Evaluation the effect of adding Sevelamer to the standard treatment of aluminum phosphide poisoning patients, referred to Tehran's Luqman Hospital, a preliminary studyon mortalit

Start Date20 Mar 2024

Sponsor / Collaborator

Shahid Beheshti University of Medical Sciences

CTR20230498

/ CompletedPhase 1

一项在健康受试者中评价含钙的磷结合剂醋酸钙片和非含钙的磷结合剂碳酸司维拉姆片对德度司他片的药动学影响的单中心、随机、开放、三周期交叉的I期临床研究

[Translation] A single-center, randomized, open-label, three-period crossover phase I clinical study to evaluate the effects of calcium-containing phosphate binder calcium acetate tablets and non-calcium-containing phosphate binder sevelamer carbonate tablets on the pharmacokinetics of dedostat tablets in healthy subjects

主要目的：评估磷结合剂碳酸司维拉姆片和醋酸钙片对德度司他片药动学的影响。次要目的：观察受试者给予磷结合剂碳酸司维拉姆片和醋酸钙片与德度司他片的安全性。

[Translation]

Primary objective: To evaluate the effect of phosphate binders sevelamer carbonate tablets and calcium acetate tablets on the pharmacokinetics of depo-depo-depo-depo-depo-depo-depo-depo-depo-depo-de- ...

Start Date13 Jul 2023

Sponsor / Collaborator

Yiqiao Hunan Pharmaceuticals Co. Ltd.

100 Clinical Results associated with Sevelamer Carbonate

100 Translational Medicine associated with Sevelamer Carbonate

100 Patents (Medical) associated with Sevelamer Carbonate

766

Literatures (Medical) associated with Sevelamer Carbonate

07 Jan 2025·Clinical Kidney Journal

The effect of sevelamer on serum calcification propensity in patients with chronic kidney disease: the results of a multicentre, double-blind, placebo-controlled, randomized clinical trial

Article

Author: El Esper, Najeh ; Kamel, Said ; Pluquet, Maxime ; Ureña-Torres, Pablo ; Laville, Solène M ; Liabeuf, Sophie ; Choukroun, Gabriel ; Brazier, François

ABSTRACTBackgroundThe serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialysed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD).MethodsThe FGF23 Reduction: Efficacy of a New phosphate binder in CHronic kidney disease (FRENCH) trial was a multicentre, double-blind, placebo-controlled, randomized trial of sevelamer carbonate in participants with stage 3b/4 CKD. In this subanalysis of the FRENCH data, T50 and other laboratory variables (including fetuin-A and ionized and total magnesium) were measured centrally at baseline and after 12 weeks of treatment.ResultsA total of 96 patients were screened and 78 (55 men and 23 women) met the inclusion criteria and were randomized to receive placebo (n = 39) or sevelamer carbonate (n = 39). The median patient age was 66 years [interquartile range (IQR) 56–72], the median eGFR was 25 ml/min/1.73 m2 (IQR 21–30) and the mean T50 was 335 minutes (standard deviation 82). In a linear regression model, T50 was independently associated with serum ionized magnesium, fetuin-A and bicarbonate levels and inversely associated with phosphate concentration. The within-group changes in the mean T50 between week 0 and week 12 were not significant in the sevelamer group or the placebo group {4.6 minutes [95% confidence interval (CI) −13.6–22.8; P = .61] and 7.8 minutes [95% CI −16.4–32.1; P = .51], respectively}. Furthermore, we did not observe significant changes in fetuin-A and magnesium levels.ConclusionA 12-week course of the non-calcium-containing phosphate binder sevelamer carbonate was not associated with a significant change in T50 in patients with stage 3b/4 CKD. Phosphate binders might not be an effective strategy for modifying serum calcification propensity in non-dialysis-dependent patients with CKD.

02 Jan 2025·Expert Opinion on Pharmacotherapy

Update on current and emerging treatment paradigms for hyperphosphatemia in chronic kidney disease

Review

Author: Salera, Davide ; Locatelli, Francesco ; Bellasi, Antonio ; Del Vecchio, Lucia

INTRODUCTIONHyperphosphatemia in advanced CKD often accompanies high PTH and FGF23 levels, impaired bone mineralization, ectopic calcifications, and increased cardiovascular risks. Novel treatments are now available to lower serum phosphorus effectively. However, safety, tolerability, and patient adherence must be evaluated to determine the best therapeutic option for hyperphosphatemia.AREAS COVEREDThis review examines available treatment strategies for hyperphosphatemia in CKD patients and new emerging treatments, emphasizing the latest inhibitors of active phosphate absorption.EXPERT OPINIONDespite the numerous compounds available, managing hyperphosphatemia in CKD remains challenging. While many phosphate binders exist, they often have limitations and side effects. Aluminum carries significant toxicity risks. Calcium-based binders are effective but can cause hypercalcemia and vascular calcification. Lanthanum is absorbed in the gut, but its long-term tissue deposition appears clinically irrelevant. Sevelamer reduces vascular calcification but has inconclusive data and gastrointestinal side effects. Iron-based binders are effective but may cause gastrointestinal discomfort and lack long-term outcome data. New inhibitors of intestinal phosphate absorption show promise with low pill burden but need more clinical validation. Although these newer compounds might eventually improve phosphate management in CKD patients, enhancing adherence and reducing pill burden, future studies are required to elucidate the best treatment for hyperphosphatemia.

