €1,079.6m, an increase of €77.3m (+7.7%), driven by higher core operating income (an increase of €132.3m) and a better other working-capital-requirement change (€102.7m, reflecting the reimbursement in FY 2022 of tax refunds, combined with a variable-compensation increase), partly offset by higher operating working-capital requirements (€88.3m mainly from higher trade receivables), higher capital expenditures (€30.9m, including projects to increase capacity and efficiency at industrial sites, as well as IT and digital projects), and lower other non-cash items, impacted by transformation projects, mostly in the U.S., and the termination of R&D trials. Free cash flow Free cash flow grew by €36.5m to €817.2m (FY 2021: €780.7m), reflecting higher operating cash flow, partly offset by an increase in income tax and other non-core expenses and restructuring costs. Shareholders’ return and external growth operations The distribution payout to Ipsen S.A. shareholders amounted to €100.2m in FY 2022, corresponding to a 2021 dividend per share of €1.20, paid in 2022 (FY 2021: €83.1m, for a 2020 dividend of €1.00 per share, paid in 2021). Net investments of €564.5m were mainly related to the acquisition of Epizyme for €400.3m and the in-licensing agreement with Marengo Therapeutics for €44.9m, as well as additional Cabometyx commercial and regulatory milestones paid to Exelixis for €122.8m and a development milestone for fidrisertib paid to Blueprint Medicines for €28.5m. Net investments in FY 2021 amounted to €240.4m, mainly driven by investments in external innovation, including the upfront payment related to the licensing agreement for elafibranor and the purchase of shares for a total of €148.0m, and Cabometyx commercial milestones of €50.7m paid to Exelixis. Foreign exchange on net indebtedness adversely impacted net debt, mainly due to a higher U.S. dollar versus Euro. Reconciliation of cash and cash equivalents and net cash FY 2022 FY 2021 €m €m Current Financial Assets (Derivative Instruments On Financial Operations) 2.5 0.6 Closing Cash And Cash Equivalents 1,165.5 809.1 Non-current loans (581.8) (562.8) Other non-current financial liabilities (excluding derivative instruments)16 (85.1) (100.0) Non-Current Financial Liabilities (666.9) (662.8) Credit lines and bank loans — — Other current financial liabilities (excluding derivative instruments)16 (102.3) (118.9) Current Financial Liabilities (102.3) (118.9) Debt (769.2) (781.8) Net Cash/(Debt)17 398.8 28.0 Analysis of cash On 16 June 2016, Ipsen S.A. issued €300m in unsecured, seven-year public bonds. On 24 May 2019, Ipsen S.A. signed an initial five-year Revolving Credit Facility (RCF) of €1,500m, which has been extended twice to May 2026. On 23 July 2019, Ipsen S.A. issued $300m through a U.S. Private Placement (USPP) in two tranches of 7 and 10‑year maturities. Ipsen must comply with a net debt / EBITDA covenant to remain below 3.5 times at each financial closing in both the RCF and the USPP. Ipsen complied with its covenant ratio for the RCF and the USPP. The RCF also includes specific indicators linked to Corporate Social Responsibility, assessed annually. On 31 December 2022, the RCF was fully undrawn and Ipsen S.A.’s program of emission of NEU CP – Negotiable EUropean Commercial Paper of €600m, was drawn for €65m. Appendix 1: consolidated income statement FY 2022 FY 202118 €m €m Total Sales 3,025.0 2,643.3 Other revenue 131.5 105.4 Total Revenue 3,156.4 2,748.6 Cost of goods sold (527.7) (438.6) Selling expenses (833.4) (728.1) Research and development expenses (445.3) (424.4) General and administrative