This study aimed to compare the gonadotropin-releasing hormone agonist (ultra-short) protocol versus (short and long) protocols on ovarian reserve in women undergoing intracytoplasmic sperm injection

Start Date15 Oct 2022

Sponsor / Collaborator

Tanta University

NCT05050084

/ RecruitingPhase 3IIT

Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)

This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Decipher score in this study is used for patient selection and the two variations of treatment to be studied: intensification for higher Decipher score or de-intensification for low Decipher score. Patients with higher Decipher risk score will be assigned to the part of the study that compares the use of 6 months of the usual treatment (hormone therapy and radiation treatment) to the use of darolutamide plus the usual treatment (intensification). The purpose of this section of the study is to determine whether the additional drug can reduce the chance of cancer coming back and spreading in patients with higher Decipher score. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. Alternatively, patients with low Decipher risk score will be assigned to the part of the study that compares the use of radiation treatment alone (de-intensification) to the usual approach (6 months of hormone therapy plus radiation). The purpose of this part of the study is to determine if radiation treatment alone is as effective compared to the usual treatment without affecting the chance of tumor coming back in patients with low Decipher score prostate cancer. Radiation therapy uses high energy to kill tumor cells and reduce the tumor size. Hormone therapy drugs such as darolutamide suppress or block the production or action of male hormones that play role in prostate cancer development. Effect of radiation treatment alone in patients with low Decipher score prostate cancer could be the same as the usual approach in stabilizing prostate cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy.

Start Date06 Dec 2021

Sponsor / Collaborator

NRG Oncology

[+1]

NCT04513717

/ RecruitingPhase 3IIT

Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)

This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.

Start Date21 Jan 2021

Sponsor / Collaborator

NRG Oncology

[+1]

100 Clinical Results associated with Buserelin Acetate

100 Translational Medicine associated with Buserelin Acetate

100 Patents (Medical) associated with Buserelin Acetate

2,496

Literatures (Medical) associated with Buserelin Acetate

17 Feb 2025·Immunological Investigations

Buserelin Promotes the Differentiation and Function of Macrophage-Colony-Stimulating Factor-Producing T Helper Cells

Article

Author: Jian, Lei ; Li, Hua ; Zheng, Aini ; Xiang, Jin-Bo

BACKGROUNDBuserelin has been used to treat central precocious puberty (CPP). However, it could potentially result in immune dysregulation to undermine patients' health. Therefore, it is necessary to elucidate the effects of buserelin on immune cells. Here we explored buserelin-induced impacts on the differentiation and function of macrophage-colony-stimulating factor-producing T helper (ThGM) cells to uncover the immunoregulatory role of buserelin.METHODSRat CPP was induced by danazol injection followed by buserelin treatment. The frequencies of ThGM cells in the spleen and lymph nodes were evaluated by flow cytometry. ThGM cell generation and function were analyzed in cell culture assays. Cell signaling was measured by Immunoblotting.RESULTSBuserelin increased the frequencies of splenic and lymph node ThGM cells. Buserelin promoted the in vitro differentiation and proliferation of ThGM cells. Buserelin-treated ThGM cells showed stronger supportive effects on other effector T helper cells. Buserelin induced the activation of the nuclear factor of activated T cells and extracellular signal-regulated kinase 1/2 in ThGM cells.CONCLUSIONBuserelin enhances the differentiation and function of pro-inflammatory ThGM cells, thus increasing the risk of autoimmune or inflammatory disorders. Therefore, it is necessary to monitor ThGM cells in buserelin-treated children to prevent latent immune dysregulation.

18 Nov 2024·ACS Applied Bio Materials

Mechanistic Model for Drug Release from PLGA-Based Biodegradable Implants for In Vitro Release Testing: Development and Validation

Article

Author: Telaprolu, Krishna Chaitanya ; Bois, Frederic Y. ; Puttrevu, Santosh Kumar ; Arjmandi-Tash, Omid ; Mittapelly, Naresh ; Polak, Sebastian ; McNally, Kevin ; Djehizian, Alexandre