01 Jan 2025·Hemodialysis International

Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: A systematic review and meta‐analysis

Review

Author: Georgopoulos, Christos ; Dounousi, Evangelia ; Duni, Anila ; Gouva, Charikleia ; Kitsos, Athanasios ; Stamellou, Eleni

AbstractIntroductionPhosphate binders are commonly used in patients receiving kidney replacement therapy (KRT), aiming to reduce and maintain serum phosphorus. Chronic kidney disease‐mineral and bone disorder has been linked to reduced lifespan and worsened quality of life. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving KRT.MethodsThe data sources examined were MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with a search deadline of October 2023. We examined randomized controlled trials that compared sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving KRT. We performed a meta‐analysis combining the data from trials, using R‐studio.FindingsInclusion criteria were met by five randomized trials. There was no statistically significant difference in the reduction of serum phosphorus between the two groups (MD: −0.07 mmol/L, 95% CI‐random effects: −0.15 to 0.02). In the same line, a non‐statistically significant difference was observed in serum i‐PTH reduction between the two drugs (MD = −1.53 mg/dL, 95% CI = (−4.45, 1.4), p = 0.26, random effects model). No statistically significant difference was observed in all adverse events between the two groups (odds ratio: 1.11, 95% CI: 0.65–1.88, random effects model). Further analysis of gastrointestinal adverse events revealed that sevelamer carbonate increases gastrointestinal adverse events by up to 60% (odds ratio: 1.60, 95% CI: 1.31–1.97, common (fixed) effect model).DiscussionThis meta‐analysis of randomized trials showed that both drugs, sucroferric oxyhydroxide and sevelamer equally and effectively controlled serum phosphorus levels, whereas sucroferric oxyhydroxide revealed a better profile in terms of gastrointestinal adverse events. Sucroferric oxyhydroxide is a valuable option for patients receiving KRT when sevelamer carbonate is more difficult to tolerate.

News (Medical) associated with Sevelamer Carbonate

14 Oct 2024

·www.globenewswire.com

EUROAPI completes the financing of its FOCUS-27 plan and moves forward with its execution

€451M Revolving Credit Facility refinanced with a maturity extended to February 2029 Issuance of a €200M Perpetual Deeply Subordinated Hybrid Bond subscribed by Sanofi €54M product capacity reservation for five products and further amendments to the global Manufacturing and Supply Agreement (MSA) agreed with Sanofi “The completion of the financing is an instrumental step in the execution of EUROAPI’s strategic roadmap” said Ludwig de Mot, Chief Executive Officer. “Combined with further developments in our commercial relationship with Sanofi, it opens a new chapter for our company and all its stakeholders.” 10 October 2024 - EUROAPI announces today that it has completed and secured the financing of its FOCUS-27 strategic plan and agreed with Sanofi to further amend the Manufacturing and Supply Agreement signed in 2021. €451M Revolving Credit Facility refinanced with a maturity extended to February 2029 EUROAPI and its banking syndicate1 have agreed on a new secured €451 million Revolving Credit Facility (RCF), refinancing the existing revolving facility with a maturity in February 2029. Loans borrowed under the RCF will bear interest at an EURIBOR-indexed floating rate, plus an applicable margin2, as a function of EUROAPI’s Net Leverage Ratio, defined as Total Net Debt to Consolidated Core EBITDA3. The RCF will be subject to a covenant stipulating that the Net Leverage Ratio may not exceed 4.00x starting 30 June 2027 and a €50 million liquidity covenant applicable from signing until maturity. €200M Perpetual Deeply Subordinated Hybrid Bond subscribed by Sanofi Sanofi confirmed its support in the execution of the FOCUS-27 plan through an investment of €200 million in a Perpetual Deeply Subordinated Hybrid Bond. This non-dilutive instrument, which will be classified as “Equity” in EUROAPI’s consolidated financial statements, provides EUROAPI with additional financial flexibility to deliver its FOCUS-27 plan. On any interest payment date, EUROAPI may decide to defer and capitalize the interest payment, subject to certain conditions, including the absence of dividend payment or share repurchases. The hybrid bond will carry a 8.113% coupon until the first reset date, scheduled for February 2029. The closing of the revised RCF and the Perpetual Deeply Subordinated Hybrid Bond is expected before the end of October 2024 and will end the company’s collaboration with the mandataire ad hoc appointed in June 2024. €54M minimum available capacity reservation for five products agreed with Sanofi To support the implementation of FOCUS-27, Sanofi has agreed to reserve a minimum available capacity for five selected products manufactured by EUROAPI. Sanofi will pay €54 million, of which €18 million in H2 2024, and €36 million in 2025. These capacity reservations will secure revenue and increase the five products' overall performance4. In addition to the capacity reservation, Sanofi and EUROAPI have agreed on further amendments to the Global Manufacturing and Supply Agreement (MSA) signed in 2021, including secured volumes for Sevelamer, which will provide further visibility to Haverhill’s activity in the context of its divestment. These amendments, including the capacity reservation fees, are Regulated Agreements pursuant to the French Commercial Code. Details are available on EUROAPI’s website. EUROAPI is focused on reinventing active ingredient solutions to sustainably meet customers’ and patients’ needs around the world. We are a leading player in active pharmaceutical ingredients with approximately 200 products in our portfolio, offering a large span of technologies while developing innovative molecules through our Contract Development and Manufacturing Organization (CDMO) activities. Taking action for health by enabling access to essential therapies inspires our 3,650 people every day. With strong research and development capabilities and six manufacturing sites, all located in Europe, EUROAPI ensures API manufacturing of the highest quality to supply customers in more than 80 countries. EUROAPI is listed on Euronext Paris; ISIN: FR0014008VX5; ticker: EAPI). Find out more at www.euroapi.com and follow us on LinkedIn. 1 BNP Paribas, Bank of America, JP Morgan, Crédit Agricole CIB, Société Générale, Deutsche Bank and Natixis 2 The margin will vary from 1.35% to 2.10% 3 Without taking into account the effects of IFRS 16 4 The €54 million capacity reservation is a financial consideration received (paid in H2 2024 and 2025) and will be recognized as revenue once the products are delivered as defined in the contract with Sanofi, mostly after 2027 The content above comes from the network. if any infringement, please contact us to modify.