expenses (205.8) (188.2) Other operating income 32.1 52.5 Other operating expenses (305.1) (168.4) Restructuring costs (26.9) (19.6) Impairment losses (114.3) (9.1) Operating Income 729.9 824.7 Net financing costs (18.5) (21.8) Other financial income and expenses (5.5) (13.8) Income taxes (112.3) (158.3) Share of net profit/(loss) from equity-accounted companies (1.5) 0.4 Net Profit/(Loss) From Continuing Operations 592.1 631.2 Net profit (loss) from discontinued operations 55.4 15.5 Consolidated Net Profit/(Loss) 647.5 646.7 - Attributable to shareholders of Ipsen S.A. 648.6 646.6 - Attributable to non-controlling interests (1.1) 0.1 Basic earnings per share, continuing operations (in euros) €7.20 €7.64 Diluted earnings per share, continuing operations (in euros) €7.14 €7.57 Basic earnings per share, discontinued operations (in euros) €0.67 €0.19 Diluted earnings per share, discontinued operations (in euros) €0.66 €0.19 Basic Earnings Per Share (In Euros) €7.87 €7.82 Diluted Earnings Per Share (In Euros) €7.81 €7.76 Appendix 2: consolidated balance sheet before allocation of net profit 31 December 2022 31 December 202119 €m €m ASSETS Goodwill 579.9 623.2 Other intangible assets 1,585.4 1,370.0 Property, plant & equipment 581.4 647.5 Equity investments 109.8 106.9 Investments in equity-accounted companies 26.4 26.2 Non-current financial assets 0.1 0.1 Deferred tax assets 321.1 258.7 Other non-current assets 6.1 4.3 Total Non-Current Assets 3,210.3 3,036.7 Inventories 284.1 219.4 Trade receivables 632.5 564.3 Current tax assets 41.2 122.8 Current financial assets 31.0 11.7 Other current assets 239.5 221.0 Cash and cash equivalents 1,169.3 814.7 Total Current Assets 2,397.6 1,953.8 TOTAL ASSETS 5,607.9 4,990.5 EQUITY AND LIABILITIES Share capital 83.8 83.8 Additional paid-in capital and consolidated reserves 2,547.4 1,967.7 Net profit (loss) for the period 648.6 646.6 Foreign exchange differences 57.4 37.2 Equity Attributable To Ipsen S.A. Shareholders 3,337.3 2,735.2 Equity attributable to non-controlling interests (0.6) 2.5 Total Shareholders' Equity 3,336.7 2,737.7 Retirement benefit obligation 18.7 40.7 Non-current provisions 68.5 64.0 Other non-current financial liabilities 667.0 662.9 Deferred tax liabilities 77.9 101.8 Other non-current liabilities 103.7 155.1 Total Non-Current Liabilities 935.7 1,024.4 Current provisions 55.6 41.6 Current financial liabilities 113.8 129.7 Trade payables 647.1 594.7 Current tax liabilities 11.8 10.0 Other current liabilities 503.3 446.8 Bank overdrafts 3.8 5.5 Total Current Liabilities 1,335.4 1,228.4 TOTAL EQUITY & LIABILITIES 5,607.9 4,990.5 Appendix 3.1: consolidated statement of cash flow FY 2022 FY 202120 €m €m Consolidated Net Profit 647.5 646.7 Share of profit/(loss) from equity-accounted companies 1.2 (0.4) Net profit from discontinued operations (55.4) (15.5) Net Profit/(Loss) Before Share From Equity-Accounted Companies 593.4 630.8 Non-cash and non-operating items: - Depreciation, amortization, impairment losses and provisions 336.5 246.4 - Change in fair value of financial derivatives 4.4 0.5 - Net gains or losses on disposals of non-current assets (7.5) 5.3 - Unrealized foreign exchange differences (9.5) 2.3 - Net financing costs 18.5 21.8 - Income taxes 111.8 158.3 - Share-based payment expense 26.5 26.9 '- Other non-cash items21 67.3 (3.6) Cash Flow From Operating Activities Before Changes In Working Capital Requirement 1,141.2 1,088.6 - (Increase)/decrease in inventories (19.9) (4.4) - (Increase)/decrease in trade receivables (86.8) (65.8) - Increase/(decrease) in trade payables 29.1 80.9 - Net change in