Several factors can affect drug release from polylactide coglycolide (PLGA)-based formulations, including polymer and drug properties, formulation components, manufacturing processes, and environmental in vitro or in vivo conditions. To achieve optimal release profiles for specific drug delivery applications, it is crucial to understand the mechanistic processes that determine drug release from PLGA-based formulations. In the current study, we developed a mechanistic model for the in vitro drug release of PLGA-based solid implants. The model accounts for all known critical quality attributes (CQAs) and considers the most important release rate processes, including water or dissolution medium influx into the porous structure of the implant, initial noncatalytic hydrolysis of PLGA, autocatalytic hydrolysis, dissolution of oligomers and monomers into the aqueous medium, the liberation of the trapped solid drug from the polymer matrix, dissolution of the solid drug into the wetted pore network, diffusion of the dissolved drug out of the implant, and distribution of the dissolved drug into the dissolution medium. The model has been validated using in vitro release data obtained from implants of four drugs (buserelin, afamelanotide, brimonidine, and nafarelin). The model presented in this manuscript provides valuable insights into the kinetics and mechanism of drug release from PLGA-based solid implants and has demonstrated the potential for optimizing formulation design. The in vitro release model, coupled with physiologically based pharmacokinetic (PBPK) modeling, can predict the in vivo performance of implants and can be used to support bioequivalence studies in a drug development program.

01 Nov 2024·Reproduction in Domestic Animals

Use of Injectable Progesterone as a Pre‐Synchronisation Strategy in a Timed Artificial Insemination Protocol Based on Gonadotropin‐Releasing Hormone and Progesterone in Bos indicus Beef Cows in Anoestrous

Article

Author: Morotti, Fábio ; Seneda, Marcelo Marcondes ; de Camargo, Higor Souza ; Silva, Matheus Cruz ; dos Anjos, Mariana Moreira ; Lollato, João Paulo Mendes ; Barreiros, Thales Ricardo Rigo ; Lorenzetti, Elis

ABSTRACTThis study evaluated the effects of pre‐synchronisation with injectable progesterone (P4) on the ovarian follicular dynamics of Bos taurus indicus cows in anoestrous treated with a timed artificial insemination (TAI) protocol. Multiparous Nelore females (n = 47) at 30–60 days postpartum were used in this study. 10 days before (D‐10) the TAI protocol, antral follicle count (AFC; follicles ≥ 3 mm), ovarian condition and body condition score (BCS; 1–5) were assessed and were randomly allocated into two groups: Pre‐sync (n = 25), which underwent pre‐synchronisation with 150 mg of injectable P4 intramuscularly (i.m.), and control (n = 22), which received the same volume of NaCL 0.9%. On D0, the ovarian assessment was repeated, and TAI protocol was initiated in all animals, with the insertion of an intravaginal P4 device and administration of 10.5 μg of buserelin acetate (gonadotropin‐releasing hormone—GnRH). On D7, the P4 device was removed, and 300 IU of equine chorionic gonadotropin, 150 μg of D‐cloprostenol and 1 mg of estradiol cypionate were administered i.m. On the same day (D7), the presence of the corpus luteum (CL) was assessed, the dominant follicle was measured, and the tail was painted to evaluate estrous expression. On D9, the largest follicle was remeasured, and TAI was performed. Animals that were not detected in oestrous at the time of AI were administered 10.5 μg of GnRH i.m. Numerical data were analysed using the Mann–Whitney U test. Binary data were analysed using the Fisher's exact test (5%). BCS, both at the beginning of pre‐synchronisation (p = 0.45) and TAI protocol initiation (p = 0.20), and AFC (p = 0.36) did not differ between control and Pre‐sync groups. The diameter of the largest follicle was similar between the control and Pre‐sync groups on D‐10 (p = 0.32), D0 (p = 0.33), D7 (p = 0.29) and D9 (p = 0.22). On D7 of the protocol, the Pre‐sync group had a higher percentage of CL visible on transrectal ultrasonography (84.0%; p = 0.02) than the control group (54.5%); however, the expression during oestrous did not differ between groups (p = 0.59). The pregnancy rate was similar (p = 0.64) between groups and was not influenced by the CL rate on D7 (p = 0.48), oestrous expression (p = 0.20) or their interaction (p > 0.1). Pre‐synchronisation effectively increased the proportion of cows with CL on D7 without altering the diameter of the largest follicle, oestrous expression or pregnancy rate in anoestrous cows treated with a GnRH/P4‐based TAI protocol.