Financial Statement

31 Jul 2024

·www.globenewswire.com

Ardelyx Announces Publication of Two Plain Language Summaries from XPHOZAH® (tenapanor) Clinical Trials in Current Medical Research and Opinion

WALTHAM, Mass., July 31, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced the publication of plain language summaries of results from two clinical trials on XPHOZAH® (tenapanor), NORMALIZE and OPTIMIZE, in Current Medical Research and Opinion. The plain language summaries were developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and caregivers, better understand some of the safety and efficacy data related to XPHOZAH. XPHOZAH, the first and only phosphate absorption inhibitor (PAI), is approved by the U.S. Food and Drug Administration to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH offers a different mechanism of action, blocking phosphate absorption at the primary pathway and is administered as a single tablet taken twice daily. “We are proud to provide the clinical trials results for both the NORMALIZE and OPTIMIZE studies to patients in a format that is both useful and relevant to their needs. Plain language summaries, like these, help patients and their caregivers better understand their options and the potential impact XPHOZAH may have on lowering their serum phosphorus levels,” said Laura Williams, MD MPH, chief medical officer of Ardelyx. “Our entire Ardelyx team would like to express our gratitude to the patients who participated in these clinical trials, whose contributions are now helping other patients better understand the complications associated with elevated serum phosphorus and this new treatment option. We would also like to recognize the study authors who worked with our partners in the patient advocacy community to ensure that these plain language summaries could be made available to our patients.” Current Medical Research and Opinion is an international journal that publishes research focused on new and existing drugs and therapies, best practices in patient care, developments in diagnostic medicine and medical technology, and innovations in medical and scientific publishing. The first article, titled “Tenapanor improves long-term control of high phosphate concentrations in the blood in patients receiving maintenance dialysis: a plain language summary of the NORMALIZE study,” describes results from the NORMALIZE study, is available online and can be found here. The second article, titled “Effectiveness of tenapanor for treating hyperphosphatemia in patients receiving dialysis: a plain language summary of the OPTIMIZE study” provides a review of the OPTIMIZE study, is available online and can be found here. Both articles are summaries of data originally published in Kidney360. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About NORMALIZE Patients completing the Phase 3 PHREEDOM trial from both the XPHOZAH arm and the sevelamer safety control arm had the option to participate in NORMALIZE, an open-label 18-month extension study. Patients entering the study from the XPHOZAH arm with serum phosphate levels in the normal range were followed with no medication changes. Patients entering the study from the XPHOZAH arm with serum phosphate greater than 4.5 mg/dL had sevelamer tablets added incrementally to achieve normal serum phosphate levels. Patients entering the study from the sevelamer safety control arm had XPHOZAH tablets added to their treatment regimen while reducing sevelamer tablets based on their serum phosphate value to achieve normal serum phosphate levels. The primary objective of the study was to evaluate the ability of XPHOZAH alone or in combination with sevelamer to achieve serum phosphate levels within the normal range (2.5 to 4.5 mg/dL) in patients with CKD on maintenance dialysis whose serum phosphate levels were greater than 6.0 mg/dL at baseline. About OPTIMIZEOPTIMIZE was a randomized, open label study, which included 330 patients with chronic kidney disease (CKD) on dialysis with hyperphosphatemia. The study was designed to evaluate different methods of initiating XPHOZAH to optimize phosphorus management in both binder-naïve and binder-treated patients. The objective was to evaluate the ability of XPHOZAH, with its novel blocking mechanism, administered as core therapy for the treatment of hyperphosphatemia in adult patients with chronic kidney disease (CKD) on dialysis, alone or in combination with phosphate binders, to achieve target serum phosphorus (s-P) levels ≤5.5 mg/dL. The study enrolled patients with s-P >5.5 and ≤10.0 mg/dL during stable phosphate binder treatment which were randomized in a 1:1 ratio to two different treatment cohorts, as well as patients who were phosphate binder naïve with s-P >4.5 and ≤10.0 mg/dL in a third cohort. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONSXPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com

Clinical ResultPhase 3Drug ApprovalLicense out/inClinical Study

30 Jul 2024

·www.globenewswire.com

H1 2024 Results - Focus-27 strategic plan on track with timely execution of the operational roadmap