income tax liability 0.0 0.0 - Net change in other operating assets and liabilities 38.5 (24.9) Change in working capital requirement related to operating activities (39.1) (14.2) Tax paid (130.7) (181.1) NET CASH PROVIDED (USED) BY OPERATING ACTIVITIES 971.4 893.3 Acquisition of property, plant & equipment (96.6) (87.7) Acquisition of intangible assets (156.3) (330.2) Proceeds from disposal of intangible assets and property, plant & equipment 10.0 1.0 Acquisition of shares in non-consolidated companies (7.8) (28.4) Impact of changes in the consolidation scope (131.5) 17.4 Change in working capital related to investment activities (89.5) 98.6 Other cash flow related to investment activities 13.2 (2.8) NET CASH PROVIDED (USED) BY INVESTMENT ACTIVITIES (458.6) (332.0) Additional long-term borrowings 16.0 29.4 Repayment of long-term borrowings (1.1) (0.6) Additional short-term borrowings 1,212.8 657.0 Repayment of short-term borrowings (1,262.2) (965.4) Contingent payments related to acquisitions (0.1) 0.1 Capital increase 0.0 0.0 Treasury shares (11.3) (36.7) Distributions paid by Ipsen S.A. (99.3) (82.9) Dividends paid by subsidiaries to non-controlling interests (0.9) (0.2) Change in working capital related to financing activities 0.0 (1.0) Paid interests (18.2) (21.5) NET CASH PROVIDED (USED) BY FINANCING ACTIVITIES (164.2) (421.8) CHANGE IN CASH AND CASH EQUIVALENTS FROM CONTINUING ACTIVITIES 348.6 139.5 CHANGE IN CASH AND CASH EQUIVALENTS FROM DISCONTINUED ACTIVITIES 1.9 24.1 Impact Of Exchange Rate Fluctuations 5.9 5.8 CLOSING CASH AND CASH EQUIVALENTS 1,165.5 809.1 Appendix 3.2: consolidated net cash flow statement FY 2022 FY 2021 €m €m Opening Net Cash/(Debt)22 28.0 (388.0) CORE OPERATING INCOME 1,115.4 983.1 Non-cash items 105.1 143.4 (Increase) /decrease in inventories (19.9) (4.4) (Increase) / decrease in trade receivables (86.8) (65.8) Increase / (decrease) in trade payables 29.1 80.9 Change In Operating Working Capital Requirement (77.6) 10.7 Change in income tax liability 38.4 (36.0) Change in other operating assets and liabilities (excluding milestones received) 39.1 10.7 Other Changes In Working Capital Requirement 77.4 (25.3) Acquisition of property, plant & equipment (96.6) (87.7) Acquisition of intangible assets (excluding milestones paid) (46.0) (30.6) Disposal of fixed assets 1.5 (0.1) Change in working capital related to investment activities 0.6 8.6 Net capital expenditures (excluding milestones paid) (140.6) (109.7) Dividends received from entities accounted for using the equity method 0.0 0.0 Operating Cash Flow 1,079.6 1,002.3 Other non-core operating income and expenses and restructuring costs (63.3) (48.7) Financial income (23.6) (28.9) Current income tax (167.2) (144.8) Other operating cash flow (8.3) 0.9 Free Cash Flow 817.2 780.7 Distributions paid (including payout to non-controlling interests) (100.2) (83.1) Acquisition of shares in non-consolidated companies (7.8) (10.6) Acquisition of other financial assets (0.1) 0.0 Impact of changes in consolidation scope23 (400.8) 13.7 Milestones paid24 (200.5) (280.1) Milestones received 12.5 25.2 Other Business Development operations 32.0 11.5 Net Investments (Business Development And Milestones) (564.5) (240.4) Share buyback (11.3) (36.7) FX on net indebtedness (20.4) (30.3) Change in cash / (debt) from discontinued activities 249.0 25.7 Other 1.0 0.0 Shareholders Return And External Growth Operations (446.4) (364.7) CHANGE IN NET CASH/(DEBT) 370.8 416.0 Closing Net Cash/(Debt) 398.8 28.0 Appendix 4: bridges from IFRS Consolidated Net Profit to Core Consolidated Net Profit FY 2022 IFRS