Cystitis, Interstitial

Hyloris Reports Full Year Results for 2023 & Provides Business Outlook Total revenue and other income amounted to €4.4 millionStronger growth expected in 2024 of both sales and gross margin, mainly fueled by the recent launch in the U.S. of Maxigesic® IV and Podofilox gel, the global roll out of Maxigesic IV® and commercial dealsIncreased operating R&D expenses while net operating cash outflow remained stable versus 2022Significant R&D progress including clinical and regulatory achievements with multiple NDA submissions expected within the next 15 monthsAttractive commercial deals, including an out-licensing deal for Atomoxetine Oral Liquid in CanadaPromising new product candidates driving innovation, targeting a portfolio of 30 assets by 2025€30.2 million in cash & cash equivalents, no financial debtWebcast on 14 March 2024 at 1PM GMT / 2PM CET/ 9AM EST (Register here) Liège, Belgium – 14 March 2023 – 7AM CET – Regulated Information – Inside Information - Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announces its financial and operational results for the year ending on 31 December 2023, as well as its business outlook for 2024. Stijn Van Rompay, Chief Executive Officer of Hyloris, commented: “Despite a challenging year for the global healthcare industry, 2023 proved to be a year of significant accomplishment for Hyloris. As a company built on the unique and successful strategy of repurposing and reformulating existing pharmaceuticals, we achieved a major milestone with the U.S. approval of Maxigesic® IV in partnership with AFT Pharmaceuticals, marking a crucial step in delivering this innovative pain management solution to American patients. Additionally, approval was secured for Podofilox gel, the first generic version of Condylox® Gel, expanding access to this medication. Our unwavering commitment to research and development yielded impressive progress across our diverse product pipeline. These advancements solidify our position as a leader in providing solutions to unmet medical needs in the years to come. We are incredibly proud of our team's dedication and resilience throughout this transformative year. Looking ahead to 2024, Hyloris is poised for continued growth and innovation. We plan to significantly bolster our pipeline with the addition of several new product candidates addressing critical unmet medical needs. Recent additions, including treatments for Vulvar Lichen Sclerosus and Burning Mouth Syndrome, demonstrate our commitment to expanding our portfolio and addressing a wider range of patient needs. We remain confident in our ability to continue delivering value to patients, shareholders, and all stakeholders and expect continued growth beyond 2024. Commercial Highlights Maxigesic® IV is a patented, unique combination, intravenous formulation for the treatment of post-operative pain and is currently licensed to partners covering over 100 countries across the globe. During 2023 and early 2024: A marketing authorization was granted by the United States Food and Drug Administration (FDA) in October 2023.Hikma Pharmaceuticals (Hikma), a leading supplier of complex injectable hospital products, has launched the product in the U.S. under the tradename Combogesic® IV. An exclusive license and distribution agreement had previously been signed between Hyloris’ partner AFT Pharmaceuticals (AFT) and Hikma.Additional submissions for marketing authorization were made in 13 countries in the Middle East, Africa, Latin America, and Asia.Additional marketing authorizations have been granted in 8 countries including Poland, South Africa, and Spain. In early 2024, Health Canada granted approval bringing the total number of approvals to 50.Launches occurred in 14 countries including Norway, Singapore, Belgium, The Netherlands, the Czech Republic, and Romania. Imminent launches are expected in several additional countries, bringing the total number of countries where Maxigesic® IV will be available up to more than 30. In the United States, chronic opioid usage in patients following surgery averages around 9%, ranging from 4% to 24% among various specialties. Drug overdoses involving opioids resulted in over 80.000 deaths in the U.S. in 2021. Patients who experienced an opioid overdose accounted for nearly $2 billion in annual hospital costs. Sotalol IV is a patented, intravenous formulation of Sotalol for the treatment of atrial fibrillation, and life-threatening ventricular arrhythmias developed for the U.S. Sotalol IV potentially allows to significantly reduce the length of hospital stay and the overall cost of care and potentially improve patient outcomes. Hyloris is taking further steps targeting to increase product related revenues in the future (see also: Ongoing Legal Proceedings). Podofilox Gel (Product previously referenced as HY-016) In December 2023, our partner Padagis US LLC (Padagis) received marketing authorization for Podofilox gel 0.5% from the FDA. Padagis launched the product in December 2023. It is the first generic for Condylox® Gel in the U.S. Podofilox Gel is an antimycotic drug for the topical treatment of external genital and perianal warts caused by certain types of the Human Papilloma Virus (HPV). Around 1% of the sexually active population in the U.S. presents with genital or perianal warts.1 To date there is a vaccine for HPV but no cure. For the 12 months period ending December 2022, Condylox® Gel had U.S. sales of approximately $9 million according to IQVIA Health. Other Commercial Highlights Tranexamic Acid RTU Additional out-licensing agreements were signed for Tranexamic Acid RTU in 2023. These agreements cover a large European country and several major Asian countries, with a combined population of over 60 million people. Previous agreements have been signed in 2021 for Australia, New-Zealand and Canada. In 2023, our licensing partner for Canada submitted an application for approval by Health Canada. Additional regulatory submissions in the partnered territories are in progress, and more out-licensing agreements are expected going forward. An Abbreviated New Drug Application (ANDA) has been submitted to the U.S. FDA. Tranexamic acid injection is an established antifibrinolytic agent used in emergency situations with major hemorrhages and is also used as a prophylactic agent in surgeries. Hyloris is developing a ready-to-use (RTU) formulation for infusion. Atomoxetine Oral Liquid An out-licensing agreement was signed with Kye Pharmaceuticals (Kye) in October 2023. Kye will exclusively commercialize the product in Canada where atomoxetine is currently not available as an oral liquid formulation. The introduction of an oral liquid formulation in the ADHD (Attention Deficit Hyperactivity Disorder) medication category has historically led to significant market share gains2. This suggests a strong potential for Atomoxetine Oral Liquid in Canada, where an estimated 1.8 million people (or 4-6% of adults and 5-7% of children) are diagnosed with ADHD3. ADHD is a chronic condition, with symptoms persisting into adulthood for 60-80% of patients4. Under the terms of the agreement, Hyloris will be eligible to receive attractive sales-related milestone payments (totaling up to USD 7.5 million), and a substantial share of the generated revenue. New Pipeline Product Candidates Our business development team leverages its expertise in existing products, real-world data, and a vast network to identify unmet medical needs. This includes collaborating with healthcare professionals, patient groups, insurers (payors), and industry partners. In 2023 over 87 opportunities were screened and 3 product candidates will meet our investment criteria of €7 million5 in 7 years or less. For product candidates which Hyloris intends to out-license, the strategic goal is to capture a substantial part of the net product margin realized by our commercial partners. Hyloris aims to achieve this by partnering these assets close to regulatory submission, except in countries where additional local clinical trials are required. In general, we will prioritize in-market product sales or profit-based participation over (upfront) milestone payments. We aim to increase our product portfolio to 30 assets by 2025, with a focus on accelerating pipeline growth in the near future. HY-091, a novel topical treatment candidate for Vulvar Lichen Sclerosus (VLS) was announced in January 2024. VLS is a chronic inflammatory condition affecting an estimated 3% of women, causing severe pain, itching, and discomfort, significantly impacting their quality of life. HY-091 is being developed as a convenient and user-friendly treatment specifically designed to target these VLS symptoms. Hyloris has partnered with AFT for co-development, registration, and worldwide commercialization. HY-090, a promising new treatment candidate for Burning Mouth Syndrome (BMS) was announced in December 2023. BMS is a chronic condition affecting millions, primarily postmenopausal women, causing a burning, tingling, or scalding sensation in the mouth for months at a time. While the mouth appears healthy, sufferers may also experience dry mouth or taste alterations, the exact cause of BMS remains unknown. Studies suggest that 0.7% to 5% of individuals in the U.S. might be affected6. Hyloris has partnered with AFT to co-develop and commercialize the product worldwide. HY-088 was announced in January 2023. This novel, proprietary oral formulation will be administered to patients with hypophosphatemia – a condition where the blood level of phosphorus is lower than 2.5mg/dL. Patients can develop hypophosphatemia from either a genetic abnormality (such as Cushing Syndrome or osteomalacia) or an acquired condition (like long-term use of diuretics or phosphate binders). It is estimated hypophosphatemia affects around 5% of hospitalized patients, and a subpopulation needs direct treatment during and/or after their hospital stay. Treatment protocols for patients deficient in phosphate are well-established and have proven useful in other situations of bone mineral imbalance. Oral administration is the preferred way of treating hypophosphatemia, although in most countries no approved drugs exist. Currently, physicians mostly rely on compounded drugs which have, by definition, not been submitted for regulatory scrutiny regarding safety, efficacy, and quality. R&D Update Throughout 2023, Hyloris achieved significant advancements across the entire R&D portfolio, propelling the 18 product candidates and 3 high-barrier generics closer to commercialization. Key milestones were met for multiple programs, and discussions with regulatory agencies and partners are underway to solidify development plans. As a result, Hyloris anticipates submitting multiple INDs (Investigational New Drug applications) and NDAs (New Drug Applications) throughout 2024 and early 2025. Enhanced Capabilities Drive Efficiency Further bolstering our R&D efforts, Hyloris officially opened its new and improved R&D lab at the Montlegia Science Park in June 2023. This on-site facility allows Hyloris to perform drug formulation and analytical activities in-house, streamlining processes and optimizing resource allocation for the expanding pipeline. Cardiovascular Portfolio Hyloris is actively engaged in advancing a comprehensive portfolio dedicated to addressing a wide range of conditions within the largest global treatment category – cardiovascular care. These products are currently progressing through or towards clinical trials, with the aim of significantly enhancing the quality of life for patients. Main highlights for 2023 and selected expected milestones for 2024 include: Aspirin IV: Registration batches have been manufactured and the stability study is ongoing. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. Aspirin IV is an intravenous (IV) formulation of acetylsalicylic acid (ASA) to be used in an emergency setting. Aspirin is not available in the U.S. as an IV product. Currently, most patients suspected of having an emergency cardiovascular event (such as a myocardial infarction or stroke) are immediately given oral aspirin to decrease their risk of morbidity and mortality. Milrinone: The optimization of the extended-release formulation for alcohol resistance marked a significant development milestone. Preparations for a pilot pharmacokinetic (PK) study are in progress. Oral milrinone is being developed as a novel, extended-release formulation offering convenient oral dosing for a selected population of end-stage heart failure (HF) patients who have Left Ventricular Assist Devices (LVADs). HY-074: All non-clinical studies were completed in 2023. A patent application was filed through the Patent Cooperation Treaty (PCT) which allows an applicant to seek patent protection in several different countries – including the U.S. Hyloris is targeting an IND submission for Q2 2024 for the PK bridging study expected to start at the end of 2024. HY-074 is an intravenous formulation of current standard of care treatment for acute coronary syndrome (ACS) to offer faster onset of action, more convenient administration, and dosage control. It is currently available in oral form, which should allow for an optimal switching strategy from the oral form to an IV in a hospital setting. Dofetilide IV: Registration batches have been manufactured and the stability study is ongoing. A CRO has been selected for the required clinical study. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. A pivotal clinical study to support regulatory submission for Dofetilide IV is nearing completion, with results expected by Q3 2024. Additional U.S. patent applications have been filed to bolster the drug's intellectual property protection. Other Value-Added Programs Hyloris, in collaboration with its development partners, is achieving consistent progress on all stages of our value-added programs. Main highlights for 2023 and expected milestones for 2024 include: Tranexamic Acid Oral Mouth Rinse (previously HY-004): A Type A meeting with the FDA resulted in alignment on the phase 3 study protocol. The phase 3 trial began in November 2023, enrolling the first patient in early 2024. Completion of enrollment (Last Patient Last Visit - LPLV) is expected by year-end, with study results anticipated in the first half of 2025. This rinse targets patients on blood thinners (anticoagulant therapies) undergoing dental procedures with a high risk of excessive bleeding. Additionally, Hyloris intends to explore the effectiveness in a wider range of related oral surgery procedures, encompassing both patients with and without bleeding disorders who could benefit from a localized treatment to reduce blood clotting. Miconazole/Domiphen Bromide: Hyloris is co-developing Miconazole/Domiphen Bromide (MCZ/DB) with Purna Female Healthcare, a topical cream combining miconazole and domiphen bromide. This innovative treatment targets Recurrent Vulvovaginal Candidiasis (rVVC), a chronic and often debilitating vaginal yeast infection affecting nearly 1 in 10 women throughout their lives. The Phase 2 clinical trial, completed in late 2023 (Q4), showed promising results. The low-dose group exhibited evidence of delayed disease recurrence at day 29. These findings will be used to design the next clinical trial, scheduled to begin by year-end 2024. MCZ/DB presents a strong scientific and commercial potential for addressing rVVC. AlenuraTM: Hyloris is co-developing Alenura™ with Vaneltix. It is a first-in-class drug candidate designed to bring immediate pain relief to patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS). This chronic condition affects at least 6 million people in the U.S. alone. Alenura™ stands out for its innovative dual mode-of-action. It combines a new, alkalinized form of lidocaine for fast pain relief with heparin to potentially aid in the regeneration of the bladder lining. This unique approach holds promise for providing both immediate symptom relief and long-term benefits for IC/BPS patients. June 2023 marked a significant milestone with the enrollment of the first patient in the Phase 2 clinical trial of Alenura™. This pivotal study will compare the effectiveness of Alenura™ against its individual components (lidocaine and heparin) as well as a placebo. PTX-252: PTX-252 is a novel chelating agent in development for the treatment of Acute Myeloid Leukemia (AML). This product candidate incorporates a novel molecular entity that is a derivative of a known established molecule. This advancement was followed by positive news: Hyloris' co-development partner, Pleco, secured Orphan Drug Designation from the FDA for PTX-252 specifically for AML. PTX-252's potential lies in its ability to potentially improve the effectiveness of existing chemotherapy for AML patients. This is particularly significant as AML affects approximately 160,000 people globally. Previous research suggests a correlation between high levels of toxic metals and lower survival rates in AML patients. A Pre-Investigational New Drug (PIND) meeting with the FDA is planned. Valacyclovir: A successful study demonstrating bioequivalence was completed in 2023. An additional pivotal study can be expected to start and close in H1 of 2024. Registration batches have been manufactured to demonstrate pharmaceutical quality of the product and robustness of the manufacturing process. Hyloris is developing a liquid formulation of valacyclovir which is currently only available in oral solid form. Valayclovir is an antiviral drug commonly used to treat the Herpes Simplex Viruses (HSV) that cause cold sores, genital herpes, chicken pox, and shingles. Management & Board changes The total headcount of the Company grew to 42 people, with several key recruitments occurring over the summer. To enhance the development activities, only limited additional hiring is required. Both the C-level executives and all board members remained in their respective positions, providing continuity in the company's leadership. Business Outlook With 18 reformulated and repurposed molecules, and 3 high-barrier generics, several clinical trials are expected to start and/or finish within 2024. The Company is actively accelerating the growth of its product pipeline, aiming to reach 30 product candidates by 2025. The company is expecting several clinical and regulatory achievements in the next 15 months. Several clinical studies will be initiated or completed. The Company is anticipating multiple NDA submissions to the U.S. FDA and other regulatory agencies. Webcast Details The Company will host a webcast conducted in English to present its 2023 annual results and 2024 Business Outlook, followed by a live Q&A session. The webcast will start on March 14th 2024 at 2PM CET / 1PM GMT / 9AM EST. To join the webcast, please register at the following link: Hyloris: 2023 Full Year Results, Outlook for 2024, and Q&A For those unable to join via webcast, please find dial in information below: Phone Conference ID: 598 167 742# Belgium: +32 4 290 22 87France: +33 1 73 24 00 56Netherlands: +31 20 708 1382Switzerland: +41 43 434 66 31United Kingdom: +44 20 7660 8327United States: +1 347 378 4531Japan: +81 3 4540 5088 Financial Highlights 2023 Year ended 31 December (in € thousand)20232022 Restated*VarianceTotal Revenues and Other income4,4062,38685%Revenues2,8141,951*44%Other operating income1,5924357266%Operating expenses(20,642)(14,024)47%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)44%General and administration expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating result (EBIT)(16,236)(11,638)*40%Net financial result474(127)-473%Income Taxes-(4) Profit/(Loss) for the period(15,762)(11,770)*34%Net operating cash flow(12,726)(12,499)82%Other investment-10,000 Cash and cash equivalents30,19633,457-10%Total cash and Other investment30,19643,457 *See Note: Restatement of the year 2022 and Press Release dated 14th of March 2024 related to restatement for additional information on HY-038 and HY-088. Total Revenue and Other Income In 2023, total revenue and other income increased to €4,406 thousand compared to €2,386 thousand in 2022, which is 85% higher compared to last year. The strong growth is mainly driven by increase of royalties of the 3 early-stage commercialized products, services provided to external partners and non-dilutive funding which we received from a US State Government and the Walloon region in Belgium. Results The Company realized a net loss of €15,762 thousand in 2023, compared to a net loss of €11,770 thousand last year. The net loss is mainly resulting from the increase in R&D expenditure and G&A expenses for supporting the development of the Company. R&D expenditure during 2023 amounted to €14,749 thousand, compared to €10,272 thousand in 2022. The increase was mainly driven by the progressive shift from early to late-stage development of several product candidates as well as the increased headcount of the research and development team leading to additional costs. General and administrative expenses increased to €5,653 thousand in 2023 versus €3,517 thousand in 2022, mainly driven by higher legal costs related to the AltaThera’s litigation compared to last year. The net financial income in 2023 was €474 thousand compared to a net financial loss of €127 thousand