Palovarotene

Pictured: FDA's signage at its campus in Maryland/iStock, JHVEPhoto The FDA on Tuesday approved Ipsen’s Onivyde (irinotecan liposome injection), when used in combination with three chemotherapeutic drugs, for the treatment of newly diagnosed patients with metastatic pancreatic adenocarcinoma. The Onivyde-based regimen, dubbed Nalirifox, is the first frontline approval for metastatic pancreatic adenocarcinoma (mPDAC) in more than 10 years, Julie Fleshman, CEO of patient advocacy group Pancreatic Cancer Action Network, said in a statement. Christelle Huguet, Ipsen’s executive vice president and head of R&D, said in a statement that Onivyde’s latest approval “can now offer a potential new standard-of-care treatment option with proven survival benefits” for mPDAC patients. Tuesday’s label expansion is based on data from the Phase III NAPOLI 3 trial, a randomized, open-label pivotal study with 770 mPDAC patients enrolled, all of whom had undergone no prior treatment. In January 2023, Ipsen posted data from NAPOLI 3, demonstrating that the Nalirifox regimen—which combines Onivyde with fluorouracil, oxaliplatin and leucovorin—boosted overall survival by a statistically significant 17% compared to standard of care, consisting of nab-paclitaxel and gemcitabine. Nalirifox also improved progression-free survival by 31%. According to Ipsen’s announcement, NAPOLI 3 is the first positive Phase III trial in mPDAC that shows better overall survival compared to the current standard-of-care regimen, and Onivyde is the only FDA-approved treatment regimen to demonstrate efficacy in two Phase III trials across lines of therapy in mPDAC. Onivyde encloses the chemotherapeutic drug irinotecan in liposomes, which can accumulate inside tumors over time, slowly releasing a toxic payload. By blocking the topoisomerase I enzyme, which is involved in DNA replication and is crucial for cell proliferation, Onivyde exerts its cancer-killing effects. The FDA first approved Onivyde, in combination with fluorouracil and leucovorin, in 2015 for mPDAC patients who had progressed after gemcitabine-based treatment. Tuesday’s label expansion continues a winning streak for Ipsen. In June 2023, the biotech secured the support of the Metabolic Drugs Advisory Committee, voting 10–4 to recommend the approval of its fibrodysplasia ossificans progressiva therapy palovarotene. In August 2023, the FDA followed the advice of its external experts and approved the therapy, which now carries the brand name Sohonos. Ipsen has also been on a clinical roll. In June 2023, the company revealed topline data from its Phase III ELATIVE trial for elafibranor, demonstrating a significantly higher rate of clinically meaningful cholestasis versus placebo in patients with primary biliary cholangitis. Ipsen, along with partner Genfit, followed this up with strong biochemical response data in November 2023. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Total-sales growth in FY 2023 of 6.7% at CER1 (3.4% as reported) included strong sales from the growth platforms2 and good contributions from the new medicines. A core operating margin of 32.0% (IFRS operating margin of 26.1%), based on further enrichment of the pipeline and accelerated R&D investment, mainly from recent acquisitions Financial guidance for 20243 comprises total-sales growth4 greater than 6.0% at CER1 and a core operating margin5 around 30% of total sales, including the impact of four potential launches and an advancing pipeline A new phase of growth and mid-term financial outlook were outlined at the December 2023 capital-markets day PARIS, FRANCE, 8 February 2024 - Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-care biopharmaceutical company, today presents its financial results for the year and final quarter of 2023. Extract of consolidated results for FY 2023 and FY 20226: FY 2023 FY 2022 % change €m €m Actual CER1 Total Sales 3,127.5 3,025.0 3.4% 6.7% Core Operating Income 1,001.0 1,115.4 -10.3% Core operating margin 32.0% 36.9% -4.9% pts Core Consolidated Net Profit 765.5 872.4 -12.3% Core earnings per share (fully diluted) €9.15 €10.51 -13.0% IFRS Operating Income 816.0 729.9 11.8% IFRS operating margin 26.1% 24.1% 2.0% pts IFRS Consolidated Net Profit 647.2 647.5 - IFRS earnings per share (fully diluted) €7.73 €7.81 -1.0% Free Cash Flow 710.9 817.2 -13.0% Closing net cash 65.1 398.8 -83.7% “Solid results in the year have provided an excellent platform for Ipsen in 2024, an exciting period in which we anticipate four launches and further opportunities to expand the pipeline”, commented David Loew, Chief Executive Officer, Ipsen. “As Ipsen transforms, improving execution is supporting consistent sales growth, while the productive pipeline is yielding further encouraging results for patients. “Our external-innovation strategy, underpinned by a strong balance sheet, continues to extend the number of potential medicines across our three therapeutic areas. Following the acquisition of Albireo in 2023 and the successful launch of Bylvay, we look forward to more milestones this year and enriching the pipeline over time through additional external-innovation transactions. I am confident that this strategy will deliver more medicines for patients and ensure the sustainable growth of Ipsen.” 