CORE FY 2022 Amortization of intangible assets (excl software) Other operating income or expenses Restructuring Impairment losses Other FY 2022 €m €m €m €m €m €m €m Total Sales 3,025.0 — — — — — 3,025.0 Other revenue 131.5 — — — — — 131.5 Total Revenue 3,156.4 — — — — — 3,156.4 Cost of goods sold (527.7) — — — — — (527.7) Selling expenses (833.4) — — — — — (833.4) Research and development expenses (445.3) — — — — — (445.3) General and administrative expenses (205.8) — — — — — (205.8) Other operating income 32.1 — (31.7) — — — 0.4 Other operating expenses (305.1) 103.6 172.3 — — — (29.2) Restructuring costs (26.9) — — 26.9 — — — Impairment losses (114.3) — — — 114.3 — — Operating Income 729.9 103.6 140.6 26.9 114.3 — 1,115.4 Net financing costs (18.5) — — — — — (18.5) Other financial income and expense (5.5) — — — — (7.9) (13.4) Income taxes (112.3) (24.9) (35.1) (6.8) (28.3) (3.4) (210.8) Share of profit/(loss) from equity-accounted companies (1.5) — — — — 1.2 (0.3) Net Profit/(Loss) From Continuing Operations 592.1 78.7 105.4 20.2 86.1 (10.1) 872.4 Net profit/(loss) from discontinued operations 55.4 — — — — (55.4) — Consolidated Net Profit 647.5 78.7 105.4 20.2 86.1 (65.5) 872.4 – Attributable to shareholders of Ipsen S.A. 648.6 78.7 105.4 20.2 86.1 (65.5) 873.5 – Attributable to non-controlling interests (1.1) — — — — (0.1) (1.3) Earnings Per Share Fully Diluted – Attributable To Ipsen S.A. Shareholders (In € Per Share) €7.81 €0.95 €1.27 €0.24 €1.04 (€0.79) €10.51 The reconciliation items between core consolidated net profit and IFRS consolidated net profit are described in the paragraph ‘From core financial measures to IFRS reported figures’. FY 2021 IFRS CORE FY 2021 Amortization of intangible assets (excl software) Other operating income or expenses Restructuring Impairment losses Other FY 2021 €m €m €m €m €m €m €m Total Sales 2,643.3 — — — — — 2,643.3 Other revenues 105.4 — — — — — 105.4 Total Revenue 2,748.6 — — — — — 2,748.6 Cost of goods sold (438.6) — — — — — (438.6) Selling expenses (728.1) — — — — — (728.1) Research and development expenses (424.4) — — — — — (424.4) General and administrative expenses (188.2) — — — — — (188.2) Other operating income 53.1 — (39.2) — — — 13.9 Other operating expenses (169.0) 79.4 89.5 — — — (0.1) Restructuring costs (19.6) 0.0 0.0 19.6 — — 0.0 Impairment losses (9.1) 0.0 0.0 0.0 9.1 — 0.0 Operating Income 824.7 79.4 50.3 19.6 9.1 — 983.1 Net financing costs (21.8) — — — — — (21.8) Other financial income and expense (13.8) — — — — (0.7) (14.5) Income taxes (158.3) (19.7) (14.1) (5.0) (2.6) (7.4) (207.1) Share of profit/(loss) from equity-accounted companies 0.4 — — — — — 0.4 Net Profit/(Loss) From Continuing Operations 631.2 59.6 36.3 14.6 6.5 (8.1) 740.1 Net profit/(loss) from discontinued operations 15.5 — — — — (15.5) — Consolidated Net Profit 646.7 59.6 36.3 14.6 6.5 (23.6) 740.1 – Attributable to shareholders of Ipsen S.A. 646.6 59.6 36.3 14.6 6.5 (23.6) 740.0 – Attributable to non-controlling interests 0.1 — — — — — 0.1 Earnings Per Share Fully Diluted – Attributable To Ipsen S.A. Shareholders (In € Per Share) €7.76 €0.72 €0.44 €0.18 €0.08 (€0.28) €8.88 Appendix 5.1: full-year geographic breakdowns of total sales by medicine FY Total North America Europe Rest of World FY 2022 FY 2021 % change FY 2022 FY 2021 % change FY 2022 FY 2021 % change FY 2022 FY 2021 % change €m €m Actual CER25 €m €m Actual CER25 €m €m Actual CER25 €m €m Actual CER25 Oncology 2,379.5 2,153.5 10.5% 4.7% 864.4 799.0 8.2% -3.6% 1,043.9 1,021.7 2.2% 1.9% 471.2 332.8 41.6% 33.5% Somatuline 1,218.0 1,202.7 1.3% -5.6% 706.5 680.7 3.8% -7.5% 