in 2022. The positive evolution of the financial result is mainly due to the impact of an active cash management strategy in a context of high short term interest rates both in EURO and USD. As a result, net losses in 2023 increased to €15,762 thousand versus €11,770 thousand in the same period of 2022. Balance Sheet The Company’s non-current assets mainly consist of (1) investments in joint ventures of € 3,801 thousand, (2) intangible assets of €3,828 thousand including capitalized development, purchased assets and in-licensing costs, versus €3,600 thousand in 2022, (3) Right of use assets related to the leasing of the office, lab and cars, (4) shares in Pleco of €1,000 thousand, (5) a prepayment of future royalties to a third party of $700 thousand and (6) a tax credit. Hyloris does not capitalize research and development expenses until the filing for a marketing authorization for the applicable product candidate. Research and development expenditures incurred during the period were accounted for as operating expenses. When an intangible asset is acquired and capitalized, the amortization begins when the asset is available for commercialization. The Company’s current assets mainly consist of €30,196 thousand in cash and cash equivalents on total assets of €47.61 million, and trade and other receivables of €4.1 million. The increase in Right-of-use assets and borrowings is due to the start of the lease for the new lab. The Company received an advance payment related to a government grant from the Walloon region. €43 thousand of this advance is a financial liability and €37 thousand is part of Trade and other liabilities. Cash Position and cash flow The Company maintains its strong cash position, with a current cash and cash equivalents totaled €30,196 thousand at the end of 2023, compared to €43,457 thousand at the end of 2022 (which includes a deposit for an amount of €10 million which has been reclassified to Other investment in 2022). Net cash outflow generated from operating activities was €12,726 thousand in 2023, compared to a net operating cash outflow of €12,499 thousand in 2022. The stable net operating cash outflow is attributed to an internal control system implemented to oversee expenditure and cash flow, which includes effective management of working capital. CONSOLIDATED STATEMENT OF FINANCIAL POSITION FOR THE YEAR ENDED DECEMBER 31 ASSETS (in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Non-current assets12,33611,063 Intangible assets3,8283,607 Property, plant and equipment429176 Right-of-use assets1,724885 Equity accounted investments3,8013,948 Other investment, including derivatives1,0001,000 Trade and other receivables1.5541.447 Current assets35,27649,801 Trade and other receivables4,1004,127 Other investment, including derivatives49910,4699 Prepayments4811,748 Cash and cash equivalents30,19633,4579 TOTAL ASSETS47,61260,864 EQUITY AND LIABILITIES(in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Equity 38.82254.045 Share capital140140 Share premium121,513121,513 Retained earnings, excluding profit (loss) for the reporting period(65,246)(53,476) Result of the period, profit (loss) for the reporting period(15,762)(11,770) Share based payment2.1611,621 Cost of Capital(4,460)(4,460) Other reserves476476 Non-current liabilities1.8531,047 Borrowings1,510747 Other financial liabilities344300 Current liabilities6,9375,772 Borrowings241138 Other financial liabilities3,2003,212 Trade and other liabilities3,4962,422 Current tax liabilities-- TOTAL EQUITY AND LIABILITIES47,61260,864 CONSOLIDATED STATEMENT OF PROFIT OR LOSS AND OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED DECEMBER 31 in € thousands20232022 restated*VarianceRevenue 2,8141,95147%Other operating income1,5924353252%Operating income4,4062,38685%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)1044%Selling, general and administrative expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating expenses(20,642)(14,024)47%Operating profit/(loss) (EBIT)(16,236)(11,638)40%Financial income86746686%Financial expenses(393)(594)-34%Profit/(loss) before taxes(15,762)(11,766)34%Income taxes-(4) PROFIT/(LOSS) FOR THE PERIOD(15,762)(11,770)34% CONSOLIDATED STATEMENT OF CHANGES IN EQUITY FOR THE YEAR ENDED DECEMBER 31 2023 (in thousands of euros) Attributable to equity holders of the CompanyTotal EquityShare capital Share premium Other reservesRetained earnings Share-based payment reserveCost of CapitalOther reservesBalance at December 31, 2021129103,6932,391(3,827)476(54,805)48,056Private Placement Via an Accelerated Bookbuild Offering514,995 (634) 14,366Equity Transaction via Transaction Warrants 62,826(1,329) 1,3292,832Share-based payments 560 560Total comprehensive income (11,770)(11,770)Balance at December 31, 2022140121,5131,622(4,460)476(65,246)54,045Share-based payments 539 539Total comprehensive income (15,762)(15,762)Balance at December 31, 2023140121,5132,161(4,460)476(81,008)38,822 CONSOLIDATED STATEMENT OF CASH FLOWS FOR THE YEAR ENDED DECEMBER 31 2023 in € thousands20232022 Restated* CASH FLOW FROM OPERATING ACTIVITIES Net result(15,762)(11,770) Adjustments to reconcile net loss to net cash provided by operating activities: Depreciation, amortisation and impairments349196 Share-based payment expense539560 Derivatives financial instruments(52)52 Interest income on deposits and current accounts-164 Net finance result(474)- Change in fair value of financial assets311- Loss on derecognition of shareholders loans-486 Equity transaction costs-29 Share of profit of equity-accounted investees, net of tax147130 Losses on disposal of PPE-16 Other non-cash adjustments(17)16 Changes in working capital: Trade and other receivables(293)(921) Other investment, including derivatives(31)4 Prepayments1,268(650) Trade and Other liabilities1,236(468) Cash generated from operations(12,779)(12,157) Interest paid527 Income Taxes paid-(349) Net cash generated from operating activities(12,726)(12,499) CASH FLOW FROM INVESTING ACTIVITIES Interest received403 Purchases of property, plant and equipment(298)(101) Purchases of Intangible assets(425)(638) Acquisition of Other Investments(0)(500) Loans made to third parties- (655) Deposits10,000(10,000) Discontinued operations Net cash provided by/(used in) investing activities9,654(11,894) CASH FLOW FROM FINANCING ACTIVITIES Reimbursements of borrowings and other financial liabilities(12)(7,376) Proceeds from borrowings and other financial liabilities44- Reimbursements of lease liabilities(222)(79) Modifications/terminations Right of Use Assets2- Proceeds from Private Placement via Accelerated Book Building- 14,337 Proceeds from Execution Transactions Warrants-2,832 Interests paid-(1,877) Net cash provided by/(used in) financing activities(188)7,838 NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS(3,261)(16,555) CASH AND CASH EQUIVALENTS at beginning of year33,45750,012 CASH AND CASH EQUIVALENTS at end of year, calculated30,19633,457* RESTATEMENT OF THE YEAR 2022 and HALF-YEAR 2023 Accounting treatment of the transactions with Qliniq Hyloris initially recognized (a) €1 million in revenue in 2022 from the divestment of HY-038, and (b) € 1 million in R&D expenses and € 0,2 million in intangible assets in H1 2023 for the purchase of HY-088. A reassessment determined that both transactions qualify as a non-monetary exchange because negotiations and valuations occurred simultaneously. Due to the development stage of the products exchanged, the fair value of neither the asset received, nor the asset given up can be reliably determined. As a result of this reassessment, the restated financials for 2022 will reverse the €1 million revenue from the divestment of HY-038. This adjustment will also affect the half-year 2023 financial statements, resulting in a reversal of €1 million in R&D expenses for HY-088. These expenses are offset against the €1 million received by Hyloris for HY-038. (See Press Release dated 14th of March 2024 on the restatement for more information) The following tables summarize the impact of the restatement on the consolidated financial statements. Consolidated statement of financial position Per 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedCurrent assets50.801-1.00049.801Trade and other receivables5.127-1.0004.127Total assets61.864-1.00060.864 Equity55.045-1.00054.045Result of the period(10.770)-1.000(11.770)Total equity and liabilities61.864-1.00060.864 Consolidated statement of profit or loss and other comprehensive income For the year ended 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedRevenues2.951-1.0001.951Gross profit2.857-1.0001.857Operating profit/(loss) (EBIT)(10.638)-1.000(11.638)Profit (loss) before taxes(10.766)-1.000(11.766)PROFIT (LOSS) FOR THE PERIOD(10.770)-1.000(11.770)TOTAL COMPREHENSIVE INCOME FOR THE PERIOD(10.770)-1.000(11.770)For the year ended 31 December 2022(in €) Impact of correction of errorAs previously reportedAdjustmentAs restatedBasic/diluted earnings/(loss) per share(0.380)(0.035)(0.435) Consolidated statement of cash flows Even though there was an actual cash inflow of EUR 1 million from the out-licensing of HY-038 and a cash outflow of EUR 1.2 million resulting from the in-licensing of HY-088, the transactions are presented in the consolidated statement of cash flows for the year ended per December 31, 2023 (i.e., EUR 200k prepaid expenses), as this most faithfully presents the substance of the transactions. There is no impact on the consolidated statement of cash flows for the year ended per December 31, 2022, as no cash inflow occurred yet. Audit Report The statutory auditor, KPMG Bedrijfsrevisoren - Réviseurs d’Entreprises, represented by Olivier Declercq, has informed us that the audit procedures were not yet completed. ONGOING LEGAL PROCEEDINGS In August 2022, AltaThera Pharmaceuticals LLC filed a complaint before the District Court for the Northern District of Illinois against Academic Pharmaceuticals Inc, Dr. Somberg and Hyloris Pharmaceuticals, for (a.o.) alleged misappropriation of AltaThera’s trade secrets and confidential information, improper inventorship, and breach of contract, which seeks (punitive) damages and termination of the agreement whereby Hyloris licenses Sotalol IV to AltaThera (the “Litigation”). Hyloris moved to dismiss the complaint for improper service of process and lack of jurisdiction. Further, in November 2022, Hyloris initiated an arbitration against AltaThera for breach of the same licensing agreement between Hyloris and AltaThera in relation to Sotalol IV, including the failure of AltaThera to use commercially reasonable efforts in selling Sotalol IV as required under the