2023 progress Ipsen continued to deliver successfully in 2023 on its strategy, Focus. Together. For patients and society. The growth platforms produced a further double-digit performance, with Cabometyx and Dysport up by 22.9%7 and 14.5%7, respectively. There were contributions from the new medicines, Bylvay® (odevixibat), Sohonos® (palovarotene) and Tazverik® (tazemetostat), while Somatuline® (lanreotide), continuing its gradual erosion (-10.4%7), represented only 34% of total sales (FY 2022: 40%). The decline in the core operating margin to 32.0% (FY 2022: 36.9%) reflected enhanced investment from the acquisitions of Albireo and Epizyme, including a higher level of R&D expenses to fund the new pipeline. Ipsen ended the year with net cash of €65.1m, driven by solid free cash-flow generation of €710.9m. In March 2023, Ipsen enriched its Rare Disease portfolio and pipeline by acquiring Albireo, a leading innovator in bile-acid modulators to treat pediatric and adult cholestatic liver diseases. The primary focus of the transaction was Bylvay, a potent, once-daily, oral, non-systemic ileal bile acid transport inhibitor. Favorable pipeline developments in 2023 included positive results from the Phase III trials of elafibranor in primary biliary cholangitis (PBC) and Cabometyx in prostate cancer, respectively. Regulatory submission acceptances were received for Onivyde in first-line pancreatic ductal adenocarcinoma (1L PDAC), as well as for elafibranor. Sohonos and Bylvay were also granted approval during the year by the U.S. Food and Drug Administration (FDA) in fibrodysplasia ossificans progressiva (FOP) and Alagille syndrome, respectively. 2024 priorities and financial guidance Ipsen anticipates four commercial launches in 2024, following regulatory decisions for Onivyde in 1L PDAC in the U.S (H1), elafibranor in second-line PBC in the U.S. (H1) and in the E.U. (H2), as well as odevixibat in Alagille syndrome in the E.U. (H2). Sohonos, in FOP, was recently launched in the U.S. The Company will continue to drive benefits from its global efficiencies program, leveraging its current platform, which provide significant further investment for launches and the pipeline. Ipsen has set the following financial guidance for FY 2024, which excludes any impact from potential late-stage external-innovation transactions: Total-sales growth greater than 6.0%, at constant currency. Based on the average level of exchange rates in January 2024, an adverse impact on total sales of around 1% from currencies is expected Core operating margin around 30% of total sales, which includes additional R&D expenses from anticipated early and mid-stage external-innovation opportunities Guidance on total sales incorporates expectations for Somatuline of further generic lanreotide products in the U.S and E.U. Capital-markets day and mid-term financial outlook Ipsen outlined its next phase of growth at its capital-market day, held in December 2023. Several current and potential near-term launches are set to be complemented by many pipeline milestones over the mid-term to build a strengthened and diversified business, including a combination of seven anticipated and current medicines, each with expected peak sales of at least €500m. This will be augmented by an active external-innovation strategy, designed to provide a platform to drive sustainable pipeline growth. The Company outlined the following mid-term financial outlook8: Total-sales average growth of at least 7% per year for the period 2023-2027 at constant exchange rates A core operating margin in 2027 of at least 32% of total sales Environment, Social and Governance: Generation Ipsen Ipsen presented an ambitious sustainability roadmap at the aforementioned capital-markets day, based on Generation Ipsen, the strategy focused on four pillars: Environment, Patients, People and Governance. Good progress was made in 2023. Ipsen is committed to science-based reductions in greenhouse-gas emissions across the entire value chain. The Company achieved a 36% reduction in Scope 1 & 2 emissions in 2023 vs the 2019 baseline. Scope 3 reductions in 2023, against the same baseline year, amounted to 29%. Ipsen has the ambition to be carbon-neutral by the end of 2025 and reach net-zero emissions by 2045. With a key focus on patients, the Company has made progress to reduce the length of time between clinical-trial readouts and non-FDA/EMA9 regulatory submissions by 25%. In 2023, 53% of the GLT was comprised of women versus 48% in 2022, while 43% of colleagues were engaged in healthcare or environmental projects in 2023. Finally, ISO37001 certification for anti-corruption management was renewed in the year. Consolidated financial statements The Board of Directors approved the consolidated financial statements on 7 February 2024. 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 2pm CET. 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 25 April 2024. Notes All financial figures are in € millions (€m). The performance shown in this announcement covers the twelve-month period to 31 December 2023 (FY 2023) and the three-month period to 31 December 2023 (Q4 2023), compared to the twelve-month period to 31 December 2022 (FY 2022) and the three-month period to 31 December 2022 (Q4 2022), respectively, unless stated otherwise. Commentary is based on the performance in FY 2023, unless stated otherwise. About Ipsen We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries. Ipsen 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. Ipsen contacts Investors Craig Marks +44 (0)7584 349 193 Nicolas Bogler +33 6 52 19 98 92 Media Amy Wolf +41 79 576 07 23 Ioana Piscociu +33 6 69 09 12 96 Disclaimers and/or 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® (abobotulinumtoxinA), Decapeptyl® (triptorelin), Cabometyx® (cabozantinib) and Onivyde® (irinotecan). 3 Excludes any impact from potential late-stage external-innovation transactions. 4 Incorporates expectations for Somatuline of further generic-lanreotide products in the U.S and E.U. and excluding, based on the average level of exchange rates in January 2024, an adverse expected impact on total sales of around 1% from currencies. 5 Includes additional R&D expenses from anticipated early and mid-stage external-innovation opportunities. 6 Extract of consolidated results. The Company’s auditors performed an audit of the consolidated financial statements. 7 At 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. 8 Excluding the impact of any potential additional late-stage (Phase III clinical development or later) external-innovation opportunities. 9 European Medicines Agency. Attachment FY 2023 - results announcement