379.1 429.0 -11.6% -11.6% 132.5 93.0 42.4% 36.1% Decapeptyl 529.7 459.6 15.3% 12.4% 0.0 0.0 — — 297.3 274.0 8.5% 8.5% 232.4 185.6 25.2% 18.1% Cabometyx 448.7 354.6 26.6% 23.9% 17.4 14.0 24.0% 14.5% 327.6 287.0 14.2% 14.0% 103.7 53.6 93.6% 79.1% Onivyde 162.4 127.4 27.4% 14.1% 127.6 103.8 22.9% 9.4% 32.4 23.1 39.9% 28.1% 2.4 0.5 n/a n/a Tazverik 12.7 0.0 n/a n/a 12.7 0.0 n/a n/a 0.0 0.0 — — 0.0 0.0 — — Other Oncology 8.0 9.1 -12.2% -12.3% 0.3 0.6 -45.0% -49.2% 7.5 8.5 -10.9% -10.7% 0.2 0.1 n/a n/a Neuroscience 604.4 440.7 37.2% 29.7% 160.1 106.1 50.9% 34.7% 161.4 147.2 9.7% 9.8% 282.9 187.4 51.0% 42.5% Dysport 593.6 434.6 36.6% 29.4% 160.1 106.1 50.9% 34.7% 161.4 147.2 9.7% 9.8% 272.0 181.3 50.0% 42.2% Other Neuroscience 10.8 6.1 78.8% 52.1% 0.0 0.0 — — 0.0 0.0 — — 10.8 6.1 78.8% 52.1% Rare Diseases 41.1 49.1 -16.4% -18.3% 7.6 11.2 -32.1% -39.5% 31.9 36.7 -13.0% -13.1% 1.6 1.3 25.4% 16.6% NutropinAq 27.2 32.0 -15.1% -15.3% 0.0 0.0 — — 26.1 30.9 -15.7% -15.8% 1.1 1.1 0.1% -2.3% Increlex 13.9 17.1 -18.7% -23.8% 7.6 11.2 -32.1% -39.5% 5.9 5.8 1.1% 1.3% 0.5 0.2 n/a n/a Total Sales 3,025.0 2,643.3 14.4% 8.5% 1,032.1 916.3 12.6% 0.4% 1,237.3 1,205.5 2.6% 2.4% 755.6 521.4 44.9% 36.7% Appendix 5.2: quarterly geographic breakdowns of total sales by medicine Q4 Total North America Europe Rest of World Q4 2022 Q4 2021 % change Q4 2022 Q4 2021 % change Q4 2022 Q4 2021 % change Q4 2022 Q4 2021 % change €m €m Actual CER26 €m €m Actual CER26 €m €m Actual CER26 €m €m Actual CER26 Oncology 612.3 588.1 4.1% -1.1% 229.9 228.2 0.8% -10.3% 254.6 265.5 -4.1% -3.7% 127.7 94.4 35.4% 27.9% Somatuline 306.1 328.3 -6.8% -13.3% 181.0 195.4 -7.4% -17.6% 86.3 107 -19.3% -18.7% 38.8 26 49.4% 40.3% Decapeptyl 133.7 127.0 5.3% 3.9% 0.0 0.0 — — 76.1 73.6 3.3% 3.7% 57.7 53.4 8.0% 4.3% Cabometyx 121.0 96.0 26.1% 23.1% 4.5 4.1 8.8% 3.8% 85.2 77 10.7% 11.0% 31.3 14.8 n/a 91.8% Onivyde 40.4 34.4 17.3% 5.9% 34.5 28.6 20.6% 7.3% 5.9 5.7 3.4% 0.7% 0.0 0.1 n/a n/a Tazverik 9.9 0.0 n/a n/a 9.9 0.0 n/a n/a 0.0 0.0 n/a n/a 0.0 0.0 — — Other Oncology 1.1 2.4 -52.0% -51.6% 0.1 0.1 -44.5% -45.9% 1.1 2.2 -50.8% -50.2% 0.0 0.1 n/a n/a Neuroscience 196.7 131.1 50.1% 40.6% 43.4 35.3 23.0% 10.5% 50.6 44.2 14.3% 15.0% 102.7 51.6 99.3% 82.2% Dysport 193.2 129.3 49.4% 40.4% 43.4 35.3 23.0% 10.5% 50.6 44.2 14.3% 15.0% 99.3 49.8 99.3% 82.9% Other Neuroscience 3.5 1.7 99.3% 59.7% 0.0 0.0 — — 0.0 0.0 — — 3.5 1.7 99.3% 59.7% Rare Diseases 7.5 11.8 -37.0% -36.9% -0.5 3.0 n/a n/a 7.4 8.5 -13.1% -13.0% 0.5 0.3 63.3% 54.3% NutropinAq 6.4 7.5 -14.8% -14.8% 0.0 0.0 — — 6.1 7.2 -15.0% -15.0% 0.3 0.3 -9.8% -10.5% Increlex 1.2 4.3 -73.1% -73.7% -0.4 3.0 n/a n/a 1.3 1.3 -3.1% -2.6% 0.3 0.0 n/a n/a Total Sales 816.4 731.0 11.7% 5.8% 272.9 266.5 2.4% -8.7% 312.6 318.3 -1.8% -1.4% 231.0 146.2 57.9% 47.4% Forward-looking statements The forward-looking statements, objectives and targets contained herein are based on Ipsen’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 Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. 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 Ipsen. 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 medicine 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. Ipsen must face or might face competition from generic medicine 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 Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical 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 medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen 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 Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen 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. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com. 1 At constant exchange rates (CER), which exclude any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 2 Dysport® (botulinum toxin type A), Decapeptyl® (triptorelin), Cabometyx® (cabozantinib) and Onivyde® (irinotecan). 3 Extract of consolidated results. The Company’s auditors performed an audit of the consolidated financial statements. 4 Decided by the Ipsen SA Board of Directors and to be proposed at the annual shareholders’ meeting on 31 May 2023. 5 Net cash excluding contingent liabilities (earnouts and CVR), previously part of the net cash/(debt) definition. 6 FY 2021 net cash of €28.0m adjusted to exclude contingent liabilities (versus FY 2021 reported net debt of €126.4m) 7 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 8 The acquisition of Albireo, anticipated to close in Q1 2023, is subject to the satisfaction of customary deal closing conditions. 9 The Committee for Medicinal Products for Human Use, the European Medicines Agency's committee responsible for human medicines. 10 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 11 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 12 Defined in this announcement as the E.U., the U.K., Iceland, Liechtenstein, Norway and Switzerland. 13 Contingent value rights. 14 Earnings per share. 15 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 16 Financial liabilities mainly exclude €11.4m in derivative instruments related to commercial operations in FY 2022, compared with €10.7m in FY 2021. 17 Net cash/(debt): derivative instruments booked in financial assets and related to financial operations, cash and cash equivalents, less bank overdrafts, bank loans and other financial liabilities and excluding financial derivative instruments on commercial operations. 18 The data published for FY 2021 has been restated to account for the impacts related to the sale of the CHC (see note 3.2 to the consolidated financial statements for the year ended 31 December 2022). 19 The financial statements were restated to retroactively apply the IFRIC decision on Software as a Service (SaaS) as from 1 January 2021 (see note 11.1 to the consolidated financial statements for the year ended 31 December 2022). Data related to FY 2021 have been restated after changing the presentation of assets and liabilities associated with contingent payments (see note 2.2 of the accounting principles). Assets totalling €42.4m linked to contingent payments have been reclassified from the ‘Current financial assets’ line item to the ‘Other current assets’ line item. Liabilities totalling €109.3m linked to contingent payments have been reclassified from the ‘Non-current financial liabilities’ line item to the ‘Other non-current liabilities’ line item and another €45.1m were reclassified from the ‘Current financial liabilities’ line item to the ‘Current financial liabilities’ line item. 20 The data published for FY 2021 have been restated to account for the impacts related to the sale of the CHC business (see note 3.2 to the consolidated financial statements for the year ended 31 December 2022). 21 Other items without impact on cash and cash equivalents mainly correspond to a change in fair value of contingent assets and liabilities related to business combinations. 22 FY 2022 opening net cash at €28.0m versus FY 2021 closing net debt of €126.4m, reflecting the reclassification of the contingent liabilities (earnout and CVR) - previously part of the net-debt definition. 