licensing agreement, which seeks damages and termination of the licensing agreement (the “Arbitration”). AltaThera responded and counter-demanded, reasserting its claims from the Litigation. At the end of August 2023, all parties agreed to stipulate to the dismissal of the Litigation and to consolidate the Litigation and the Arbitration before the American Arbitration Association (“AAA”) in New York. Hyloris contests the claims asserted by AltaThera and, based upon Hyloris’ assessment of the documents and expert reports put forward to date by AltaThera to support its claims, Hyloris is of the view that there is no convincing evidence supporting AltaThera’s claims for liability or damages. On the other hand, Hyloris believes strongly in the merits of its claims against AltaThera, and that its position is well supported by its expert reports and other documents and evidence submitted to the arbitration panel. Arbitration hearings are scheduled in April 2024 with a final decision expected by the end of H1 2024. Hyloris remains fully confident about the outcome of this litigation in its favor. Hyloris however cannot guarantee that the outcome of the litigation, even if in its favor, may not have a negative impact on future sales of Sotalol IV. About Hyloris Pharmaceuticals SA Hyloris is a specialty biopharma company focused on innovating, reinventing, and optimizing existing medications to address important healthcare needs and deliver relevant improvements for patients, healthcare professionals and payors. The Company’s development strategy primarily focuses on leveraging established regulatory pathways, such as the FDA’s 505(b)2 pathway in the U.S or equivalent regulatory frameworks in other regions which are specifically designed for pharmaceuticals for which safety and efficacy of the molecule have already been established. This approach can reduce the clinical burden required for market entry, and significantly shorten the development timelines, leading to reduced costs and risks. Hyloris has built a broad, patented portfolio of 18 reformulated and repurposed value-added medicines that have the potential to offer significant advantages over existing alternatives. Two products are currently in early phases of commercialization in collaboration with commercial partners: Sotalol IV for the treatment of atrial fibrillation, and Maxigesic® IV, a non-opioid post-operative pain treatment. In addition to its core strategic focus, the Company has 1 approved high barrier generic product launched in the U.S. and 2 high barrier generic products in development. Hyloris is based in Liège, Belgium. For more information, visit www.hyloris.com and follow-us on LinkedIn. For more information, contact Hyloris Pharmaceuticals:Stijn Van Rompay, CEOstijn.vanrompay@hyloris.com+32 (0)4 346 02 07Jean-Luc Vandebroek, CFOjean-luc.vandebroek@hyloris.com+32 (0)478 27 68 42Jessica McHarguejessica.mchargue@hyloris.com+1 919 451 4740 Disclaimer and forward-looking statements Hyloris means “high yield, lower risk”, which relates to the 505(b)(2) regulatory pathway for product approval on which the Company focuses, but in no way relates or applies to an investment in the Shares. Certain statements in this press release are “forward-looking statements.” These forward-looking statements can be identified using forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. These statements relate to future events or the Company’s future financial performance and involve known and unknown risks, uncertainties, and other factors, many of which are beyond the Company’s control, that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law. 1 https://www-aafp-org.libproxy1.nus.edu.sg/pubs/afp/issues/2010/1115/p1209.html2 IQVIA3 https://caddac.ca/about-adhd/4 https://journals-sagepub-com.libproxy1.nus.edu.sg/doi/10.1177/10600280135106995 Not adjusted for inflation6 Based on combination of different sources: population-based study, clinical based study and key opinion leaders' estimation7 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates)8 Reclassification of the loan to third-party from Operating to Investing activities in the Cash flow statement9 Reclassification of deposit from Cash and cash equivalents to Other investment including derivatives for an amount of €10 million in 202210 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates) for an amount of €120k Attachment 20240314 Full Year Results 2023 ENG

LINZESS® (Iinaclotide) 2023 U.S. net sales of $1.1 billion, an increase of 7% year-over-year, driven by EUTRx prescription demand growth of 10% year-over-year 2023 Ironwood revenue of $443 million, driven primarily by $430 million in U.S. LINZESS collaboration revenue Continues to expect topline results from the STARS Phase III study of apraglutide in patients with short bowel syndrome with intestinal failure (SBS-IF) in March of 2024 BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, today reported its fourth quarter and full year 2023 results and recent business performance. “In 2023, we made important progress toward realizing our vision to become the leading GI healthcare company in the industry,” said Tom McCourt, chief executive officer of Ironwood. “In its 11th year on market, LINZESS had another terrific year as the leading prescription treatment for adults with IBS-C or chronic idiopathic constipation, with prescription demand increasing a robust 10% year-over-year. In June of 2023, LINZESS received FDA approval for functional constipation in pediatric patients ages 6 to 17, becoming the first and only prescription therapy for this patient population. In addition, we strengthened our GI pipeline with the addition of apraglutide. We believe apraglutide has the potential to improve the standard of care for patients with short bowel syndrome dependent on parenteral support, if approved, as the only once-weekly GLP-2 therapy, and achieve $1 billion dollars in peak net sales. Looking ahead in 2024, we remain focused on maximizing LINZESS, advancing our GI pipeline and delivering sustained profits and cash flows. We are excited about the continued strong LINZESS performance and the key pipeline catalysts ahead of us, highlighted by the topline data from our STARS Phase 3 study expected in March and topline data from the ongoing Phase 2 study for CNP-104 expected in the third quarter, which we believe can propel Ironwood’s next phase of growth and create value for patients and shareholders in the years to come.” Fourth Quarter and Full Year 2023 Financial Highlights1 (in thousands, except for per share amounts) Q4 2023 Q4 2022 FY 2023 FY 2022 Total revenues $117,553 $107,199 $442,735 $410,596 Total operating expenses2 79,964 38,836 1,388,165 160,259 GAAP net income (loss)2 (1,745) 48,867 (1,031,559) 175,065 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc.2 (1,087) - (1,002,239) - GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share – basic (0.01) 0.32 (6.45) 1.13 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share – diluted (0.01) 0.27 (6.45) 0.96 Adjusted EBITDA2 39,895 68,703 (884,820) 251,755 Non-GAAP net income (loss)2 39 48,885 (973,788) 174,883 Non-GAAP net income (loss) per share – basic (0.00) 0.32 (6.27) 1.13 Non-GAAP net income (loss) per share – diluted (0.00) 0.27 (6.27) 0.96 1. Refer to the Reconciliation of GAAP Results to Non-GAAP Financial Measures table and to the Reconciliation of GAAP Net Income to Adjusted EBITDA table at the end of this press release. Refer to Non-GAAP Financial Measures for additional information. 2. Figures presented for FY 2023 include a one‐time charge of approximately $1.1 billion related to acquired in‐process research and development from the acquisition of VectivBio in the second quarter of 2023. Fourth Quarter and Full Year 2023 Corporate Highlights U.S. LINZESS Prescription Demand: Total LINZESS prescription demand in the fourth quarter of 2023 was 50 million LINZESS capsules, a 10% increase compared to the fourth quarter of 2022, per IQVIA. Total prescription demand was 191 million LINZESS capsules for the full year 2023, a 10% increase compared to the full year 2022, per IQVIA. U.S. Brand Collaboration: LINZESS U.S. net sales are provided to Ironwood by its U.S. partner, AbbVie Inc. (“AbbVie”). LINZESS U.S. net sales were $274.4 million in the fourth quarter of 2023, a 5% increase compared to $260.3 million in the fourth quarter of 2022, and $1,073.2 million for the full year 2023, a 7% increase compared to $1,002.1 million for the full year 2022. Ironwood and AbbVie share equally in U.S. brand collaboration profits. See the LINZESS U.S. Commercial Collaboration table at the end of the press release. – LINZESS commercial margin was 77% in the fourth quarter of 2023, compared to 74% in the fourth quarter of 2022. LINZESS commercial margin was 73% for the full year in each of 2023 and 2022. See the U.S. LINZESS Full Brand Collaboration table below and at the end of this press release. – Net profit for the LINZESS U.S. brand collaboration, net of commercial and research and development (“R&D”) expenses, was $202.5 million in the fourth quarter of 2023, compared to $183.8 million in the fourth quarter of 2022. Net profit for the LINZESS U.S. brand collaboration, net of commercial and R&D expenses, was $749.9 million for the full year 2023, compared to $695.7 million for the full year 2022. See U.S. LINZESS Full Brand Collaboration table below and at the end of this press release. Collaboration Revenue to Ironwood: Ironwood recorded $114.0 million in collaboration revenue in the fourth quarter of 2023 related to sales of LINZESS in the U.S., a 9% increase compared to $104.8 million for the fourth quarter of 2022. Ironwood recorded $430.5 million in collaboration revenue for the full year 2023, an 8% increase compared to $398.8 million in 2022. See U.S. LINZESS Commercial Collaboration table at the end of the press release. U.S. LINZESS Full Brand Collaboration (in thousands, except for percentages) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 LINZESS U.S. net sales as reported by AbbVie 274,356 $260,327 1,073,210 $1,002,143 AbbVie & Ironwood commercial costs, expenses and other discounts 62,903 66,879 286,045 272,757 Commercial margin 77% 74% 73% 73% AbbVie & Ironwood R&D Expenses 8,980 9,684 37,250 33,684 Total net profit on sales of LINZESS 202,473 183,764 749,915 695,702 Full brand margin 74% 71% 70% 69% In January 2024, Ironwood announced publication in The Lancet Gastroenterology & Hepatology of new linaclotide Phase III data in children and adolescents aged 6-17 years with functional constipation. The data highlighted additional efficacy endpoints