Press ReleaseParis, 30th July 2024 Net Sales down 9.6% year-on-year – Core EBITDA margin at 10.6%Accelerated commercial momentum with clients other than Sanofi, with Net Sales up 2.9%, excluding the Brindisi site, where production was temporarily suspendedEnhanced effectiveness across the entire organization, with sizeable improvements in industrial efficiencies€10 million Free Cash Flow before financing, driven by strengthened financial disciplineFY 2024 guidance confirmed " Our H1 actions set the foundations of our more agile, streamlined, and value-creating model. Over the past months, with the entire organization's support, we have made significant progress in deploying the four strategic pillars of our operational roadmap. Thanks to a comprehensive mitigation plan, we will resume shipment and production in Brindisi in the coming weeks." said Ludwig de Mot, Chief Executive Officer of EUROAPI. "Confident in the collective success of our plan, we are in advanced discussions with our stakeholders to finalize the financing of FOCUS-27 in the coming weeks, which will pave the way for long-term profitable growth.” €448.7 million in Net Sales, down by 9.6%1, shaped by the strong decrease in volumes from Sanofi and the suspension of production in Brindisi, which overshadowed the positive momentum of sales to clients other than Sanofi Brindisi GMP license reactivated mid-July; shipments and production to restart gradually during Q3 2024 Signature of a major CMO commercial phase contract with a global animal health company and a development and manufacturing agreement with Priothera, a biotechnology company specializing in oncology €47.6 million Core EBITDA, with a 10.6% Core EBITDA margin, down from 12.6% in H1 2023. Price increases and product mix, industrial efficiencies, and the impact of the revised commercial contractual clauses with Sanofi over the period partially offset the unfavorable fixed-cost absorption. €(1.4) million EBITDA, including €47.2 million exceptional costs related to the implementation of FOCUS-27. €(170.2) million Net Debt compared to €(171.0) million at the end of December 2023, with €10.0 million Free Cash Flow before financing, compared to €(111.2) million for the same period last year, driven notably by Controlled CAPEX (€61.3 million, of which 56% dedicated to growth) Improved Operating Working Capital thanks to a rigorous inventory reduction program and better cash collection €(34.8) million Net income, compared to €62.8 million in H1 2023 H1-2024 Key figures (in € millions)H1-2024H1-2023Net Sales448.7496.6Year-on-year change in %-9.6%+2.6%Gross profit98.097.0Gross Profit Margin21.8%19.5%EBITDA(1.4)52.1Core EBITDA47.662.5Core EBITDA Margin10.6%12.6%Net Income(34.8)62.8Basic EPS (in euros)(0.37)0.67 2024 outlook confirmed Between 8% and 11% decrease in 2024 Net Sales compared to 2023 on a comparable basis, with a second-half performance slightly exceeding that of the first half due to a phasing impact in CDMO. Core EBITDA margin objective expected between 4% and 7%. The positive impact in H1 of the revised contractual clauses with Sanofi will be lower in the second half. FOCUS-27 plan in action The execution of FOCUS-27 is on track, with several initiatives launched during the first half, and the discussions with the Revolving Credit Facility banking syndicate to finalize the financing announced on June 26, 2024, are in the advanced stage. Streamlined value-added portfolio List of the discontinued 13 APIs communicated to our clients; phase-out roadmap almost completedAccelerated momentum in Opiates, prompted by improving competitive positions Focused CDMO offer Solid and qualitative new late-stage projects with 3 marketed small molecules for large and mid-size pharma and food companies (including GMP intermediates). Increasing momentum in large molecules, with 5 early-stage projects in H1, mainly from large pharma companies, including 4 promising new oligonucleotides and 1 peptide-PMO conjugate project. Rationalized industrial footprint Ramp down of workshops initiated in Frankfurt (9 APIs to be discontinued), and Vertolaye (2 APIs to be discontinued)Inventory reduction program on track Haverhill divestment process well advanced; completion expected in 2025 Organizational transformation Headcount reduction plan initiated in Haverhill following the decrease in volumes of SevelamerContinued enhancement of the management teams across the group, including the reorganization of the Executive leadership team. H1-2024 Net Sales EUROAPI H1-2024 Net Sales reached €448.7 million, -9.6% versus H1 2023 and -9.3% at Constant Exchange Rates. Net sales per type of activity (in € millions)H1H1-2023ChangeAPI Solutions – Other clients168.6169.8-0.7%API Solutions – Sanofi163.7192.7-15.0%API Solutions332.4362.4-8.3%CDMO – Other clients72.382.7-12.7%CDMO – Sanofi44.151.4-14.2%CDMO116.4134.2-13.3%Net sales448.7496.6-9.6%Total Net Sales – Sanofi207.8244.1-14.9%Total Net Sales – Other clients 240.9252.5-4.6% API Solutions API Solutions' net sales decreased by 8.3% to €332.4 million. Sales to Sanofi decreased by 15.0% due to strong volume decrease, notably in Sevelamer, produced in Haverhill, and the suspension of production in Brindisi. H1 net sales include €29 million related to the revision of the historical MSA contractual clauses agreed with Sanofi in February 20242, primarily Buserelin’s3 stock clearance. Sales to Other Clients decreased by 0.7%, impacted by the temporary suspension of API production in Brindisi. Excluding Brindisi’s site, net sales would have grown 3.4%, driven by the cross-selling strategy (representing 9.1% of H1 API Solutions sales to Other Clients) and an increased customer base (22 new clients added in H1). CDMO CDMO sales decreased by 13.3% to €116.4 million. Sales to Sanofi decreased by 14.2% on the back of a strong H1 2023 performance, which was boosted by stock replenishment of Pristinamycin, an