23 In FY 2022, impact of change in consolidation scope includes the acquisition of Epizyme for €400.3m. In FY 2021, the impact of change in consolidation scope included the proceeds from the divestiture in equity-accounted companies for €24.0m and the purchase of an equity investment in BAKX Therapeutics Inc. for €10.3m. 24 Milestones paid in 2022 correspond to the upfront paid to Marengo Therapeutics for €44.9m, additional Cabometyx commercial and regulatory milestones paid to Exelixis for €122.8m and a development milestone for Fidrisertib paid to Blueprint Medicines for €28.5m. Milestones paid in 2021 correspond to payments subject to the terms and conditions set out in the Group’s partnership agreements, including €148.0m related to the partnership with GENFIT and €51.3m milestones paid to Exelixis. 25 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. 26 At CER, which excludes any foreign-exchange impact by recalculating the performance for the relevant period by applying the exchange rates used for the prior period. Attachment FY 2022 – Results announcement

- Acromegaly and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare diseases that require life-long chronic treatment. Monthly somatostatin analog (SSA) injections are the standard of care as first-line medical treatment. - Debiopharm is developing Debio 4126, a novel 3-month extended-release octreotide formulation, to optimize acromegaly and GEP-NET patient care by reducing injection frequency, which translates into an improved quality of life and less time spent with medical visits. - Debio 4126 is currently being investigated in two clinical studies. One of them (study Debio 4126-102) is a phase 1b study in patients with acromegaly or GEP-NETs. This study was designed to characterize the pharmacokinetic, pharmacodynamic, efficacy, safety, and tolerability profiles of Debio 4126 administered intramuscularly (IM) every 3 months over an extended period. LAUSANNE, Switzerland, Jan. 12, 2023 /PRNewswire/ -- Debiopharm (), a Swiss-based, global biopharmaceutical company, today announced that the first patient was dosed with Debio 4126, a 3-month extended-release formulation of octreotide, in their open-label, non-randomized, single-arm, multicenter phase 1b study (Debio 4126-102). The study is composed of two patient cohorts – 1 group of patients with acromegaly and 1 group with functioning GEP-NETs Patients will receive 4 injections of Debio 4126 for a total treatment duration of 48 weeks. Debio 4126 is currently the only 3-month SSA in clinical development. The development of Debio 4126 arises from Debiopharm's wish to leverage their modified-release Debiosphere™ technology to alleviate the treatment burden of patients with rare diseases, such as acromegaly and GEP-NETs, by reducing the injection frequency to 4 injections per year. In healthy volunteers, Debio 4126, an extended-release formulation of octreotide, exhibited good bioavailability and sustained release for up to 3 months.1 It has the potential to offer efficacy and safety similar to those of marketed 1-month SSAs. If successful, Debio 4126 will equip healthcare professionals with a new, more convenient option for treating acromegalic and GEP/NET patients. "Going into this 2-year long phase 1b trial, we look forward to ascertaining the benefits of this extended-release formulation. We believe that patient quality of life can be improved through the substantially reduced number of injections, from 12 to 4/year," explained Dr Simona Ispas Jouron, Senior Medical Director, Endocrinology & Rare Diseases at Debiopharm. Prior to this compound, Debiopharm's extended-release formulation expertise extends over more than 35 years