from the company’s pivotal Phase III trial, which formed the basis of the June 2023 U.S. Food and Drug Administration (FDA) approval of linaclotide for the treatment of functional constipation in this population. Additional details can be found here. In October 2023, Ironwood presented new data at the 2023 North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Annual Meeting reinforcing the impact of linaclotide on functional constipation in children and adolescents ages 6-17 years-old. The data demonstrated that linaclotide reduces the need for rescue medications in this patient population and further characterized the efficacy and safety pro linaclotide as the only FDA-approved prescription therapy for this population. Additional details can be found here. Pipeline Updates Apraglutide Ironwood is advancing apraglutide, a next-generation, synthetic glucagon-like peptide-2 (“GLP-2”) analog for short bowel syndrome with intestinal failure (“SBS-IF”), a severe malabsorptive condition. Ironwood believes apraglutide has the potential to be the new standard of care for the treatment of short bowel syndrome dependent on parenteral support, also known as short bowel syndrome with intestinal failure, based on its potency and pharmacologic properties. Ironwood is conducting a Phase III clinical trial, STARS, designed to evaluate clinical benefit for both SBS-IF stoma and colon-in-continuity (“CIC”) patients with the unique convenience of weekly dosing. Topline results are expected in March of 2024. In October 2023, Ironwood presented positive final data from the company’s Phase II STARS Nutrition program during United European Gastroenterology (UEG) Week. This multicenter, open-label study of nine patients was designed to evaluate the safety, pharmacokinetics, and efficacy of apraglutide on intestinal absorption in adult patients who have SBS-IF and CIC. Additional details can be found here. Ironwood is also conducting an exploratory Phase II clinical trial, STARGAZE, to evaluate apraglutide in patients with steroid-refractory acute Graft versus Host Disease (aGvHD), a life-threatening condition that occurs when immune cells from the donor attack a recipient’s healthy cells after an allogeneic hematopoietic stem cell transplant. Enrollment is completed and data is expected for the STARGAZE Phase II clinical trial in the first quarter of 2024. CNP-104 Ironwood has a collaboration and license option agreement with COUR Pharmaceuticals Development Company, Inc. (“COUR”). This agreement grants Ironwood an option to acquire an exclusive license to research, develop, manufacture and commercialize, in the U.S., products containing CNP-104 (“CNP-104”), a tolerizing immune modifying nanoparticle, for the treatment of primary biliary cholangitis (“PBC”), a rare autoimmune disease targeting the liver. If successful, CNP-104 has the potential to be the first approved disease modifying therapy for PBC. COUR is currently conducting a clinical study with CNP-104 evaluating the safety, tolerability, pharmacodynamic effects and efficacy of CNP-104 in PBC patients, with topline data expected in the third quarter of 2024. IW-3300 Ironwood is currently advancing IW-3300, a guanylate cyclase-C agonist being developed for the potential treatment of visceral pain conditions, such as interstitial cystitis / bladder pain syndrome (“IC/BPS”) and endometriosis. Ironwood is continuing the Phase II proof of concept study in IC/BPS. Fourth Quarter and Full Year 2023 Financial Results Total Revenues. Total revenues in the fourth quarter of 2023 were $117.6 million, compared to $107.2 million in the fourth quarter of 2022. Total revenues for the full year 2023 were $442.7 million, compared to $410.6 million for the full year 2022. Total revenues in the fourth quarter of 2023 consisted of $114.0 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S. and $3.6 million in royalties and other revenue. Total revenues in the fourth quarter of 2022 consisted of $104.8 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S. and $2.4 million in royalties and other revenue. Total revenues for the full year 2023 consisted of $430.5 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S., and $12.2 million in royalties and other revenue. Total revenues for the full year 2022 consisted of $398.8 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S., and $11.8 million in royalties and other revenue. Operating Expenses. Operating expenses in the fourth quarter of 2023 were $80.0 million, compared to $38.8 million in the fourth quarter of 2022. Operating expenses for the full year 2023 were $1,388.2 million, compared to $160.3 million for the full year 2022. Operating expenses in the fourth quarter of 2023 consisted of $38.7 million in selling, general and administrative (“SG&A”) expenses, $35.7 million in R&D expenses, $5.0 million in acquired in‐process research and development as well as $0.6 million in restructuring expenses. Operating expenses in the fourth quarter of 2022 consisted of $28.4 million in SG&A expenses and $10.4 million in R&D expenses. Operating expenses for the full year 2023 consisted primarily of approximately $1.1 billion in acquired in‐process research and development relating to the acquisition of VectivBio, $158.3 million in SG&A expenses, $116.1 million in R&D expenses and $18.3 million in restructuring expenses. Operating expenses for the full year 2022 consisted primarily of $116.0 million in SG&A expenses, and $44.3 million in R&D expenses. Interest Expense and Other Financing Costs. Interest expense was $8.4 million in the fourth quarter of 2023 and $21.6 million for the full year 2023, in connection with Ironwood’s convertible senior notes and revolving credit facility. Interest expense recorded in the fourth quarter of 2023 included $7.6 million in cash expense and $0.6 million in non-cash expense. Interest expense recorded for the full year 2023 included $19.3 million in cash expense and $2.1 million in non-cash expense. Interest expense was $1.5 million in the fourth quarter of 2022 and $7.6 million for the full year 2022, in connection with Ironwood’s convertible senior notes. Interest expense recorded in the fourth quarter of 2022 included $1.1 million in cash expense and $0.4 million in non-cash expense. Interest expense recorded for the full year 2022 included $5.7 million in cash expense and $1.9 million in non-cash expense. Interest and Investment Income. Interest and investment income was $1.2 million in the fourth quarter of 2023 and $19.0 million for the full year 2023. Interest and investment income was $5.4 million in the fourth quarter of 2022 and $9.5 million for the full year 2022. Gain (Loss) on Derivatives. Ironwood recorded a loss on derivatives of an insignificant amount in the fourth quarter of 2022, as a result of the change in fair value of its note hedge warrants. For the full year 2022, Ironwood recorded a gain on derivatives of $0.2 million. Ironwood’s note hedge warrants terminated unexercised upon expiration in April 2023. Income Tax Expense. Ironwood recorded $32.1 million of income tax expense in the fourth quarter of 2023, and $83.5 million of income tax expense for the full year of 2023, the majority of which was non-cash, as Ironwood continues to utilize net operating losses to offset taxable income for federal purposes and in many states. Ironwood recorded $23.4 million of income tax expense in the fourth quarter of 2022 and $77.4 million of income tax expense for the full year of 2022, the majority of which was non-cash, as Ironwood continued to utilize net operating losses to offset taxable income for federal purposes and in many states. GAAP Net Income (Loss) Attributable to Ironwood. GAAP net loss was $1.1 million, or ($0.01) per share (basic and diluted), in the fourth quarter of 2023 compared to GAAP net income of $48.9 million, or $0.32 per share (basic) and $0.27 per share (diluted), in the fourth quarter of 2022. GAAP net loss for the full year 2023 was $1.0 billion, or ($6.45) per share (basic and diluted), compared to GAAP net income of $175.1 million, or $1.13 per share (basic) and $0.96 per share (diluted), for the full year 2022. Non-GAAP Net Income (Loss). Non-GAAP net income was an insignificant amount, or ($0.00) per share (basic and diluted), in the fourth quarter of 2023, compared to non-GAAP net income of $48.9 million, or $0.32 per share (basic) and $0.27 per share (diluted), in the fourth quarter of 2022. Non-GAAP net loss for the full year 2023 was $973.8 million, or ($6.27) per share (basic and diluted), compared to non-GAAP net income of $174.9 million, or $1.13 per share (basic) and $0.96 per share (diluted), for the full year 2022. Non-GAAP net income excludes the impact of mark-to-market adjustments on the derivatives related to Ironwood’s 2022 Convertible Notes, amortization of acquired intangible assets, restructuring expenses and acquisition-related costs, all net of tax effect. See Non-GAAP Financial Measures below. Adjusted EBITDA. Adjusted EBITDA was $39.9 million in the fourth quarter of 2023, compared to $68.7 million in the fourth quarter of 2022. For the full year 2023, adjusted EBITDA was ($884.8) million, compared to $251.8 million for the full year 2022. Adjusted EBITDA is calculated by subtracting mark-to-market adjustments on derivatives related to Ironwood’s 2022 Convertible Notes, restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs, from GAAP net income. See Non-GAAP Financial Measures below. Cash Flow Highlights. Ironwood ended 2023 with $92.2 million of cash and cash equivalents, compared to $656.2 million of cash and cash equivalents at the end of 2022. In the fourth quarter of 2023 and in the full year of 2023, Ironwood repaid $25.0 million and $100.0 million, respectively, of the outstanding principal balance on its revolving credit facility used to partially finance the VectivBio acquisition. The outstanding principal balance on the revolving credit facility was $300.0 million as of December 31, 2023. Ironwood generated $35.8 million in cash from operations in the fourth quarter of 2023, compared to $79.2 million in cash from operations in the fourth quarter of 2022. Ironwood generated $183.4 million in cash from operations for the full year 2023, compared to $273.8 million for the full year 2022. Ironwood 2024 Financial Guidance. In 2024, Ironwood continues to expect: 2024 Guidance U.S. LINZESS Net Sales Growth Low-single digits % Total Revenue $435 to $455 million Adjusted EBITDA1 >$150 million Excludes potential CNP-104 option exercise 1 Adjusted EBITDA is calculated by subtracting restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs from GAAP net income. For purposes of the 2024 guidance, Ironwood has assumed it will not incur material expenses related to business development activities in 2024 and excludes any costs associated with potential CNP-104 option exercise. Ironwood does not provide guidance on GAAP net income or a reconciliation of expected adjusted EBITDA to expected GAAP net income because, without unreasonable efforts, it is unable to predict with reasonable certainty the non-GAAP adjustments used to calculate adjusted EBITDA. These adjustments are uncertain, depend on various factors and could have a material impact on GAAP net income for the guidance period. Management believes this non-GAAP information is useful for investors, taken in conjunction with Ironwood’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to Ironwood’s operating performance. These measures are also used by management to assess the performance of the business. Investors should consider these non-GAAP measures only as a supplement to, not as a substitute for or as superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. Non-GAAP Financial Measures Ironwood presents non-GAAP net income and non-GAAP net income per share to exclude the impact, net of tax effects, of net gains and losses on derivatives related to Ironwood’s 2022 Convertible Notes that are required to be marked-to-market, amortization of acquired intangible assets, restructuring expenses, and acquisition-related costs. Non-GAAP adjustments are further detailed below: The gains and losses on the derivatives related to Ironwood’s 2022 Convertible Notes were highly variable, difficult to predict and of a size that could have a substantial impact on the company’s reported results of operations in any given period. Amortization of acquired intangible assets are non-cash expenses arising in connection with the acquisition of VectivBio and are considered to be non-recurring. Restructuring expenses are considered to be a non-recurring event as they are associated with distinct operational decisions. Included in restructuring expenses are costs associated with exit and disposal activities. Acquisition-related costs in connection with the acquisition of VectivBio are considered to be non-recurring and include direct and incremental costs associated with the acquisition and integration of VectivBio to the extent such costs were not classified as capitalizable transaction costs attributed to the cost of net assets acquired through acquisition accounting. Ironwood also presents adjusted EBITDA, a non-GAAP measure, as well as guidance on adjusted EBITDA. Adjusted EBITDA is calculated by subtracting mark-to-market adjustments on derivatives related to Ironwood’s 2022 Convertible Notes, restructuring expenses, net interest expense, income taxes, depreciation and amortization, and acquisition-related costs from GAAP net income. The adjustments are made on a similar basis as described above related to non-GAAP net income, as applicable. Management believes this non-GAAP information is useful for investors, taken in conjunction with Ironwood’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to Ironwood’s operating performance. These measures are also used by management to assess the performance of the business. Investors should consider these non-GAAP measures only as a supplement to, not as a substitute for or as superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. For a reconciliation of non-GAAP net income and non-GAAP net income per share to GAAP net income and GAAP net income per share, respectively, and for a reconciliation of adjusted EBITDA to GAAP net income, please refer to the tables at the end of this press release. Ironwood does not provide guidance on GAAP net income or a reconciliation of expected adjusted EBITDA to expected GAAP net income because, without unreasonable efforts, it is unable to predict with reasonable certainty the non-GAAP adjustments used to calculate adjusted EBITDA. These adjustments are uncertain, depend on various factors and could have a material impact on GAAP net income for the guidance period. Conference Call Information Ironwood will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, February 15, 2024 to discuss its fourth quarter and full year 2023 results and recent business activities. Individuals interested in participating in the call should dial +1 (888) 596-4144 (U.S. and Canada) or (647) 495-7514 (international) using conference ID number and event passcode 1057375. To access the webcast, please visit the Investors section of Ironwood’s website at at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required. The call will be available for replay via telephone starting at approximately 11:30 a.m. Eastern Time on February 15, 2024, running through 11:59 p.m. Eastern Time on February 29, 2024. To listen to the replay, dial (800) 770-2030 (U.S. and Canada) or (647) 362-9199 (international) using conference ID number 1057375. The archived webcast will be available on Ironwood’s website for 1 year beginning approximately one hour after the call has completed. About Ironwood Pharmaceuticals Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600® company, is a leading gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS® (linaclotide), the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). LINZESS is also approved for the treatment of functional constipation in pediatric patients ages 6-17 years-old. Ironwood is also advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for rare gastrointestinal diseases, including short bowel syndrome with intestinal failure (SBS-IF) as well as several earlier stage assets. Building upon our history of GI innovation, we keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs. Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts, and has an additional site in Basel, Switzerland. We routinely post information that may be important to investors on our website at . In addition, follow us on X and on LinkedIn. About LINZESS (Linaclotide) LINZESS® is the #1 prescribed brand in the U.S. for the treatment of adult patients with irritable bowel syndrome with constipation (“IBS-C”) or chronic idiopathic constipation (“CIC”), based on IQVIA data. LINZESS is a once-daily capsule that helps relieve the abdominal pain, constipation, and overall abdominal symptoms of bloating, discomfort and pain associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining, and incomplete evacuation associated with CIC. LINZESS relieves constipation in children and adolescents aged 6 to 17 years with functional constipation. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients, with a 72 mcg dose approved for use in CIC depending on individual patient presentation or tolerability. In children with functional constipation aged 6 to 17 years, the recommended dose is 72 mcg. LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called GC-C agonists. LINZESS contains a peptide called linaclotide that activates the GC-C receptor in the intestine. Activation of GC-C is thought to result in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established. In the United States, Ironwood and AbbVie co-develop and co-commercialize LINZESS for the treatment of adults with IBS-C or CIC. In Europe, AbbVie markets linaclotide under the brand name CONSTELLA® for the treatment of adults with moderate to severe IBS-C. In Japan, Ironwood's partner, Astellas, markets linaclotide under the brand name LINZESS for the treatment of adults with IBS-C or CIC. Ironwood also has partnered with AstraZeneca for development and commercialization of LINZESS in China, and with AbbVie for development and commercialization of linaclotide in all other territories worldwide. LINZESS Important Safety Information INDICATIONS AND USAGE LINZESS® (linaclotide) is indicated for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults and functional constipation (FC) in children and adolescents 6 to 17 years of age. It is not known if LINZESS is safe and effective in children with FC less than 6 years of age or in children with IBS-C less than 18 years of age. IMPORTANT SAFETY INFORMATION WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE LINZESS is contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Contraindications LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration. LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Warnings and Precautions LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase (GC-C) agonism, which was associated with increased mortality within the first 24 hours due to dehydration. There was no age dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. Diarrhea In adults, diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients and in <1% of 72 mcg LINZESS-treated CIC patients. In children and adolescents 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg LINZESS-treated patients in the FC double-blind placebo-controlled trial. Severe diarrhea was reported in <1% of 72 mcg LINZESS treated patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated. Common Adverse Reactions (incidence ≥2% and greater than placebo) In IBS-C or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension. In FC pediatric patients: diarrhea. Please see full Prescribing Information including Boxed Warning: LINZESS® and CONSTELLA® are registered trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved. Forward-Looking Statements This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about Ironwood’s ability to execute on its mission; Ironwood’s strategy, business, financial position and operations; Ironwood’s ability to drive growth and profitability; the commercial potential of LINZESS; our financial performance and results, and guidance and expectations related thereto; LINZESS prescription demand growth, LINZESS U.S. net sales growth, total revenue and adjusted EBITDA in 2024; the commercial potential of apraglutide, including its peak sales potential; Ironwood’s anticipation of reaching new clinical development milestones in 2024 and the timing of data related thereto, and the belief that Ironwood is positioned well for long term growth. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include those related to the effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide, apraglutide, CNP-104, IW-3300, and our product candidates; the risk of uncertainty relating to pricing and reimbursement policies in the U.S., which, if not favorable for our products, could hinder or prevent our products’ commercial success; the risk that clinical programs and studies, including for apraglutide, IW-3300 and CNP-104, may not progress or develop as anticipated, including that studies are delayed or discontinued for any reason, such as safety, tolerability, enrollment, manufacturing, economic or other reasons; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; the risk of competition or that new products may emerge that provide different or better alternatives for treatment of the conditions that our products are approved to treat; the risk that we are unable to execute on our strategy to in-license externally developed products or product candidates; the risk that we are unable to successfully partner with other companies to develop and commercialize products or product candidates; the risk that healthcare reform and other governmental and private payor initiatives may have an adverse effect upon or prevent our products’ or product candidates’ commercial success; the efficacy, safety and tolerability of linaclotide and our product candidates; the risk that the commercial and therapeutic opportunities for LINZESS or our product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for linaclotide and other product candidates, that patents for linaclotide or other products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; the risk that the development of any of our linaclotide pediatric programs, apraglutide, CNP-104 and/or IW-3300 are not successful or that any of our product candidates does not receive regulatory approval or is not successfully commercialized; outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates, including abbreviated new drug application litigation; the risk that financial and operating results may differ from our projections; developments in the intellectual property landscape; challenges from and rights of competitors or potential competitors; the risk that our planned investments do not have the anticipated effect on our company revenues; developments in accounting guidance or practice; Ironwood’s or AbbVie’s accounting practices, including reporting and settlement practices as between Ironwood and AbbVie; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; the risk that our indebtedness could adversely affect our financial condition or restrict our future operations; and the risks listed under the heading “Risk Factors” and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2022, in our Quarterly Reports on Form 10-Q for the quarters ended June 30, 2023 and September 30, 2023, and in our subsequent Securities and Exchange Commission filings. Condensed Consolidated Balance Sheets (In thousands) (unaudited) December 31, 2023 December 31, 2022 Assets Cash and cash equivalents $ 92,154 $ 656,203 Accounts receivable, net 129,122 115,458 Prepaid expenses and other current assets 12,012 7,715 Restricted cash - 1,250 Total current assets 233,288 780,626 Restricted cash, net of current portion - 485 Accounts receivable, net of current portion - 14,589 Property and equipment, net 5,585 6,288 Operating lease right-of-use assets 12,586 14,023 Intangible assets, net 3,682 - Deferred tax assets 212,324 283,661 Other assets 3,608 847 Total assets $ 471,073 $ 1,100,519 Liabilities and Stockholders’ Equity Accounts payable $ 7,830 $ 483 Accrued research and development costs 21,331 5,258 Accrued expenses and other current liabilities 44,254 16,700 Current portion of operating lease liabilities 3,126 3,065 Current portion on convertible senior notes 199,560 - Note hedge warrants - 19 Total current liabilities 276,101 25,525 Operating lease liabilities, net of current portion 14,543 16,599 Convertible senior notes, net of current portion 198,309 396,251 Revolving credit facility 300,000 - Other liabilities 28,415 9,766 Total stockholders’ equity (deficit) (346,295 ) 652,378 Total liabilities and stockholders’ equity (deficit) $ 471,073 $ 1,100,519 Condensed Consolidated Statements of Income (In thousands, except per share amounts) (unaudited) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Revenues Collaborative arrangements revenue $ 117,553 $ 107,199 $ 442,735 $ 410,596 Total revenues 117,553 107,199 442,735 410,596 Operating expenses: Research and development 35,676 10,446 116,085 44,265 Selling, general and administrative 38,667 28,390 158,314 115,994 Restructuring expenses 621 - 18,317 - Acquired in-process research and development 5,000 - 1,095,449 - Total operating expenses 79,964 38,836 1,388,165 160,259 Income (loss) from operations 37,589 68,363 (945,430 ) 250,337 Other income (expense): Interest expense and other financing costs (8,423 ) (1,526 ) (21,629 ) (7,598 ) Interest and investment income 1,194 5,446 18,971 9,501 Gain on derivatives - (18 ) 19 182 Other income (expense), net (7,229 ) 3,902 (2,639 ) 2,085 Income (loss) before income taxes 30,360 72,265 (948,069 ) 252,422 Income tax expense (32,105 ) (23,398 ) (83,490 ) (77,357 ) GAAP net income (loss) (1,745 ) 48,867 (1,031,559 ) 175,065 Less: GAAP net income (loss) attributable to noncontrolling interests (658 ) - (29,320 ) - GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. $ (1,087 ) $ 48,867 $ (1,002,239 ) $ 175,065 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share—basic $ (0.01 ) $ 0.32 $ (6.45 ) $ 1.13 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share—diluted $ (0.01 ) $ 0.27 $ (6.45 ) $ 0.96 Reconciliation of GAAP Results to Non-GAAP Financial Measures (In thousands, except per share amounts) (unaudited) A reconciliation between net income (loss) on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 GAAP net income (loss)1 $ (1,745 ) $ 48,867 $ (1,031,559 ) $ 175,065 Adjustments: Mark-to-market adjustments on the derivatives related to convertible notes, net - 18 (19 ) (182 ) Amortization of acquired intangible assets 207 - 418 - Restructuring expenses 621 - 18,317 - Acquisition-related costs 1,173 - 40,718 - Tax effect of adjustments (217 ) - (1,663 ) - Non-GAAP net income (loss)1 $ 39 $ 48,885 $ (973,788 ) $ 174,883 ____________________________________ 1 GAAP and non-GAAP net loss for twelve months ended December 31, 2023 include a one-time charge of approximately $1.1 billion related to acquired in-process research and development from the acquisition of VectivBio in the second quarter of 2023. A reconciliation between basic net income (loss) per share on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share – basic $ (0.01 ) $ 0.32 $ (6.45 ) $ 1.13 Plus: GAAP net income (loss) attributable to noncontrolling interests – basic (0.00 ) - (0.19 ) - Adjustments to GAAP net income (loss) per share (as detailed above) 0.01 - 0.37 - Non-GAAP net income (loss) per share – basic $ (0.00 ) $ 0.32 $ (6.27 ) $ 1.13 Weighted average number of common shares used to calculate net income (loss) per share — basic 156,014 153,337 155,435 154,366 A reconciliation between diluted net income (loss) per share on a GAAP basis and on a non-GAAP basis is as follows: Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 GAAP net income (loss) attributable to Ironwood Pharmaceuticals, Inc. per share – diluted $ (0.01 ) $ 0.27 $ (6.45 ) $ 0.96 Plus: GAAP net income (loss) attributable to noncontrolling interests – diluted (0.00 ) - (0.19 ) - Adjustments to GAAP net income (loss) per share (as detailed above) 0.01 - 0.37 - Non-GAAP net income (loss) per share – diluted $ (0.00 ) $ 0.27 $ (6.27 ) $ 0.96 Weighted average number of common shares used to calculate net income (loss) per share — diluted 156,014 185,188 155,435 186,312 Reconciliation of GAAP Net Income to Adjusted EBITDA (In thousands) (unaudited) A reconciliation of GAAP net income (loss) to adjusted EBITDA: Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 GAAP net income (loss)1 $ (1,745 ) $ 48,867 $ (1,031,559 ) $ 175,065 Adjustments: Mark-to-market adjustments on the derivatives related to convertible notes, net - 18 (19 ) (182 ) Restructuring expenses 621 - 18,317 - Interest expense 8,423 1,526 21,629 7,598 Interest and investment income (1,194 ) (5,446 ) (18,971 ) (9,501 ) Income tax expense 32,105 23,398 83,490 77,357 Depreciation and amortization 512 340 1,575 1,418 Acquisition-related costs 1,173 40,718 Adjusted EBITDA1 $ 39,895 $ 68,703 $ (884,820 ) $ 251,755 ____________________________________ 1 GAAP net loss and adjusted EBITDA for twelve months ended December 31, 2023 includes a one-time charge of approximately $1.1 billion related to acquired in-process research and development from the acquisition of VectivBio in the second quarter of 2023. U.S. LINZESS Commercial Collaboration1 Revenue/Expense Calculation (In thousands) (unaudited) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 LINZESS U.S. net sales as reported by AbbVie2 $ 274,356 $ 260,327 $ 1,073,210 $ 1,002,143 AbbVie & Ironwood commercial costs, expenses and other discounts3 62,903 66,879 286,045 272,757 Commercial profit on sales of LINZESS $ 211,453 $ 193,448 $ 787,165 $ 729,386 Commercial Margin4 77 % 74 % 73 % 73 % Ironwood’s share of net profit 105,727 96,724 393,583 364,693 Reimbursement for Ironwood’s commercial expenses 8,260 8,048 36,875 34,074 Ironwood’s collaborative arrangement revenue $ 113,987 $ 104,772 $ 430,458 $ 398,767 ____________________________________ 1 Ironwood collaborates with AbbVie on the development and commercialization of linaclotide in North America. Under the terms of the collaboration agreement, Ironwood receives 50% of the net profits and bears 50% of the net losses from the commercial sale of LINZESS in the U.S. The purpose of this table is to present calculations of Ironwood’s share of net profit (loss) generated from the sales of LINZESS in the U.S. and Ironwood’s collaboration revenue/expense; however, the table does not present the research and development expenses related to LINZESS in the U.S. that are shared equally between the parties under the collaboration agreement. Please refer to the table at the end of this press release for net profit for the U.S. LINZESS brand collaboration with AbbVie. 2 LINZESS net sales are recognized using AbbVie’s revenue recognition accounting policies and reporting conventions. As a result, certain rebates and discounts are classified as LINZESS U.S. commercial costs, expenses and other discounts within Ironwood’s calculation of collaborative arrangements revenue. 3 Includes certain discounts recognized and cost of goods sold incurred by AbbVie; also includes commercial costs incurred by AbbVie and Ironwood that are attributable to the cost-sharing arrangement between the parties. 