News (Medical) associated with Buserelin Acetate

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

10 Jul 2024

·synapse.patsnap.com

GPCR Family Anticancer Targets and Marketed Therapeutic Drugs (Part 1)

This article will inventory the anti-tumor targets in the GPCR family and the therapeutic drugs that have been marketed. 01 GnRHRGonadotropin-Releasing Hormone Receptor is a member of the seven-transmembrane GPCR (G protein-coupled receptor) family. It is expressed on the surface of pituitary gonadotropin cells, as well as lymphocytes, mammary glands, ovaries, and prostates. Upon binding with gonadotropin-releasing hormone, the receptor associates with G proteins that activate the phosphatidylinositol-calcium second messenger system. Activation of the receptor ultimately leads to the release of gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Leuprolide (Leuprorelin) is a synthetic analogue of gonadotropin-releasing hormone (GnRH) developed by Takeda Pharmaceuticals, commonly used for treating certain types of hormone-dependent cancers, such as prostate and breast cancers, as well as non-cancerous conditions like endometriosis, uterine fibroids, and certain types of infertility. Leuprolide mimics the natural GnRH signals in the brain, initially causing a transient increase in hormone levels, followed by suppression of hormone production, thereby reducing symptoms and growth of these hormone-dependent diseases. Leuprolide is an injectable, administered via subcutaneous or intramuscular injection. Due to its control over hormone levels, Leuprolide is also used in treating precocious puberty in children. Additionally, GnRH analogues such as Goserelin developed by AstraZeneca, Buserelin by Sanofi, Nafarelin by Pfizer, and Gonadorelin by Mitsubishi Tanabe are all agnostic drugs of the GnRHR type. In recent years, antagonist drugs targeting GnRHR have also been reported for the treatment of certain hormone-dependent diseases. For instance: Degarelix is a GnRH receptor antagonist developed by Ferring Pharmaceuticals for the treatment of prostate cancer. It is also the first antagonist drug targeting the GnRHR globally, inhibiting the production of sex hormones (such as testosterone) by blocking the GnRH receptor, thereby suppressing the growth of prostate cancer cells. It is typically administered as an injection, rapidly reducing testosterone levels to castration levels. Ferring Pharmaceuticals subsequently licensed the commercial rights for Degarelix to Astellas and Pfizer. Relugolix is another GnRH receptor antagonist used for treating advanced prostate cancer. It also works by blocking the GnRH receptor and lowering sex hormone levels. Relugolix is also under investigation for the treatment of uterine fibroids and endometriosis. Relugolix was originally developed by Takeda Pharmaceuticals and is the first small molecule drug globally targeting the GnRH receptor. Linzagolix is an oral GnRH receptor antagonist for the treatment of various hormone-dependent diseases including endometriosis and uterine fibroids. Linzagolix has been approved in the European Union and the UK for treating moderate to severe symptoms associated with uterine fibroids. 02 SSTRThe Somatostatin Receptor Type (SSTR) belongs to the GPCR (G-protein-coupled receptor) family and comprises five subtypes (SSTR1-SSTR5). SSTRs play a critical role in the endocrine and nervous systems and are potential targets for the treatment of multiple diseases, particularly neuroendocrine tumors (NETs). Somatostatin (SST) is the natural ligand for SSTRs, and cortistatin (CST) is a neuropeptide that also binds with high affinity to all subtypes of SSTRs. Due to the high sequence homology between different SSTR subtypes, developing drugs that can selectively modulate specific subtypes presents a challenge, but this is essential for minimizing off-target effects. In targeted SSTR therapies, peptide radioligand therapies represent a significant research focus. For instance, Novartis's (177Lu)Lutathera, a peptide radioligand therapy targeting SSTR2, has been approved for the treatment of adult patients with SSTR-positive gastroenteropancreatic neuroendocrine tumors. The illustration below shows the differential tissue distribution of various SSTRs. Exploring dual-target drugs is an innovative direction, where the advantage of bi-targeted radiopharmaceuticals lies in the potential synergistic effects between the two targets, thereby enhancing safety and efficacy. Radiopharmaceutical development is exploring new indications such as pancreatic cancer, renal cancer, stomach cancer, thyroid cancer, lung cancer, and Parkinson's disease to broaden the therapeutic spectrum. Somatostatin is a polypeptide hormone composed of 14 amino acid residues, including a single disulfide bond. This hormone inhibits the secretion of growth hormone, insulin, glucagon, gastrin, pancreatic enzymes, and thyrotropin. However, due to its very short half-life in the body (less than 3 minutes), its therapeutic value is limited. Research on the β-turn pharmacophore of somatostatin has led to the development of more