with the development of multiple formulations of agonist analogue triptorelin, benefiting patients affected by prostate cancer, breast cancer, endometriosis, central precocious puberty (CPP), and uterine myomas. "The success of triptorelin is linked to our modified-release Debiosphere™ technology that has contributed to the improvement of the quality of life of patients treated long-term, particularly with our 1, 3 and 6-month formulations of triptorelin and now with Debio 4126. This formulation adds significant value to an efficacious and safe standard of care." expressed Bertrand Ducrey, CEO of Debiopharm. About Acromegaly Acromegaly is a rare chronic disorder caused by excessive GH secretion by pituitary adenomas, with more than 95% of cases being benign.2 The condition most commonly affects middle-aged adults, with a slight predominance of female patients (52-60%)3 and equal distribution among ethnicities. The disease is clinically diagnosed based on characteristic symptoms, including progressive skeletal and soft tissue overgrowth, mainly at the extremities (hands and feet) and head. Diagnosis is confirmed biochemically via increased serum concentrations of GH and IGF-1. Acromegaly is associated with a twofold increase in mortality relative to that expected in the general population, mostly due to cardiovascular events. Associated risk factors include hypertension, glucose metabolism abnormalities, dyslipidemia, abdominal adiposity, and peripheral insulin resistance (metabolic syndrome). Untreated acromegaly is associated with a reduced quality of life and life expectancy shortened by approximately 10 years.2 About Gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) GEP-NETs are rare and complex malignant solid tumors, derived from neuroendocrine cells, occurring in various sites along the gastrointestinal tract. Although these tumors have been considered rare, the most recent data from the US Surveillance Epidemiology and End Results show an increase of more than 400% in the incidence of these diseases over the period from 1973 to 2004. 4 Age at diagnosis is generally younger than 50 years, and these tumors may arise sporadically or because of hereditary predisposition. Survival of patients with GEP-NETs depends on the stage and histology. Patients with well and moderately differentiated metastases have a 5-year survival probability of 35%, while poorly differentiated metastases lead to a 5-year survival probability of 4%4 About Debio 4126 Octreotide is a synthetic octapeptide that mimics the pharmacology of endogenous somatostatin (SST). Currently, octreotide is available as immediate-release (Sandostatin®) and 4-week long-release formulations (Sandostatin LAR®). Debio 4126 is a novel, 3-month extended-release formulation of octreotide being developed by Debiopharm. Debiopharm's commitment to patients Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. We identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select pharmaceutical commercialization partners to maximize patient access globally. For more information, please visit We are on Twitter. Follow us @DebiopharmNews at Debiopharm Contact Dawn Bonine Head of Communications [email protected] Tel: +41 (0)21 321 01 11 References [1] Bellon A, et al. ENEA. 2022. [2] Chanson P, et al. Pituitary tumours: acromegaly. Best Pract Res Clin Endocrinol Metab. 2009;23(5):555-74. [3] Fleseriu M, et al. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol 2022 Nov;10(11):804-826 [4] Yao, et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 26,18 (2008): 3063-72. SOURCE Debiopharm International SA