anti-infective produced exclusively for Sanofi in Elbeuf. H1 2024 sales benefited from the ramp-up of a commercial phase contract in Large Molecules.Sales to Other Clients decreased by 12.7% due to the temporary suspension of production in Brindisi, which affected a commercial phase contract. H1 2024 performance was also penalized by the downsizing of two large historical commercial phase contracts (approximately -10 M€), which more than offset the increase in revenue from new contracts. Excluding the impact of Brindisi, total CDMO sales to clients other than Sanofi would have grown by 1.8%, with increased revenues from early-stage projects. Throughout the semester, 14 new CDMO contracts were signed, and eight projects were completed, including two in late stage with Sanofi, and two projects were put on hold. (Number of CDMO projects)Phase 1 and earlierPhase 2Phase 3Commercial PhaseTotalLarge molecules742417Highly potent molecules1 12Biochemistry molecules derived from fermentation2 68Complex chemical synthesis molecules9772346Total191193473 Net Sales per type of molecule (in € million)H1-2024H1-2023ChangeLarge molecules58.835.0+67.9%Highly potent molecules47.143.7+7.8%Biochemistry molecules derived from fermentation43.785.5-48.8%Complex chemical synthesis molecules299.1332.4-10.0%Net Sales448.7496.6-9.6% Large molecules increased by 67.9% to €58.8 million, driven by the stock clearance of Buserelin, and the ramp-up of a commercial phase contract in Large Molecules with Sanofi. Highly potent molecules were up 7.8% to €47.1 million on the back of a low comparison base in H1 2023, which was impacted by the suspension of Prostaglandins’ production.Biochemistry molecules derived from fermentation decreased 48.8% to €43.7 million. While H1 2023 performance was boosted by stock replenishment of Pristinamycin, H1 2024 was impacted by the temporary suspension of API production in Brindisi. Complex chemical synthesis molecules decreased by 10.0% to €299.1 million, mainly impacted by the decreasing volume demand from Sanofi. Financial performance (in € million)H1-2024H1-2023Net Sales448.7496.6Other revenues2.21.9Gross profit98.097.0Gross Profit Margin21.8%19.5%EBITDA(1.4)52.1Non-recurring costs49.010.4Core EBITDA47.662.5Core EBITDA Margin10.6%12.6%Operating Income(33.4)16.0Finance revenues/costs(8.1)(3.3)Income before tax(41.5)12.6Income tax expense6.750.1Net income/(loss)(34.8)62.8EPS (in euros)(0.37)0.67Average number of shares outstanding (in millions)94.393.9Fully diluted EPS (in euros)(0.37)0.66Average number of shares after dilution (in millions)95.995.5 Gross profit was €98.0 million, compared to €97.0 million in H1 2023, with the gross profit margin up 231 basis points year-on-year to 21.8%. The exceptional impact of Buserelin’s stock clearance, positive price and mix effect, lower energy and raw materials prices, and improved industrial performance more than offset unfavorable fixed-cost absorption as we sold in H1 24 products manufactured at the peak level of the past 18 months inflation cycle. Core EBITDA amounted to €47.6 million, down 23.8% compared to €62.5 million in H1 2023. The core EBITDA margin was 10.6%, compared to 12.6% in H1 2023. The increase in OPEX was mostly driven by the company's transformation and reorganization. EBITDA was €(1.4) million compared to €52.1 million in H1 2023. The 49.0 million non-recurring costs include €47.2 million in exceptional items4, of which €33.8 million of idle costs5 linked to the execution of FOCUS-27, including the ramp-down of two workshops in Frankfurt started in H1 2024 and reduced inventories in Vertolaye €9.0 million of internal and external costs related to the transformation of the company €4.4 million of employee-related expenses, including redundancy plans. Key components of the change in Core EBITDA marginH124/H123 in percentage points (rounded figures)H1 2023 Core EBITDA margin12.6%Volume-0.0 ptsPrice and Mix+3.0 ptsImpact of Buserelin’s stock clearance+2.1 ptsIndustrial performance+2.4 ptsEnergy and Raw Materials+1.2 ptsUnfavorable fixed cost absorption-5.5 ptsOther Gross Margin impacts -1.9 ptsOPEX -2.9 ptsBrindisi site, including the impact of the suspension of production-0.3 ptsH1 2024 Core EBITDA margin10.6% Operating Income was €(33.4) million compared to €16.0 million in H1 2023. Financial income was €(8.1) million, compared with €(3.3) million in H1 2023, due notably to the increase in interest rates and the full drawdown of the RCF. Income before tax was €(41.5) million6. Net income was €(34.8) million in H1 2024. Net Debt Position and Cash Flow (in € million)30 June 2024Net cash/(Debt) position – December 2023(171.0)Cash Flow from Operating activities71.2Of which change in Working Capital66.1 (Increase)/decrease in inventories 4.1 (Increase)/decrease in trade receivables 40.0 Increase/(decrease) in trade payables (16.2) Other current assets and liabilities 38.3Cash Flow from Investing Activities(61.3)of which CAPEX(61.3)Cash Flow from Financing activities(8.3)Exchange rate((0.9)Net Cash/(Debt) position – June 2024(170.2) The decrease in Net Debt position, €(170.2) million compared to a €(171.0) million at the end of December 2023, was notably driven by Working Capital, including the improvement in inventories. Improved cash collection drove the change in Trade receivables, with DSO down to 53 compared to 56 in December 2023 and 70 in H1 2023. Other current assets and liabilities include a €27 million variation in VAT tax reimbursement. Capex reached €(61.3) million (13.7% of Net Sales), of which 56% were dedicated to growth projects, including increased capacities for Peptides and Oligonucleotides, Vitamin B12, and Prostaglandins. Free Cash Flow before financing activities was €10.0 million, compared to €(111.2) million at the end of June 2023.7 (in € million)30 June 202431 December 2023Bank Cash Balances282.834.5Revolving Credit Facilities(453.0)8(205.5)Net Debt Position(170.2)(171.0) Net Debt to Core EBITDA restated for IFRS 16 was 2.38x, below the RCF covenant of 4.0x.ESG Roadmap EUROAPI ESG roadmap is on track to achieve its 2030 goals and has recently achieved: 100% of its sites certified ISO14001 (environment management) and ISO50001 (energy management). CDP score B, which indicates that the group is addressing the environmental impacts of its business and ensures good environmental management. Main H1 2024 events On January 25, 2024, EUROAPI announced that it had initiated a pivotal collaboration with SpiroChem, a leading Contract Research Organization (CRO).On March 14, 2024, EUROAPI announced the pause of API production at the Brindisi site in Italy after identifying quality control deficiencies and decided to suspend its full-year 2024 guidance.On May 23, 2024, EUROAPI announced a Contract Manufacturing Organization (CMO) agreement with a global animal health company to supply key veterinary product. The total contract value is expected to range between €130 and 150 million over 2025-2029.On June 6, 2024, EUROAPI received official notification from the European Commission that it had been selected as one of the 13 companies eligible to share up to EUR 1 billion in total public funding under the Important Project of Common European Interest (IPCEI) dedicated to the pharmaceutical sector.On June 18, 2024, EUROAPI announced the implementation of a 5-year development and manufacturing agreement with Priothera, a biotechnology company specializing in treating hematological malignancies and improving CAR-T cell therapies.On June 26, 2024, EUROAPI detailed the FOCUS-27 strategy and announced its target to generate €75 million to €80 million annual run-rate incremental Core EBITDA by the end of 2027. More detail on EUROAPI’s website: EUROAPI is moving ahead with its FOCUS-27 plan, setting the foundations for future profitable growth | EUROAPIannounced that the Brindisi site will progressively resume shipments and production during Q3 2024. Glossary and definition of non-GAAP indicators EBITDA and Core EBITDA EBITDA corresponds to operating income (loss) restated for depreciation and amortization and net impairment of intangible assets and property, plant and equipment.Core EBITDA thus corresponds to EBITDA restated for restructuring costs and similar items (excluding depreciation and write-downs), allocations net of reversals of unutilized provisions for environmental risks, and other items not representative of the Group’s current operating performance or related to the effects of acquisitions or disposals. Cash Flow before Financing activities Cash Flow before Financing activities corresponds to the sum of Cash Flow from Operating Activities and Cash Flow from Investing Activities as presented in the consolidated statement of Cash Flow. Months on Hand (MOH) Net Inventory value at the of the period divided by Net Sales New clients Clients representing at least €50 thousands of net sales on the year. Cross Selling Selling a different product to an existing client that is already buying one or several products from EUROAPI. Early-stage and Late-stage projects Early-stage: pre-clinical, phase 1, and phase 2Late-stage: phase3, in validation, and commercial Presentation of H1-2024 results An analysts’ conference call will be held by EUROAPI’s management tomorrow (31 July 2024) at 8:30 a.m. CET via an audio webcast (live and replay), and the results presentation will be available on the corporate website 2024 Half year results | EUROAPI Financial agenda (all dates to be confirmed) 11 February 2025: FY 2024 Results21 May 2025: 2025 AGM29 July 2025: H1 2025 results About EUROAPIEUROAPI is focused on reinventing active ingredient solutions to sustainably meet customers’ and patients’ needs around the world. We are a leading player in active pharmaceutical ingredients with approximately 200 products in our portfolio, offering a large span of technologies while developing innovative molecules through our Contract Development and Manufacturing Organization (CDMO) activities. Taking action for health by enabling access to essential therapies inspires our 3,650 people every day. With strong research and development capabilities and six manufacturing sites, all located in Europe, EUROAPI ensures API manufacturing of the highest quality to supply customers in more than 80 countries. EUROAPI is listed on Euronext Paris; ISIN: FR0014008VX5; ticker: EAPI). Find out more at www.euroapi.com and follow us on LinkedIn. Media Relations contact:Laurence BollackTel.: +33 (0)6 81 86 80 19mr@euroapi.com Investor Relations contacts:Sophie Palliez-CapianTel.: +33 (0)6 87 89 33 51Sophie.palliez@euroapi.com Camille RicotierTel: +33 (0)6 43 29 93 79Camille.ricotier@euroapi.com Forward-Looking StatementsCertain information contained in this press release is forward looking and not historical data. These forward-looking statements are based on opinions, projections and current assumptions including, but not limited to, assumptions concerning the Group’s current and future strategy, financial and non-financial future results and the environment in which the Group operates, as well as events, operations, future services or product development and potential. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Forward looking statements and information do not constitute guarantees of future performances, and are subject to known or unknown risks, uncertainties and other factors, a large number of which are difficult to predict and generally outside the control of the Group, which could cause actual results, performances or achievements, or the results of the sector or other events, to differ materially from those described or suggested by these forward-looking statements. These risks and uncertainties include those that are indicated and detailed in Chapter 3 “Risk factors” of the Universal Registration Document filed with the French Financial Markets Authority (Autorité des marchés financiers, AMF) on April 5, 2024. These forward-looking statements are given only as of the date of this press release and the Group expressly declines any obligation or commitment to publish updates or corrections of the forward-looking statements included in this press release in order to reflect any change affecting the forecasts or events, conditions or circumstances on which these forward-looking statements are based. Appendix Consolidated Income Statement (in € millions)30-Jun-2430-Jun-23Net sales448.7 496.6 Other revenues2.2 1.9 Cost of sales(352.9)(401.4)Gross profit98.0 97.0 Selling and distribution expenses(18.7)(21.3)Research and development expenses(13.9)(13.3)Administrative and general expenses(46.6)(42.8)Other operating income1.3 0.7 Impairment of assets(3.9) Restructuring costs and similar items(49.7)(4.3)Operating income(33.4) 16.0 Financial expenses(11.2)(5.3)Financial income3.1 1.9 Income/(loss) before tax(41.5) 12.6 Income tax expense6.7 50.1 Net income/(loss)(34.8) 62.8 Number of shares outstandings94.393.9EPS(0.37)0.67Diluted number of shares 95.995.5EPS diluted(0.37)0.66 Consolidated Balance Sheet (in € millions)30-Jun-2431-Dec-23Goodwill4.6 4.6 Property, plant and equipment469.0 468.9Right-of-use assets35.2 37.2Intangible assets38.9 34.2Other non-current assets6.7 9.0Deferred tax assets85.7 79.2Non-current assets640.2633.1Inventories638.7 644.8Trade receivables176.7 216.3Other current assets57.5 83.7Cash and cash equivalents282.8 34.5Current assets1,155.8979.3Total assets1,795.91,612.4(in € millions)30-Jun-2431-Dec-23Equity attributable to owners of the parent889.5927.7Total equity889.5927.7Non-current lease liabilities14.515.5Provisions155.3158.6Other non-current liabilities0.00.0Deferred tax liabilities0.81.6Non-current liabilities170.6175.7Trade payables143.6159.6Other current liabilities135.1139.3Current lease liabilities4.34.6Short-term debt and other financial liabilities452.8205.4Current liabilities735.9508.9Total equity and liabilities1,795.91,612.4 Consolidated Statements of Cash Flow (in € millions)30-Jun-2430-Jun-23Net income / (loss)(34.8)(62.8)Depreciation & amortization 32.0 36.1 Net change in current & deferred taxes(6.7)(50.1)Other profit or loss items with no cash effect and reclass of interest 14.7 8.2 Operating cash flow before changes in working capital 5.1 56.9 (Increase)/decrease in inventories 4.1 (66.0)(Increase)/decrease in trade receivables 40.0 30.1 Increase/(decrease) in trade payables(16.2)(49.0)Net change in other current assets and other current liabilities 38.3 (10.3)Net cash provided by operating activities 71.2 (38.2) Acquisitions of property, plant and equipment and intangible assets(61.3)(73.1)Acquisition of shares on consolidated entities, net of cash acquired - Sales/Acquisitions to/from Group entities 0.0 - Net cash (used in) investing activities(61.3)(73.1)Capital increases - - Repayment of lease liabilities(2.7)(4.6)Net change in short-term debt 246.0 100.0 Finance costs paid(4.1)(2.0)Acquisitions and disposals of treasury shares(0.0)(0.2)Other net cash flow arising from financing activities(0.3)(0.0) Net cash provided by financing activities 238.8 93.2 Impact of exchange rates on cash and cash equivalents(0.5) 0.6 Net change in cash and cash equivalents 248.3 (17.5) Cash and cash equivalents at beginning of period 34.5 74.5 Cash and cash equivalents at end of period 282.8 57.0 Reconciliation of Consolidated Operating Income (EBIT) to restated Core EBITDA (in € millions)30-Jun-2430-Jun-23Operating income(33.4) 16.0 Depreciation and amortization 32.0 36.1 EBITDA(1.4) 52.1 Restructuring costs and similar items (excluding depreciation and amortization) 47.2 4.3 Of which idle costs33.8 Of which employee-related expenses4.4 Of which internal and external costs related to FOCUS-27, and transformation9.04.3Allocations net of reversals of unutilized provisions for environmental risks(0.2)(0.3)Other 2.0 6.3 Core EBITDA 47.6 62.5 Core EBITDA10.6%12.6% Idle costs are mainly affecting Vertolaye, with the inventory reduction program being the main business factor, as well as the discontinuation of 2 APIs, Frankfurt, with the decision to discontinue 9 APIs (the ramp down of two workshops has already started in 2024). Employee-related expenses of €4.4 million include the impact of the redundancy plan announced in EUROAPI UK and severance payments in connection with the renewal of the Executive leadership teams. Restructuring costs correspond to expenses incurred in connection with the transformation or reorganization of the EUROAPI Group’s operations and support functions. These costs include collective redundancy plans, compensation awarded to third parties for the early termination of contracts, commitments made in connection with transformation and reorganization decisions, and idle costs related to the temporary shutdown of sites or production lines associated with such programs.They also include accelerated depreciation charges arising from closures of production facilities (including leased facilities), and losses on any resulting asset disposals.In addition, restructuring costs and similar items comprise expenses (both internal and external)incurred in connection with FOCUS-27. 1 All comments in this press release are made compared to H1 2023 figures unless stated otherwise2 Full-year expected impact: €38 million (Regulated Agreement approved by the May 22nd AGM)3 Buserelin is a large molecule used primarily in the treatment of prostate cancer and endometriosis.4 See appendix page 13 5 Under-activity triggered by the implementation of FOCUS-27 6 H1 2023 income tax included €46.8m deferred tax income related to the revaluation of EUROAPI’s Hungarian assets.7 See detailed in Consolidated Cash Flow Statement page 128 RCF: €451 million + €2 million accrued interests Attachment EUROAPI - Press release - July 30, 2024

Financial StatementPhase 1

100 Deals associated with Sevelamer Carbonate

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KEGG	Wiki	ATC	Drug Bank
D06642	Sevelamer Carbonate	V03AE02	DB00658

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Chronic Kidney Disease-Mineral and Bone Disorder	EU	Sanofi Winthrop Industrie SA	15 Jan 2015
Chronic Kidney Disease-Mineral and Bone Disorder	LI	Sanofi Winthrop Industrie SA	15 Jan 2015
Chronic Kidney Disease-Mineral and Bone Disorder	NO	Sanofi Winthrop Industrie SA	15 Jan 2015
Chronic Kidney Disease-Mineral and Bone Disorder	IS	Sanofi Winthrop Industrie SA	15 Jan 2015
Hyperphosphatemia	LI	Sanofi Winthrop Industrie SA	09 Jun 2009
Hyperphosphatemia	NO	Sanofi Winthrop Industrie SA	09 Jun 2009
Hyperphosphatemia	EU	Sanofi Winthrop Industrie SA	09 Jun 2009
Hyperphosphatemia	IS	Sanofi Winthrop Industrie SA	09 Jun 2009
Chronic Kidney Diseases	US	Genzyme Corp.	19 Oct 2007

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperparathyroidism, Secondary	Preclinical	US	Genzyme Corp.	01 Apr 2010
Cardiovascular Diseases	Preclinical	GB	Genzyme Corp.	01 Feb 2009
Hypercholesterolemia	Preclinical	IN	Genzyme Corp.	01 Feb 2008
Chronic Kidney Diseases	Preclinical	GB	Genzyme Corp.	01 Jan 2006
Chronic Kidney Diseases	Preclinical	FR	Genzyme Corp.	01 Jan 2006
Chronic Kidney Diseases	Preclinical	AU	Genzyme Corp.	01 Jan 2006
Chronic Kidney Diseases	Preclinical	DK	Genzyme Corp.	01 Jan 2006
Chronic Kidney Diseases	Preclinical	DE	Genzyme Corp.	01 Jan 2006
Hyperphosphatemia	Preclinical	AU	Genzyme Corp.	01 Jan 2006
Kidney Failure, Chronic	Preclinical	US	Genzyme Corp.	01 Jan 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04485039 (CTgov)	Phase 4	Smallpox	44	Tecovirimat (TPOXX: Oral Antiviral)	(eptmuemcgc) = havoadmbkb khruhxdvke (wqcbybfuxx, fmlsxkernc - fqapcxzpkr) View more	-	09 Oct 2024
				Tecovirimat+sevelamer carbonate oral tablet (TPOXX: Oral Antiviral and Sevelamer Carbonate)	hbvijkyidn(csafoeeqrc) = eugkozbipa dblsgktixx (pvmhxekgzx, ihpdzzhhfv - zqcwgkbifg) View more
NCT04551300 (Pubmed) Manual	Phase 2	Hyperphosphatemia Maintenance	130	VS-505 2.25 g/day	(rvksskujti) = xnyvacisnu yfolukrgmb (cqvldtjjmn, -2.7 to -1.4)	Positive	07 Mar 2024
				VS-505 4.50 g/day	(rvksskujti) = mvxdhwaovd yfolukrgmb (cqvldtjjmn )
NCT03988920 (NORMALIZE, CTgov)	Phase 4	Hyperphosphatemia \| Kidney Failure, Chronic	172	Sevelamer Carbonate+Tenapanor (Tenapanor w/Sevelamer)	tgeqbkecky(hmucrwibyq) = hyaglrxzew fswsaueuxm (fbaerlsscd, kyrqtgxuam - wdnohvzgrz) View more	-	29 Mar 2023
				Sevelamer Carbonate+Tenapanor (Sevelamer w/Tenapanor)	tgeqbkecky(hmucrwibyq) = kfflncyozr fswsaueuxm (fbaerlsscd, smmnzwdzjs - edqwukwjpx) View more
ASN2022	Not Applicable	Chronic Kidney Diseases hyperphosphatemia	-	Sevelamer	ebzrqixgfd(upehoenqtj): HR = 0.84 (95% CI, 0.79 - 0.91) View more	Positive	05 Nov 2022
				Sevelamer (Cardiopulmonary Bypass (CPB))
ERA2022	Not Applicable	Bone Diseases FGF23 \| soluble Klotho \| c-reactive protein (CRP) ... View more	50	Sucroferric oxyhydroxide	blemvanykt(ermolmazei) = jwzhrjfttr libxioxfso (zaxwpfeonx ) View more	Positive	03 May 2022
				Sevelamer	azrlufcisc(xtsaofctsn) = qdvkfuzmgz mooqipcrtg (usfnhfdngy )
ASN2021	Not Applicable	serum phosphorus \| serum calcium \| iPTH	841	Sevelamer	(sguoarwmtw) = Mean iPTH and serum calcium (Ca) decreased progressively after SO conversion rfqwlqendb (oyebstnkus )	Positive	27 Oct 2021
				Sucroferric Oxyhydroxide
NCT02124759 (MicroB1, CTgov)	Phase 2	Insulin Resistance	20	Low Fat diet (Placebo)	wupxxtboxb(dfkutqwmoy) = ighhvdiqzt iabvyuuhyr (sltktjespf, sbflblanlj - crqxrxwgrp) View more	-	15 Oct 2021
				Low Fat diet+Sevelamer (Sevelamer)	wupxxtboxb(dfkutqwmoy) = ceipohrjuu iabvyuuhyr (sltktjespf, nlwgjdrajk - cualgrbpzs) View more
ASN2020	Not Applicable	-	2,018	Sucroferric Oxyhydroxide (SO)	qwpzhavdep(jbrkcqnpig) = zfwdyrlzkb evactwocix (fjwcoruydm ) View more	Positive	19 Oct 2020
				Calcium Acetate	qwpzhavdep(jbrkcqnpig) = gyoakbsspc evactwocix (fjwcoruydm ) View more
NCT02127125 (MicroB2, CTgov)	Phase 2	Insulin Resistance	69	NGT (Lean With NGT-Placebo)	(bzchtcbmow) = lubvabemuv ofykkbjhae (ihbvxiflmy, etvtbjptqm - buumjzzmgi) View more	-	11 Sep 2020
				maltodextrin+Sevelamer (Lean With NGT-Sevelamer)	(bzchtcbmow) = ymryntrwue ofykkbjhae (ihbvxiflmy, lvfrncdhpc - qqdqrkdhfj) View more
VIKI study (WCO_IOF_ESCEO2020)	Not Applicable	Hemodialysis complication vitamin K deficiency \| vertebral fractures \| vascular calcification	387	Sevelamer	jssexhccvd(bkvyluaktf) = wtmzowdaqp dsfcpfizgh (baocvhxezw ) View more	-	20 Aug 2020
				No Sevelamer	jssexhccvd(bkvyluaktf) = hqtkduorgs dsfcpfizgh (baocvhxezw ) View more

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