4 Commercial margin is defined as commercial profit on sales of LINZESS as a percent of total LINZESS U.S. net sales. US LINZESS Full Brand Collaboration1 Revenue/Expense Calculation (In thousands) (unaudited) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 LINZESS U.S. net sales as reported by AbbVie2 $ 274,356 $ 260,327 $ 1,073,210 $ 1,002,143 AbbVie & Ironwood commercial costs, expenses and other discounts3 62,903 66,879 286,045 272,757 AbbVie & Ironwood R&D Expenses4 8,980 9,684 37,250 33,684 Total net profit on sales of LINZESS $ 202,473 $ 183,764 $ 749,915 $ 695,702 ____________________________________ 1 Ironwood collaborates with AbbVie on the development and commercialization of linaclotide in North America. Under the terms of the collaboration agreement, Ironwood receives 50% of the net profits and bears 50% of the net losses from the commercial sale of LINZESS in the U.S. The purpose of this table is to present calculations of the total net profit (loss) generated from the sales of LINZESS in the U.S., including the commercial costs and expenses and the research and development expenses related to LINZESS in the U.S. that are shared equally between the parties under the collaboration agreement. 2 LINZESS net sales are recognized using AbbVie’s revenue recognition accounting policies and reporting conventions. As a result, certain rebates and discounts are classified as LINZESS U.S. commercial costs, expenses and other discounts within Ironwood’s calculation of collaborative arrangements revenue. 3 Includes certain discounts recognized and cost of goods sold incurred by AbbVie; also includes commercial costs incurred by AbbVie and Ironwood that are attributable to the cost-sharing arrangement between the parties. 4 R&D expenses related to LINZESS in the U.S. are shared equally between Ironwood and AbbVie under the collaboration agreement. View source version on businesswire.com: Contacts Investors: Greg Martini, 617-374-5230 gmartini@ironwoodpharma.com Matt Roache, 617-621-8395 mroache@ironwoodpharma.com Media: Beth Calitri, 978-417-2031 bcalitri@ironwoodpharma.com Source: Ironwood Pharmaceuticals, Inc. View this news release online at:

CAMBRIDGE, England--( BUSINESS WIRE )--Napp Pharmaceuticals Limited, a member of the international network of Mundipharma independent associated companies, today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) has authorised rezafungin for the treatment of invasive candidiasis in adults in Great Britain (GB). 1,2 The authorisation was based on positive results from the pivotal ReSTORE Phase III clinical trial which demonstrated statistical non-inferiority for rezafungin, dosed once weekly, when compared to the current standard of care, caspofungin, dosed once daily. 2,3,4 These findings are supported by the STRIVE Phase II clinical trial and an extensive nonclinical development program. 3,4 ReSTORE, a multicentre, prospective, randomised and double-blind Phase III trial compared the efficacy and safety of intravenous rezafungin with intravenous caspofungin in eligible patients with invasive candidiasis. 2,3 The primary efficacy outcome was global response (confirmed by the Data Review Committee [DRC]) at day 14. 3 Global response was determined from clinical response, mycological response, and radiologic response (for qualifying subjects with invasive candidiasis). 2,3 Of the 187 patients in the modified intention-to-treat (mITT) population, 59.1% of patients in the rezafungin group (55/93) and 60.6% of patients in the caspofungin group (57/94) had a global response of cure at day 14 (weighted treatment difference −1.1% [95% CI −14.9, 12.7]. 2,3 Non-inferiority was to be concluded if the lower bound of the 95% confidence internal (CI) for the difference in Day 14 cure rates (rezafungin – caspofungin) was >-20%. 2 Rezafungin was generally well tolerated in clinical trials, to date very common adverse reactions include hypokalaemia, pyrexia, and diarrhoea. Common adverse reactions include anaemia, hypomagnesaemia, hypophosphataemia, hypotension, wheezing, vomiting, nausea, abdominal pain, constipation, erythema, and rash. Increased blood alkaline phosphatase, hepatic enzymes, alanine aminotransferase, aspartate aminotransferase and blood bilirubin were also common. Uncommon adverse events were hyperphosphataemia, hyponatraemia, phototoxicity, tremor and increased eosinophil count. There were spontaneous reports of urticaria (frequency not known). Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness. 2 Rezafungin may cause increased risk of phototoxicity. Eligible patients should be advised to avoid sun exposure and other sources of UV radiation without adequate protection during treatment and for 7 days after the last administration of rezafungin. 2 Invasive candidiasis , is a severe, life-threatening infection of the bloodstream and/or deep/visceral tissues. 10,11 It affects seriously ill people, especially those with a weakened immune system and the mortality rate can be 40% or more. 12,13 It can place a large burden on the healthcare system, with the potential for extended treatment regimens and long hospital stays. 14 In the last 15 years there have been no new treatments and morbidity and mortality rates remain largely the same, indicating the need for alternative treatment options. 5-9,15 Professor P. Lewis White PhD, FECMM, FRCPath, Consultant Clinical Scientist and Head of the PHW Mycology Reference Laboratory, Honorary Professor, Cardiff University Centre for Trials Research said “ Invasive candidiasis remains a difficult-to-treat disease which has a significant impact on critically ill and immunocompromised patients. With limited advances in treating this condition over the past 15 years, today’s announcement is a positive step towards supporting eligible patients and could enable the healthcare professional community an alternative way to manage these patients with invasive candidiasis using a new, once-weekly intravenous treatment option .” “ This authorisation is a culmination of years of developing an additional treatment option for eligible adult patients suffering from invasive candidiasis and underscores our commitment to supporting management of infectious diseases, ” said Dr Ben David, Medical Director for Northern Europe at Mundipharma. Rezafungin has been granted Orphan Drug Designation (ODD) in GB for the treatment of invasive candidiasis in adults. 1 The MHRA grants ODD to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 5 in 10,000 people in GB where no satisfactory method of diagnosis, prevention or treatment of the condition concerned exists, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. 16 *ENDS* About invasive candidiasis Invasive candidiasis (IC) continues to be an area of significant unmet need, especially for critically ill patients in hospitals and patients with compromised immune systems. 14 Despite a number of available treatments, the mortality rate for patients with invasive candidiasis can be 40% or more. 13,14 IC is characterised as a severe, life-threatening systemic Candida infection of the bloodstream and/or deep/visceral tissues. 17 About Rezafungin Rezafungin is a novel once-weekly echinocandin that has been developed for the treatment of invasive candidiasis in adults. 18 About Napp Napp Pharmaceuticals Limited is part of Mundipharma, a global healthcare company with a presence across Africa, Asia Pacific, Canada, Europe, Latin America, and the Middle East. Mundipharma is dedicated to bringing innovative treatments to patients in the areas of pain management, infectious disease and consumer healthcare as well as other severe and debilitating disease areas. Our guiding principles, centered around Integrity and Patient-Centricity, are at the heart of everything we do. For more information visit www.mundipharma.com Future clinical trial data A second Phase III clinical trial of rezafungin for the prevention of invasive fungal disease in patients undergoing allogeneic blood and marrow transplantation (ReSPECT trial) is currently being conducted. 18 Registered office addresses NAPP PHARMACEUTICALS LIMITED a company having its registered office at Cambridge Science Park, Milton Road, Cambridge CB4 0AB, England. MUNDIPHARMA RESEARCH LIMITED, a company having its registered office at Cambridge Science Park, Milton Road, Cambridge, CB4 0AB, England. ® REZZAYO is a Registered Trademark of Cidara Therapeutics, Inc, used under license. References 1. UK Medicines and Healthcare Products Regulatory Agency authorisation. Available at: https://www.gov.uk/government/news/rezzayo-approved-to-treat-adult-patients-with-invasive-candidiasis (last accessed February 2024) 2. REZZAYO ® Summary of Product Characteristics. 3. Thompson GR, et al. Lancet 2023;401(10370):49–59. 4. Thompson GR, et al. Lancet Infect Dis 2023; https://doi-org.libproxy1.nus.edu.sg/10.1016/S1473-3099(23)00551-0 5. Ham YY, et al. Future Microbiology 2021;16(1):27–36. 6. CANCIDAS (formerly Caspofungin MSD) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/cancidas-previously-caspofungin-msd (last accessed February 2024). 7. Vfend (voriconazole) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/vfend (last accessed February 2024). 8. Ecalta (anidulafungin) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/ecalta (last accessed February 2024). 9. Mycamine (micafungin) EPAR. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/mycamine (last accessed February 2024). 10. Pappas PG, et al. Nat Rev Dis Primers 2018;4:18026. 11. CDC. Invasive candidiasis. Available at: https://www-cdc-gov.libproxy1.nus.edu.sg/fungal/diseases/candidiasis/invasive/definition.html (last accessed February 2024). 12. Kullberg BJ, Arendrup MC. N Engl J Med 2015;373:1445–56. 13. Bassetti M, et al. Crit Care 2019;23(1):219. 14. Cortegiani A, et al. Cochrane Database Syst Rev 2016;2016:Cd004920. 15. Bassetti M, et al. J Antimicrob Chemother 2018; 73 Suppl 1: i14–i25 doi:10.1093/jac/dkx445. 16. UK Medicines and Healthcare Products Regulatory Agency, Guidance – Orphan medicinal products. Available at: https://www.gov.uk/guidance/orphan-medicinal-products-in-great-britain (last accessed February 2024). 17. Cortes JA, Corrales IF. Invasive candidiasis: Epidemiology and Risk Factors. November 2018. Available at https://www.intechopen.com/chapters/64365 (last accessed February 2024). 18. Cidara Therapeutics and Mundipharma Announce Positive Topline Results from the Global Phase 3 Pivotal ReSTORE Trial of Rezafungin for the Treatment of invasive candidiasis. Available at https://www.mundipharma.com/Cidara-Therapeutics-and-Mundipharma-Announce-Positive-Topline-Results-from-the-Global-Phase-3-Pivotal-ReSTORE-Trial-of-Rezafungin-for-the-Treatment-of-Candidemia-and-Invasive-Candidiasis (last accessed February 2024). Job code: UK-RZF-2300053 Date of preparation: February 2024