biologically stable and potent analogs. Octreotide was developed based on this lead sequence and approved for treating acromegaly, adenomas, and pancreatic, breast, and prostate tumors. DOI: 10.3390/molecules25174012 Subsequent research has pushed the development of selective receptor antagonists such as lanreotide, vapreotide, and pasireotide, and has introduced peptide imaging and peptide receptor radionuclide therapy. In these radiological therapies, radioactive elements like 111In, 90Y, 68Ga, or 99mTc are linked to selective somatostatin analogs through chelating groups, which led to the approval of radiopharmaceutical preparations such as 111In-labeled pentetreotide, 99mTc-labeled depreotide, 68Ga-labeled DOTA-TATE and DOTA-TOC, and 64Cu-labeled DOTA-TATE. These drugs are used for tumor detection. Several synthetic peptides and radiopharmaceuticals targeting SSTRs have been approved for market, with representative drugs including: Octreotide, developed by Novartis as a synthetic octapeptide somatostatin analog, is an SSTR agonist. Clinically, it is primarily used to treat conditions such as acromegaly, thyrotoxicosis, gastrointestinal fistulas, and symptoms and signs associated with gastroenteropancreatic neuroendocrine tumors. Octreotide inhibits the secretion of growth hormone, thyroid-stimulating hormone, insulin, and glucagon by binding to SSTRs, especially subtypes SSTR2 and SSTR5. Pentetreotide is another synthetic octapeptide that, unlike Octreotide, forms the radioactive drug 111In-pentetreotide by binding to the radiolabeled isotope Indium-111 via the chelator DTPA. This compound enables the use of Pentetreotide in single photon emission computed tomography (SPECT) imaging to detect tumors expressing SSTRs. It has a relatively fast renal clearance rate, offering a significant advantage over the first-generation [123I-Tyr3]-octreotide, a radioactive iodine-labeled octapeptide somatostatin analog. However, it has shortcomings, such as the need for a high tumor/noise intensity ratio, lower imaging resolution, medium affinity for receptors, and high γ-energy, which results in a higher radiation dose to patients. 111In-pentetreotide Lanreotide is a synthetic somatostatin analog, belonging to octapeptide derivatives. It has structural and functional similarities to Octreotide, but with different pharmacokinetic properties that make it a long-acting somatostatin analog. Gallium Dotatate Ga-68, developed by Advanced Accelerator Applications, is a radioactive diagnostic agent that uses DOTA to chelate Gallium-68 for positron emission tomography (PET) imaging, mainly targeting neuroendocrine tumors (NETs) expressing somatostatin receptors. The three radioactive drugs differ slightly in pharmacokinetic properties, primarily due to variations in affinity for specific receptor subtypes. [68Ga]-DOTATATE specifically binds to SSTR2, indicating its primary interaction with this receptor subtype; [68Ga]-DOTATOC has high affinity for SSTR2 and moderate affinity for SSTR5; while [68Ga]-DOTANOC shows high affinity for SSTR2, SSTR3, and SSTR5, making it a broad-target drug for multiple receptor subtypes. Lutetium Lu-177 dotatate, another therapeutic radiopharmaceutical developed by Advanced Accelerator Applications, targets tumor cells by binding to SSTR, particularly SSTR2 subtype. This binding allows the radioactive isotope Lutetium-177 to emit β-particles, thereby killing tumor cells. Yttrium-90 (a pure high-energy β-emitter with a half-life T1/2 = 64 hours) and Lutetium-177 (a moderate energy β-emitter with a half-life T1/2 = 6.7 days) are the most commonly used elements in peptide receptor radionuclide therapy. Each has specific advantages for targeted therapy. 90Y has higher particle energy and penetration, useful for treating larger tumors, while 177Lu, emitting lower-energy radiation, is better suited for smaller tumors. Additionally, its γ-radiation energy allows for scintigraphy scanning and dose determination during therapy. The image above shows [68Ga]-DOTATOC (commercial name Somakit®) and [177Lu]-DOTATATE (commercial name Lutatherav®), which are used to treat patients with progressive metastatic midgut neuroendocrine tumors. In October 2017, Novartis acquired French innovator Advanced Accelerator Applications for $3.9 billion to build and expand its radioligand therapy platform. In 2018, Novartis further invested $2.1 billion to acquire the biopharmaceutical company Endocyte, gaining more radiopharmaceutical candidates. Through these acquisitions, Novartis has established and expanded its radioligand therapy platform, holding several marketed products like Lutathera (177Lu-DOTATATE) and 68Ga-Edotreotide, along with many in development, including 177Lu-PSMA-617, 177Lu-PSMA-R2, 177Lu-NeoB, 177Lu-FF58, and 255Ac-PSMA-617. According to the Synapse database, multiple drugs targeting SSTRs or selectively targeting different SSTR subtypes are approved for the market or are in clinical research, with radiopharmaceuticals and diagnostics focusing on this target being particularly noteworthy. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

100 Deals associated with Buserelin Acetate

External Link

KEGG	Wiki	ATC	Drug Bank
D01831	Buserelin Acetate	L02AE01	DB06719

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Endometriosis	Japan	Sanofi KK	01 Aug 1988
Endometriosis	Japan	Clinigen KK	01 Aug 1988
Infertility	Japan	Sanofi KK	01 Aug 1988
Infertility	Japan	Clinigen KK	01 Aug 1988
Leiomyoma	Japan	Sanofi KK	01 Aug 1988
Leiomyoma	Japan	Clinigen KK	01 Aug 1988
Puberty, Precocious	Japan	Clinigen KK	01 Aug 1988
Puberty, Precocious	Japan	Sanofi KK	01 Aug 1988

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02703584 (Pubmed \| Hum Reprod)	Phase 4	-	276	GnRH agonist and hCG (dual trigger)	vjbtendmoq(rsgpxpuwep) = wzvpqqvorg otyqouvesn (tojuhkmaag ) View more	-	01 Jul 2020
				hCG trigger	vjbtendmoq(rsgpxpuwep) = pszpyfwwvr otyqouvesn (tojuhkmaag ) View more
ASCO_GU2019	Not Applicable	Prostatic Cancer	1,233	s-ADT with buserelin	axrpywdylh(ceuugtyjaa) = dydsuhszvo tuxistdkas (esvzthefrj ) View more	Positive	26 Feb 2019
ASCO_GU2016	Not Applicable	Prostatic Cancer Neoadjuvant \| Adjuvant	670	Buserelin	mpncshhfgv(fhwxcndhff) = nessbgpivu hymxqorzss (ejxqfvpmpe )	-	10 Jan 2016
				Goserelin	mpncshhfgv(fhwxcndhff) = fbezygiqcu hymxqorzss (ejxqfvpmpe )
NCT00004054 (RTOG-9902, CTgov)	Phase 3	Localized Prostate Carcinoma	397	Radiation therapy+triptorelin+buserelin+bicalutamide+flutamide+goserelin+leuprolide (Hormones and RT)	(qbfzqmjkya) = bmghmtnmep ukupwakpmv (wxgbrmxxvo, eoizkhsobx - vtfaxmtazn) View more	-	07 Jan 2015
				Radiation therapy+warfarin+etoposide+estramustine phosphate sodium+paclitaxel+bicalutamide+flutamide (Hormones and RT Plus Chemotherapy)	(qbfzqmjkya) = dwwzufnvbv ukupwakpmv (wxgbrmxxvo, ucayuvtsqj - huaqcdzxqg) View more
UEGW2014	Not Applicable	Visceral Neuropathy, Familial, Autosomal Dominant	-	Buserelin	arnzbsxced(kqsnlpbakm) = The treated rats have exhibited a more stressed behavior than controls viefejwnlc (xhvbkbmmot ) View more	-	01 Oct 2014
				Saline
UEGW2014	Not Applicable	Visceral Neuropathy, Familial, Autosomal Dominant	-	Buserelin	(xagbuwvgyf) = ilorseyoty xndmsptopt (eqzcsesyju ) View more	-	01 Oct 2014
				Saline	owjcmyifau(nbfqdswnos) = mbmmbkbjsa qqcknwaect (eysurdqqki, 2.9 - 3.9) View more
NCT00461916 (Pubmed \| Hum Reprod)	Phase 4	Ovarian Stimulations	182	Half-dose depot triptorelin	ghrhzelhjs(cxxwahdrno) = egxzacaple ubqdrkeljx (rswiobmarq, (1.8))	-	01 Sep 2007
				Reduced-dose daily buserelin	ghrhzelhjs(cxxwahdrno) = fngczatevu ubqdrkeljx (rswiobmarq, (1.9))

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis