A Phase IIIb Study to Characterize the Effectiveness and Safety of Adjuvant Ribociclib in a Wide Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)

An open-label, multicenter, phase IIIb, single-arm study to evaluate the safety and efficacy of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a wide patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, II (subset) or I (high-risk subset as exploratory cohort) early Breast Cancer (EBC)

Start Date30 Apr 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06654336 / Not yet recruitingPhase 2IIT

Phase II Randomized Trial of Recurrence-directed Therapy (RDT) with or Without Androgen-Deprivation Therapy (ADT) in Radio-recurrent Oligo-metastatic Hormone/Castrate Sensitive Prostate Cancer (romCSPC).

The goal of this study is to determine whether the addition of Androgen Deprivation Therapy (ADT) utilizing the study drug ELIGARD® to Recurrence- Directed Therapy (RDT) improves progression-free survival (PFS) compared to RDT alone in patients with early radio-recurrent oligo-metastatic castrate / hormone sensitive prostate cancer (romCSPC). Participants will be assessed at standard of care clinic visits every 3 months. The follow-up period is 36 months.

Start Date15 Apr 2025

Sponsor / Collaborator

Ontario Clinical Oncology Group

[+2]

NCT06650579 / Not yet recruitingPhase 3IIT

Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: the REVELUTION-2 Trial

This phase III/IV trial compares the impact of leuprolide and abiraterone acetate (AA) versus relugolix and AA on the heart in hormone-naive patients with advanced prostate cancer receiving pelvic radiation therapy. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa). It prevents the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate tumor cells that need testosterone to grow. Abiraterone acetate, an androgen biosynthesis inhibitor, works by decreasing the amount of certain hormones in the body. Relugolix, a GNRH antagonist, works by decreasing the amount of testosterone produced by the body. This may slow or stop the spread of prostate tumor cells that need testosterone to grow. The use of hormone therapy with radiation therapy has been shown to improve survival, however, studies have suggested that the addition of hormone therapy may worsen heart (cardiac) disease and high blood pressure. In fact, studies have shown that the most common cause of death in prostate cancer patients is due to heart disease or heart attacks. Computed tomography (CT) scans create a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. In this study, sophisticated cardiac CT images are used to take pictures of patients' heart and coronary arteries to help assess damage to the heart. Using cardiac CT and blood tests, this trial may help doctors determine which patients are at risk of cardiac disease when treated with combination hormone therapy, as well as the differential risk of leuprolide versus relugolix in combination with abiraterone acetate.

Start Date16 Dec 2024

Sponsor / Collaborator

Emory University

[+4]

100 Clinical Results associated with Leuprolide Acetate

100 Translational Medicine associated with Leuprolide Acetate

100 Patents (Medical) associated with Leuprolide Acetate

1,639

Literatures (Medical) associated with Leuprolide Acetate

01 Jan 2025·Drug delivery and translational research

Effect of PLGA raw materials on in vitro and in vivo performance of drug-loaded microspheres

Article

Author: Walker, Jennifer ; Schwendeman, Steven P ; Olsen, Karl F ; Beck-Broichsitter, Moritz ; Liang, Desheng ; Schwendeman, Peter S ; Chandrashekar, Aishwarya ; Ackermann, Rose

Poly(lactide-co-glycolide) and poly(lactic-co-glycolic acids) (PLGAs) play a critical role in the development of commercial long-acting injectable microsphere formulations. However, very little information is available describing the impact of PLGA manufacturer and monomer distribution along the polymer chain (e.g., glycolic blockiness (R_c) and average lactic block length (L_L)) on the degradation and release behavior of PLGA drug carriers in vitro and in vivo. Here, we compared the in vitro and in vivo performance of (a) four leuprolide-loaded microsphere formulations prepared from similar low-molecular-weight acid-capped PLGAs (10-14 kD, i.e., Expansorb^® DLG 75-2A, Purasorb^® PDLG 7502A, Resomer^® RG 752H and Wako^® 7515) and (b) two triamcinolone acetonide-loaded (Tr-A) microsphere formulations from similar medium-molecular-weight ester-capped PLGAs (i.e., Expansorb^® DLG 75-4E and Resomer^® RG 753S). Lupron Depot^® and Zilretta^® were used as reference commercial products. The six 75/25 PLGAs displayed block lengths that were either above or below values expected from a random copolymer. Drug release and polymer degradation were monitored simultaneously in vitro and in vivo using a cage implant system. The four leuprolide-loaded formulations showed similar release and degradation patterns with some notable differences between each other. Microspheres from the Expansorb^® polymer displayed lower L_L and higher R_c relative to the other 3 PLGA 75/25 microspheres, and likewise exhibited distinct peptide release and degradation behavior compared to the other 3 formulations. For each formulation, leuprolide release was erosion-controlled up to about 30% release after the initial burst followed by a faster than erosion release phase. In vitro release was similar as that in vivo over the first phase but notably different from the latter release phase, particularly for the most blocky Expansorb^® formulation. The Purasorb^® and Wako^® formulations displayed highly similar performance in release, degradation, and erosion analysis. By contrast, the two ester-capped Expansorb^® DLG 75-4E and Resomer^® RG 753S used to prepare Tr-A microspheres shared essentially identical L_L and higher R_c and behaved similarly although the Expansorb^® degraded and released the steroid faster in vivo, suggestive of other factors responsible (e.g., residual monomer). The in vivo release performance for both drugs from the six microsphere formulations was similar to that of the commercial reference products. In summary, this work details information on comparing the similarities and differences in in vitro and in vivo performance of drug-loaded microspheres as a function of manufacturing and microstructural variables of different types of PLGA raw materials utilized and could, therefore, be meaningful in guiding the source control during development and manufacturing of PLGA microsphere-based drug products. Future work will expand the analysis to include a broader range of L_L and higher R_c, and add additional important formulation metrics (e.g., thermal analysis, and residual monomer, moisture, and organic solvent levels).

17 Dec 2024·JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

A rare case of central precocious puberty in a male infant with adrenal hypoplasia congenita

Article

Author: Lane, Andrew H. ; Mastoropoulou, Aikaterini

Abstract:

Objectives:

We describe a male with adrenal hypoplasia congenita (AHC) caused by a novel mutation in NR0B1, who was noted at 9 months of age to have central precocious puberty (CPP).

Case presentation:

A 3-week-old full-term male presented with hypothermia and lethargy, and a 0.3 kg weight loss since birth. Labs were consistent with adrenal crisis, he was stabilized with stress dose hydrocortisone (HC), insulin, and antibiotics, and he was admitted to the Pediatric Intensive Care Unit. Subsequent labs revealed primary adrenal insufficiency with abdominal ultrasound remarkable for nonvisualization of the adrenal glands. Genetic testing identified a novel pathogenic c.707G>A [p.Trp236ter] nonsense variant in the DNA-binding domain of NR0B1 (DAX-1) confirming AHC. The patient was discharged with HC, fludrocortisone, and sodium supplementation with good tolerance and interval weight gain and normal electrolytes. At 9 months of age, the patient developed signs of precocious puberty, which failed to self-resolve or diminish with increased dosing of HC, and by the age of 15 months, he was treated with leuprolide acetate.

Conclusions:

Historically, hypogonadotropic hypogonadism has been observed in 76 % of adolescent patients with AHC who have alterations in NR0B1. CPP has been infrequently described in AHC, and the natural history and management of CPP in this setting is not established. Our observations may contribute to the understanding of factors influencing normal and abnormal puberty in infants. Increased awareness of the possibility of CPP in AHC will aid clinicians in the earlier clinical and laboratory detection of this complication.

01 Nov 2024·JOURNAL OF CONTROLLED RELEASE

Implant dynamics, inner structure, and their impact on drug release of in situ forming implants uncovered through CT imaging

Article

Author: Masese, Francis K ; Lin, Xinhao ; Hargrove, Derek ; Yuan, Hong ; Zhen, Zixuan ; Darji, Mittal ; Al Zouabi, Nour N ; Qin, Bin ; Li, Qi ; Zhang, Qiangnan ; Lu, Xiuling ; Jay, Michael ; Ward, Lauren Elizabeth ; Kasi, Rajeswari M ; O'Reilly Beringhs, André ; Wang, Yan

In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. The process of implant formation, inner structure change and their impact on drug release were elucidated. Real-time drug distribution was unveiled by the CT contrast agent, iohexol, where it shows a core-shell structure of the deposition. The incorporation of leuprolide acetate (LA) led to a reduced extent of burst release, prolongated release profile, and extended implant size expansion. LA was found to interact with the solvent and slowed down the polymer phase inversion, thus significantly changed the drug distribution in the implant and reduced the drug release. The implant inner structure identified through SEM, implant size change, and polymer degradation along with the CT real time imaging all consistently support the implant formation differences and their implant on the drug release. Similar patterns of implant size expansion and iohexol distribution in the implants were observed both in vitro and in vivo for the implants with and without LA. The comprehensive understanding of the impact of implant formation on drug release through real time CT imaging facilitates the ISFI product development and evaluation.

News (Medical) associated with Leuprolide Acetate

09 Dec 2024

·www.biopharmadive.com

Endometriosis drug research, long underfunded, confronts familiar problems in women’s health

Ally Schott felt lonely when she was diagnosed with endometriosis at the age of 12. With few treatment options and limited information to go on, she and her family had to become self-taught medical researchers.Even the diagnosis was the result of Schotts mother connecting the dots between the pain her daughter was experiencing and the symptoms described by women in a patient organization she had found.That's ultimately what convinced my parents that this is what I was dealing with seeing and reading about the experience of others, and recognizing that I was going through something similar, Schott said.In some ways, Schotts case is rare. Her diagnosis came early, unlike some women who dont learn they have endometriosis for a decade or more due to lack of disease awareness, misdiagnosis or even bias that assumes severe menstrual pain is normal.It's very, very easy to dismiss someone's discomfort if you believe something is meant to be uncomfortable, said Somer Baburek, CEO and co-founder of Hera Biotech, a biotechnology company developing a nonsurgical tool to diagnose endometriosis.Caused by the growth of uterine tissue outside of the uterus, endometriosis typically affects people who menstruate, but it can occur in post-menopausal women, too. The disease is characterized by chronic pelvic pain, especially during menstruation, but can also cause problems across other parts of the body. It is usually identified through a surgical procedure called a laparoscopy, as ultrasounds cant always image the abnormal tissue growth.Although physicians understanding of the disease has improved, endometriosis root causes remain debated even as it affects some 10% of women and girls globally.[Endometriosis research] has been very underfunded and so, despite the prevalence of this disease, it's not very well understood at all, said Marina R. Walther-Antonio, an assistant professor of surgery at the Mayo Clinic in Minnesota and a microbiome researcher.When Schott received her diagnosis, there was little she could do about it a reality that frustrated her and her family. I just felt like I finally had the answer, and that if we had the answer to what was wrong, there would be a solution, she said. Even since, only two new drugs for endometriosis-related pain have been approved in the U.S.That pattern is typical of diseases, like endometriosis, that primarily or only affect women. Insufficient funding of womens health research has stifled development of new products, resulting in prevalent conditions with hardly any available treatments. And while clinical trials are more inclusive than they were in the 1990s and earlier, studies are not always set up to tease out why or how disease symptoms may differ on the basis of biological sex.Information deficitsDevelopment of a drug is no easy feat for any condition. But the process is more difficult when the disorder isnt well understood, as with endometriosis.We're starting from multiple deficits, and one of them is an information deficit, said Heras Baburek. And I think that's something that all founders in women's health struggle from.For instance, researchers sometimes use biobanks collections of medical and biological data from tissue, blood and DNA samples to identify molecular markers of a disease, or develop effective diagnostics. If collected by a government-funded program, the data is often published or made available to scientists, providing a starting point for drug research.But such resources are more limited in endometriosis, according to Baburek and Joseph Nassif, an associate professor of obstetrics and gynecology at Baylor College of Medicine and a clinician. While such work has advanced further in other countries, the U.S. is just getting started.So now in the states, we're trying to do a database about all patients who have [endometriosis], Nassif said. We have banks for cancer and banks for other diseases. Once you have a lot of patients, we can study it better.With less of a foundation, drug developers taking aim at endometriosis, or other womens health conditions like polycystic ovary syndrome or premenstrual dysphoric disorder, can have a harder time starting out.When you're building the data story of your company, yours looks weaker than companies who are focused on indications outside of women's health, because they have access to all of those resources, Baburek said.Such information deficits have deep roots. Up until 30 years ago, the Food and Drug Administration recommended excluding women of childbearing age from participating in Phase 1 and 2 clinical trials, even if they were using contraception. The policies were made in response to birth defects caused by the drug thalidomide, which was prescribed to women to treat nausea in the 1950s and 1960s.A 1993 law mandated the inclusion of women and minorities in clinical research funded by the National Institutes of Health, but the effects of discouraging women from participating in trials have carried through to today.For example, a 2022 study found women made up 41% of participants in Phase 1 through Phase 3 trials for drugs and medical devices run between 2016 and 2019 in the U.S. Women were underrepresented compared to their estimated proportion of the overall patient population for a number of conditions, such as heart disease and psychiatric disorders.Those research gaps, and the knowledge deficits they can cause, ultimately put the lives of girls, women and their families at a huge disadvantage, Schott said.Federal efforts have tried to compensate. Most recently in February, the Biden administration committed to investing $100 million into womens health research. The FDA also recently updated draft guidance to ensure sponsors run more diverse clinical trials, supporting the Food and Drug Omnibus Reform Act of 2022, which requires specific documents and strategic plans.It's really important when you're going to try to understand the efficacy, tolerability and safety of a drug that you're testing it in the representative population of people who you anticipate actually using the product, said Katherine Seay, head of sales and operations at Clinical Trial Media, a patient recruitment and retention company.Limited optionsCompared to other areas of drug R&D, womens health remains underfunded. An analysis of NIH-backed research found that diseases largely affecting men received more funding. The conditions primarily affecting women that do get investment are typically within oncology, such as breast and ovarian cancer, and reproductive medicine.Baburek didnt intend to make reproduction Heras focus, for instance. But the company only gained interest from investors when she mentioned the negative impact endometriosis can have on fertility. While our reproductive organs may be involved in some of these chronic conditions, our ability to reproduce shouldn't be the focus, Baburek said.Hera's struggle for attention isn't an anomaly. Despite its prevalence, endometriosis remains low on drugmaker radar screens.Women with the disease typically take birth control, other hormonal therapies and pain medication to manage symptoms and their menstrual cycles. They may also turn to surgery to either remove the lesions endometriosis causes or, in severe cases, remove their uterus entirely.When Schott was young, the drug Lupron Depot, a hormonal therapy initially approved for the treatment of prostate cancer, was cleared in the U.S. to manage pain associated with endometriosis. The drug can cause side effects similar to that of menopause and was a horrific experience for Schott, who was about 13 years old when it was prescribed to her.Within the past decade, two other products have been approved by the FDA for pain management with endometriosis: AbbVies Orilissa in 2018, and Pfizer and partner Myovant Sciences Myfembree in 2022.The drugs come with hefty price tags: Orilissa and Myfembree each cost over $1,000 per month at their respective list prices. They also dont address the diseases roots, and use is limited to a maximum of two years due to their potential to decrease bone density.Those options are not widely discussed or celebrated because they're not actually treating the disease, Baburek said. [They are] just quieting some of the symptoms that make your life unbearable, but then you get a whole host of other symptoms that also might make your life unbearable.Schott was prescribed Myfembree as an adult, but never took it because of its limitations and potential effects on bone density. She says she likely wouldn't take Orilissa for the same reasons.For the moment being, we have some ways to manage [endometriosis], whether medical or surgical, definitely with some percentage of success and failure either way, said Nassif. But definitely, we need a lot of research for the future.Endometriosis involves the outgrowth of womb lining tissue in the pelvis or abdomen.OGPhoto via Getty ImagesA bare pipelineNeither Orilissa nor Myfembree are big sellers and dont seem to rate high on their makers priority lists.Three years after Orilissas approval, AbbVie tried to sell the womens health unit the drug was housed in, but the deal never materialized. Sales of the drug are no longer reported individually and are instead lumped in with other key products in AbbVies earnings report. The last time AbbVie reported Orilissas net revenue was for its 2021 fiscal year, when it recorded $139 million in U.S.sales.AbbVie did not provide additional details about the drugs development or sales when contacted by BioPharma Dive.In 2022, Japan-based Sumitomo Pharma agreed to acquire Myfembree developer Myovant Sciences for $2.9 billion. The drug is now sold by Sumitomo in Europe, while Pfizer jointly markets it in the U.S. and Canada.Pfizer doesnt report net sales, but lists Myfembree revenue as contributing to alliance revenue in financial filings.Myfembree is marketed for endometriosis pain by Pfizer and partner Sumitomo PharmaPermission granted by Sumitomo Pharma AmericaThe two drugs dont face much competition. Womens health company ObsEva had licensed a compound known as linzagolix from the Japan-based biotechnology company Kissei Pharmaceutical. However, the company terminated the deal and withdrew an approval application after the FDA informed it of deficiencies in its submission.ObsEva shut down operations earlier this year, one of several companies in womens health that had to refocus its research efforts recently.Pharma company Bayer has long sold a hormonal drug called Visanne for endometriosis-related pain, but the company has not submitted it for U.S. approval in that indication.We focus our research efforts on innovative options in areas of high unmet medical need, a Bayer spokesperson said in comments to BioPharma Dive. We regularly review our research and development portfolio to prioritize the advancement of the most promising projects.Working with researchers in the U.S. and U.K., Bayer also helped identify an inflammation gene that may be linked to endometriosis. While the discovery seemed to point to a possible non-hormonal drug target, further research did not end up moving forward into development, according to a Bayer spokesperson.Last year, Bayer shifted its focus away from womens health altogether. While new R&D could still yield womens health products, a Bayer executive told Reuters that the companys work in the field overall had fallen short of expectations.Elsewhere, Organon agreed in 2021 to acquire Forendo Pharma in a deal worth $75 million upfront, handing it a drug candidate targeting endometriotic lesions without affecting hormones. Other startups have emerged, including Gynica, FimmCyte and SLBST Pharma.Looking forwardWhile endometriosis research continues, Barburek argues that finding a non-hormonal target for treating the condition has to be a priority.We've got to mechanistically understand [endometriosis] so we know which levers to pull and which knobs to push, she said. So more research needs to go into the mechanistic side of it.There is some momentum. Alongside the $100 million the Biden administration pledged to womens health research, the Advanced Research Projects Agency for Health, or ARPA-H, also launched a sprint for womens health to fund health solutions for conditions that primarily or disproportionately affect women.Its not clear whether such efforts will remain a priority under President-elect Donald Trumps administration, however. Trump nominated Robert F. Kennedy Jr. to helm the Department of Health and Human Services, which oversees health agencies including the FDA. While Kennedy has made clear his views on vaccines and the pharmaceutical industry, his views on womens health research are less clear and his stance on abortion has been inconsistent.In a rally prior to the election, Trump said Kennedy is so into womens health, and would let him go wild on healthcare.Some experts worry state abortion bans might hinder recruitment into trials involving in vitro fertilization, or other conditions that might require documenting a womans medical history.I think, once you take that freedom of choice away from women and leave it in the hands of politicians, state or federal, it's not a great thing, Schott said. It's a devastating impact that's going to be further reaching than I think we even have the context to understand right now, and I do think that involves endometriosis.Amid such concerns, there is hope of progress in treating endometriosis. Yet, Baburek said, sustained interest and investment will require a concentrated effort to highlight, educate and draw attention to the issues or consequences of being a woman. '

Drug ApprovalAcquisition

08 Nov 2024

·www.globenewswire.com

RECORDATI: CONTINUED DOUBLE-DIGIT GROWTH IN THE FIRST NINE MONTHS OF 2024 - REVENUE +12.0%, EBITDA(1) +11.8%, ADJUSTED NET INCOME(2) +9.5%

Consolidated net revenue of € 1,743.1 million in the first nine months, +12.0% or +9.3% on a like-for-like basis(3) and at constant exchange rates (CER)EBITDA(1) of € 665.7 million, +11.8%, revenue margin of 38.2% Adjusted net income(2) of € 445.4 million, +9.5% Net income of € 338.4 million, +11.1% Free cash flow(4) at € 434.3 million, +€ 42.5 million vs prior yearNet debt(5) at € 1,317.3 million, just below 1.6x EBITDAFinancial targets for FY 2024 confirmed, excluding any potential contribution from Enjaymo® Global Rare Diseases business to be further strengthened by announced agreement with Sanofi to acquire the global rights to Enjaymo®; deal expected to close by end of 2024, subject to regulatory approvals Isturisa®approved in China for the treatment of adult patients with Cushing syndromeResolution to distribute an interim 2024 dividend of € 0.60 per shareApproval of a new share buy-back program to service the stock option and performance shares plans Milan, November 8th, 2024 – The Board of Directors of Recordati S.p.A. approved the Group’s Interim Report on 30th September 2024, representing additional voluntary financial reporting (6). The Report was prepared using the assessment, measurement and recognition criteria prescribed by international accounting standards (IFRS). The Group’s Interim Report dated 30th September 2024 will be available on 11th November at the company’s offices and on the company’s website (www.recordati.com) and can also be viewed on the authorized storage system 1Info (www.1Info.it). Rob Koremans, Chief Executive Officer of Recordati, commented: “During the first nine months, we delivered double-digit revenue and profit growth, reflecting the strong performance across the business with more patients benefiting from our therapies. These results reflect the continued commitment of all our people, who are instrumental to our success. With a positive outlook for the remainder of the year, we are well positioned to achieve our upgraded financial objectives for FY 2024. Together, we will continue to build on our momentum and create lasting value for our stakeholders. “I am also pleased to highlight our recent agreement with Sanofi to acquire the global rights to Enjaymo®, the only approved treatment option for patients with cold agglutinin disease. This transaction will reinforce our strong commitment to serving patients with rare diseases and is a strong strategic fit to our portfolio, bringing a product with a robust profile, supported by a strong team, with attractive financial contributions expected on both the top and bottom lines.” Financial highlights Consolidated net revenue for the first nine months of 2024 was € 1,743.1 million, up 12.0% versus the first nine months of 2023 or 9.3% on a like-for-like(3) basis at CER. This was driven by strong business momentum across both Specialty & Primary Care and Rare Diseases. The adverse FX impact for the first nine months of 2024 was € 35.9 million (-2.3%), mainly driven by the devaluation of the Turkish lira, particularly in the first and third quarters, which was compensated by high price inflation in Türkiye. Specialty & Primary Care revenue totaled € 1,094.4 million in the first nine months of 2024, growing 11.1% or 6.5% on a like-for-like(3) basis at CER (+2.6% excluding Türkiye). This reflects a particularly strong performance from the Urology franchise with 51.4% growth versus the previous year, driven by the double-digit growth of Eligard® and the € 82.9 million contribution of Avodart® and Combodart®/Duodart®(7) (versus € 3.8 million in the third quarter of 2023). The Cardiovascular and Gastrointestinal franchises remained resilient and delivered slight growth, while the Cough and Cold business reflected solid in-market performance in the context of a softer flu season as compared to the previous year.Rare Diseases revenue totaled € 605.6 million in the first nine months of 2024, up 14.1% as compared to the first nine months of 2023, or 14.5% at CER, driven by the key growth franchises of Oncology and Endocrinology which continue to show substantial further growth potential. The Endocrinology franchise achieved net revenue of € 239.4 million, an increase of 36.0% and reflecting the continued strong performance of Isturisa® and double-digit growth of Signifor®. The Oncology franchise achieved net revenue of € 175.9 million, an increase of 17.1%, driven by double-digit growth from both Qarziba® and Sylvant®. The Metabolic franchise achieved net revenue of € 190.2 million, a decrease of 6.9%, mainly due to generic competition for Carbaglu® in the US and EMEA, with growth in other international markets. Adjusted operating income(8) was € 539.5 million for the first nine months of 2024, up 9.7% over the previous year, and 31.0% of net revenue versus 31.6% in the same period last year. Operating income was € 504.1 million in the first nine months of 2024, up 14.9% over the first nine months of 2023, absorbing gross margin-related non-cash charges of € 28.1 million (versus € 47.2 million in first nine months of 2023), arising from the unwind of the fair value step up of the acquired rare oncology inventory. Non-recurring costs were € 7.3 million in the first nine months of 2024, versus € 5.4 million in the first nine months of 2023, which includes € 2.5 million related to the agreement with Sanofi for the global rights to Enjaymo®.EBITDA(1) was € 665.7 million for the first nine months of 2024, up 11.8% compared to the first nine months of 2023, with margin of 38.2% of net revenue, in line with the previous year. Strong revenue and operating leverage were, in part, offset by a reduction in adjusted gross profit margin due to the consolidation of Avodart® and Combodart®/ Duodart® and product mix.Financial expenses were € 62.3 million, up by € 13.3 million compared to the previous year, including € 2.8 million in FX losses (mostly unrealized, compared to losses of € 0.3 million in the first nine months of 2023) and € 3.9 million of net monetary losses from hyperinflation accounting (compared to a gain of € 1.8 million in the first nine months of 2023). Adjusted net income(2) was € 445.4 million, 25.6% of revenue, up by 9.5% compared to the same period of 2023, with higher adjusted operating income partially offset by an increase in financial expenses and a higher tax rate, following a statutory tax rate increase in some countries. Net income was € 338.4 million, 19.4% of revenue, an increase of 11.1% versus first nine months of 2023, with the higher tax rate and financing expenses offsetting the higher operating income. Free cash flow(4) was € 434.3 million for the first nine months of 2024, an increase of € 42.5 million versus the the first nine months of 2023, driven by higher EBITDA which was slightly offset by higher interests and income taxes paid. Net debt(5) as of 30th September 2024 was € 1,317.3 million, or leverage of just below 1.6x EBITDA(6), compared to net debt of € 1,579.4 million on 31st December 2023. Shareholders’ equity was € 1,876.1 million. Pipeline and Corporate Development The Isturisa® new drug application (NDA) was approved by the China National Medical Products Administration (NMPA) in September for the treatment of adult patients with Cushing syndrome. On October 4th, the Group announced an agreement with Sanofi to acquire the global rights to Enjaymo®, a biologic which is the only approved targeted product for the treatment of cold agglutinin disease (CAD), a rare B-cell lymphoproliferative disorder. In 2022, Enjaymo® was granted approval by the U.S. Food and Drug Administration (FDA), the European Commission (EC) and the Japanese Ministry of Health, Labor and Welfare. Enjaymo® generated approximately € 100 million in revenue over the last 12 months as of August 2024 and is expected to generate revenue in excess of € 150 million in FY 2025, with peak sales potential of € 250-300 million. The transaction is expected to be immediately accretive at the EBITDA level, with margin above the current Rare Diseases average as of 2025. Under the terms of the agreement, Recordati will make an upfront payment of US$ 825 million and additional commercial milestone payments of up to US$ 250 million if net sales reach certain thresholds at or above the top end of peak year sales expectations. The transaction is expected to close by the end of 2024, subject to regulatory clearances (see also press release issued on October 4th 2024). The deal will be funded by existing cash and new committed bank debt facilities. Business outlook Thanks to continued strong momentum, the Group is on track to deliver the targets for FY 2024 as adjusted upward on July 30th (excluding any potential contribution from Enjaymo®): Net revenue between € 2,300 and € 2,340 millionEBITDA(1) between € 845 and € 865 million; margin of +/- 37%Adjusted net income(2) between € 560 and € 580 million; margin of +/- 24.5%Minimal contribution expected from Enjaymo®, subject to timing of regulatory approvals Additional resolutions Interim dividend 2024 The Board of Directors passed a resolution to distribute an interim 2024 dividend to shareholders of € 0.60 (gross of tax withholdings) per share outstanding at the ex-dividend date, thus excluding treasury stock held in the Company’s portfolio on that date. The 2024 interim dividend will be payable as of 20th November 2024 (record date 19th November 2024), with coupon no. 34, to shareholders registered on 18th November 2024. The Independent Auditor EY S.p.A. has issued the opinion required by Art. 2433 – bis, paragraph 5 of the Italian Civil Code, which is available at the company’s offices. The Directors’ Report and Recordati S.p.A. financial statements as of 30th June 2024, based on which the latter’s Board of Directors resolved the distribution of the interim dividend, are available at the company’s office and website (www.recordati.com), and can also be viewed on the authorized storage system 1Info (www.1Info.it). Limited assurance on sustainability reporting In compliance with the Italian Legislative Decree No. 125/2024 – transposing in Italy the EU Directive No. 2022/2464 on Corporate Sustainability Reporting (so called “CSRD”) – the Board of Directors, upon proposal of the Board of Statutory Auditors, has resolved to integrate – starting from this financial year 2024 - the mandate for activities regarding the limited assurance attestation on sustainability reporting, set forth by the aforementioned decree, to Ernst & Young S.p.A., by extending to such activities the current engagement granted by the Shareholders Meeting held on 29th April 2020 with respect to the attestation of the non-financial disclosure. Appointment of the new Financial Reporting Officer pursuant to art.154-bis of TUF The Board of Directors has appointed, until revocation and upon favourable opinion of the Board of Statutory Auditors Niccolo Giovannini - VP Group Finance, reporting to Luigi La Corte, Group Chief Financial Officer - as Financial Reporting Officer pursuant to art.154-bis of TUF and art.25 of the Articles of Association. The appointment is effective as of today, following the approval of Group’s Interim Report on 30th September 2024. Approval of a new share buy-back program to service the stock option and performance shares plans Today, the Board of Directors has also approved the launch of a new share buy-back program under art. 5 of (EU) Regulation no. 596/2014 for a maximum of 1,500,000 ordinary shares with a maximum cash outlay of € 90,000,000. This implements the resolution adopted by the Shareholders’ meeting held on 22nd April 2024 to purchase Recordati ordinary shares in order to service current and future stock option/performance shares plans in favour of the Recordati Group’s management or share-based incentive plans that might be approved by the Company in the future. All details required by the applicable regulations on the launch of the share buy-back program - whose start is envisaged on 12th November 2024 until 15th April 2025, following the end of the current buyback programme envisaged by 11th November 2024 as announced on 9th May 2024 - will be included in a specific press release that will be issued according to law and to which reference is made. (1) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. (2) Net income excluding the amortization and write-down of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory pursuant to IFRS 3, and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects. (3) Pro-forma growth calculated excluding revenue of Avodart® and Combodart®/ Duodart® for both 2024 and 2023.(4) Total cash flow excluding financing items, milestones, dividends, purchases of treasury shares net of proceeds from exercise of stock options.(5) Cash and cash equivalents, less bank debts and loans, which include the measurement at fair value of hedging derivatives. (6) Please note that Italian Legislative Decree 25/2016, which implements Directive 2013/50/EU, no longer stipulates the submission of an interim management report, which was previously required in terms of paragraph 5 of Art. 154- ter of Italian Legislative Decree 58/1998.(7) Trademarks are owned by or licensed to the GSK group of companies. Transition of commercialization effectively concluded.(8) Net income before income taxes, financial income and expenses and non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. Conference Call Recordati will host a conference call today, November 8th at 4:00 p.m. CET (3:00 p.m. GMT) to present the results for the first nine months of 2024. The dial-in numbers for the conference call service are: Italy + 39 02 802 09 11, toll free 800 231 525UK + 44 1 212818004, toll free (44) 0 800 0156371USA +1 718 7058796, toll free (1) 1 855 2656958France +33 1 70918704Germany +49 6917415712 Participants are invited to dial in 10 minutes before conference time. If conference operator assistance is required to connect, please dial *0. The slides that will be referenced during the call will be available at www.recordati.com under Investors/Company Presentations. The audio conference live webcast will also be available at the following link Recordati is an international pharmaceutical group listed on the Italian Stock Exchange (XMIL: REC), with roots dating back to a family-run pharmacy in Northern Italy in the 1920s. We are uniquely structured to provide treatments across specialty and primary care, and rare diseases. Our fully integrated operations span clinical development, chemical and finished product manufacturing, commercialization and licensing. We operate in approximately 150 countries across EMEA, the Americas and APAC with over 4,450 employees. We believe that health is a fundamental right, not a privilege. Today, our purpose of “unlocking the full potential of life” aims at empowering individuals to live life to the fullest, whether addressing common health challenges or the rarest. Investor Relations Eugenia Litz +44 7824 394 750 investorelations@recordati.itGianluca Saletta +39 348 979 4876 investorelations@recordati.itMedia Relations ICR Healthcare US:Alexis Feinberg +1 203 939 2225 recordatiuspr@westwicke.com UK, Europe & Rest of World:Jessica Hodgson +44 7561 424 788recordati@consilium-comms.com This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from those forecast for a variety of reasons, most of which are beyond the Recordati group’s control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the activities of the Recordati Group, and, as such, it is not intended as a medical scientific indication or recommendation, or as advertising. RECORDATI GROUP Summary of the consolidated results,prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) INCOME STATEMENTFirst nine months 2024First nine months 2023Change %NET REVENUE1,743,0811,556,17412.0Cost of sales(556,171)(490,495)13.4GROSS PROFIT1,186,9101,065,67911.4Selling expenses(360,709)(345,506)4.4Research and development expenses(204,849)(182,239)12.4General and administrative expenses(110,014)(93,630)17.5Other income/(expenses), net(7,240)(5,553)30.4OPERATING INCOME504,098438,75114.9Financial income/(expenses), net(62,319)(49,054)27.0PRE-TAX INCOME441,779389,69713.4Income taxes(103,379)(85,205)21.3NET INCOME 338,400304,49211.1Adjusted gross profit (1)1,214,9861,113,1679.1Adjusted operating income (2)539,518491,6089.7Adjusted net income (3)445,361406,5669.5EBITDA (4)665,666595,57311.8Net income attributable to: Equity holders of the Parent338,400304,49211.1Non-controlling interests00n.s.EARNINGS PER SHARE (euro) Basic(5)1.6401.48110.7Diluted(6)1.6181.45611.1(1) Gross profit adjusted from impact of non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. (2) Net income before income taxes, financial income and expenses, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3.(3) Net income excluding amortization and write-downs of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3) and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects.(4) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3.(5) Earnings per share (EPS) are based on average shares outstanding during the respective period, 206.299.160 in 2024 and 205.421.410 in 2023. These amounts are calculated deducting treasury shares in the portfolio, the average of which was 2.825.996 shares in 2024 and 3.703.746 shares in 2023.(6) Diluted earnings per share is calculated by taking into account rights granted to employees.COMPOSITION OF NET REVENUEFirst nine months 2024First nine months 2023Change % Total revenue1,743,0811,556,17412.0 Italy258,631234,30410.4 International1,484,4501,321,87012.3 RECORDATI GROUP(€ thousands) Reconciliation of Net income to EBITDA(1) First nine months 2024First nine months 2023Net income338,400304,492Income taxes103,37985,205Financial income/(expenses), net62,31949,054Non-recurring expenses7,3445,369Non-cash charges from PPA inventory uplift28,07647,488Adjusted operating income(2)539,518491,608Depreciation, amortization and write-downs126,148103,965EBITDA(1)665,666595,573 Reconciliation of Net income to Adjusted Net income(3) First nine months 2024First nine months 2023Net income338,400304,492Amortization and write-downs of intangible assets(excluding software)100,15781,180Tax effect(22,619)(17,405)Non-recurring operating expenses7,3445,369Tax effect(1,943)(1,340)Non-cash charges from PPA inventory uplift28,07647,488Tax effect(7,019)(11,881)Monetary net (gain)/losses from hyperinflation (IAS29)3,900(1,759)Tax effect(935)422Adjusted net income(3)445,361406,566 (1) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3).(2) Net income before income taxes, financial income and expenses, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3).(3) Net income excluding amortization and write-downs of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3) and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects. RECORDATI GROUPSummary of the consolidated results, prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) ASSETS30.09.202431.12.2023Property, plant and equipment187,848178,657Intangible assets1,847,7041,938,197Goodwill789,123778,350Other equity investments and securities16,86521,555Other non-current assets13,87112,458Deferred tax assets92,56776,674TOTAL NON-CURRRENT ASSETS2,947,9783,005,891 Inventories410,107404,831Trade receivables474,514445,193Other receivables102,46699,401Other current assets26,78219,924Derivative instruments measured at fair value6,71011,079Cash and cash equivalents235,020221,812TOTAL CURRENT ASSETS1,255,5991,202,240TOTAL ASSETS4,203,5774,208,131 RECORDATI GROUPSummary of the consolidated results, prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) EQUITY AND LIABILITIES30.09.202431.12.2023 Share capital26,14126,141Share premium reserve83,71983,719Treasury shares(139,881)(127,970)Reserve for derivative instruments(2,180)(286)Translation reserve(301,627)(264,700)Other reserves61,53761,219Profits carried forward1,809,9971,636,451Net income338,400389,214Interim dividend0(117,396)Shareholders’ equity attributable to equity holders of the Parent1,876,1061,686,392Shareholders’ equity attributable to non-controlling interests00TOTAL SHAREHOLDERS’ EQUITY1,876,1061,686,392 Loans - due after one year1,264,8841,353,216Provisions for employee benefits21,40521,239Deferred tax liabilities134,488144,208TOTAL NON-CURRENT LIABILITIES1,420,7771,518,663 Trade payables276,907263,979Other payables198,213174,407Tax liabilities100,73867,110Other current liabilities4,6165,307Provisions for risks and charges19,24116,596Derivative instruments measured at fair value14,21219,993Loans - due within one year270,337355,752Short-term debts to banks and other lenders22,43099,932TOTAL CURRENT LIABILITIES906,6941,003,076TOTAL SHAREHOLDERS’ EQUITY AND LIABILITIES4,203,5774,208,131 RECORDATI GROUPSummary of consolidated results prepared in accordance with International Financial Reporting Standards (IFRS) (€ thousands) CASH FLOW STATEMENTFirst nine months 2024First nine months 2023OPERATING ACTIVITIES Net income338,400304,492Income taxes103,37985,206Net interest54,41848,158Depreciation of property, plant and equipment24,00321,577Amortization of intangible assets97,59182,304Write-downs4,55484Equity-settled share-based payment transactions10,1207,515Other non-monetary components41,06955,772Change in other assets and other liabilities(11,985)(20,538)Cash flow generated/(used) by operating activities before change in working capital661,549584,570Change in: - inventories(41,813)(31,681)- trade receivables(36,418)(73,753)- trade payables14,22330,082Change in working capital(64,008)(75,352)Interest received4,0073,923Interest paid(64,284)(50,314)Income taxes paid(82,634)(53,282)Cash flow generated/(used) by operating activities454,630409,545INVESTMENT ACTIVITIES Investments in property, plant and equipment(21,743)(17,998)Disposals of property, plant and equipment1,385329Investments in intangible assets(15,377)(345,597)Disposals of intangible assets2,351287Sale of non-current assets held for sale2,0003,000Cash flow generated/(used) by investment activities(31,384)(359,979)FINANCING ACTIVITIES Opening of loans144,872348,256Repayment of loans(320,185)(214,701)Payment of lease liabilities(8,311)(8,116)Change in short-term debts to banks and other lenders(71,722)(45,008)Dividends paid(130,220)(129,071)Purchase of treasury shares(78,087)(6,483)Sale of treasury shares52,74419,681Cash flow generated/(used) by financing activities(410,909)(35,442)Change in cash and cash equivalents12,33714,124Opening cash and cash equivalents221,812284,734Currency translation effect8713,422Closing cash and cash equivalents235,020302,280 DECLARATION BY THE FINANCIAL REPORTING OFFICERThe Financial Reporting Officer, Luigi La Corte, declares, pursuant to paragraph 2 of Article 154-bis of the Consolidated Law on Finance, that the accounting information contained in this press release corresponds to the Company’s documentation, books and accounting records.

Executive ChangeFinancial StatementDrug ApprovalAcquisition

11 Sep 2024

·www.businesswire.com

Pfizer Highlights Diverse Oncology Portfolio and Combination Approaches at ESMO 2024

NEW YORK--( BUSINESS WIRE )--Pfizer Inc. (NYSE: PFE) continues to showcase potential practice-changing research and next-generation candidates across its robust Oncology portfolio at the European Society for Medical Oncology (ESMO) Congress 2024, being held September 13-17 in Barcelona. Data from more than 50 company-sponsored, investigator-sponsored and collaborative research abstracts, including more than 10 oral and mini-oral presentations, will be presented across the company’s tumor areas and core scientific modalities, as well as a potential treatment for a cancer-related condition. “ At this year’s ESMO, we are looking forward to demonstrating our progress toward delivering next-generation biologics and novel combinations that have the potential to be new standards of care for patients,” said Chris Boshoff, Chief Oncology Officer and Executive Vice President, Pfizer. “ Our key data presentations highlight our scientific leadership in developing targeted therapies, including small molecules and antibody-drug conjugates, across our core tumor areas, including breast, bladder and thoracic cancers.” “ At ESMO, Pfizer will share important data highlighting our commitment to transforming outcomes for patients living with lung cancer, including longer-term follow-up results from the BRAFTOVI + MEKTOVI PHAROS study in BRAF V600E-mutated metastatic non-small cell lung cancer,” said Karin Tollefson, Chief Oncology Medical Officer, Pfizer. “ We are also looking forward to sharing progress on our industry-leading pipeline of new molecules, including encouraging early results for two novel, investigational antibody-drug conjugates and preliminary data on a novel combination of Pfizer’s next-generation CDK inhibitors.” Key research includes a late-breaking presentation of updated results from the pivotal Phase 2 PHAROS* study of BRAFTOVI (encorafenib) + MEKTOVI (binimetinib) in patients with BRAF V600E-mutant metastatic non-small cell lung cancer (mNSCLC). Longer-term efficacy and safety data will be presented, following the initial primary overall response results (ORR) that supported the FDA approval for BRAFTOVI + MEKTOVI in this indication in 2023 and the recent approval by the European Commission in August 2024. Further, Pfizer will share updated data from the safety lead-in of the ongoing Phase 3 BREAKWATER trial, showing antitumor activity of BRAFTOVI + cetuximab + FOLFIRI in patients with untreated BRAF V600E-mutant metastatic colorectal cancer (mCRC) in a mini-oral presentation. Additionally, Pfizer will present a late-breaking Proffered Paper Presentation on the Phase 2 efficacy and safety results for its GDF-15 inhibitor, ponsegromab, in patients with cancer-associated cachexia, highlighting the company’s commitment to improving the treatment journey for people living with cancer. Cancer cachexia is a common, life-threatening wasting condition characterized by severe weight loss. The condition affects patients with advanced cancers and can greatly impact a patient’s ability to tolerate cancer treatment and quality of life. Despite its severity, there are no FDA-approved treatments for cachexia. i,ii Pfizer will also present early clinical-stage research for a number of priority pipeline areas, including encouraging Phase 1 results of the potential first-in-class antibody-drug conjugate (ADC) candidate SGN-PDL1V (PF-08046054) in NSCLC and head and neck squamous cell carcinoma (HNSCC); initial data for the investigational ADC disitamab vedotin in combination with KEYTRUDA ® (pembrolizumab) in human epidermal growth factor receptor 2 (HER2)-expressing locally advanced or metastatic urothelial cancer (la/mUC); and the first data combining atirmociclib, our highly-selective cyclin-dependent kinase 4 (CDK4) inhibitor (CDK4i), with a novel CDK2 inhibitor (CDK2i) in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) from a Phase 1 dose-escalation study. Key ESMO Presentations Genitourinary Cancer PADCEV + KEYTRUDA**: additional analysis from the pivotal EV-302 trial continues to support the combination as a new standard of care for patients with previously untreated la/mUC. An exploratory analysis shows PADCEV + KEYTRUDA ® showed consistent progression free survival (PFS), overall survival (OS), and ORR versus chemotherapy regardless of Nectin-4 or PD-L1 expression. Disitamab Vedotin: preliminary efficacy and safety data for disitamab vedotin in combination with KEYTRUDA highlights Pfizer’s continued commitment to developing novel therapeutics to meet the needs of patients with bladder cancer. Results from the safety run-in of the ongoing Phase 2 trial showed encouraging early efficacy and a safety profile consistent with previously presented data in treatment-naive patients with HER2-expressing la/mUC. Thoracic Cancer SGN-PDL1V (PF-08046054): encouraging Phase 1 results will be presented for PDL1V, a novel, investigational vedotin ADC directed to PD-L1-expressing solid tumors. Data from the dose-escalation and dose optimization cohorts of the ongoing Phase 1 study show PDL1V as monotherapy was generally well tolerated with no unexpected adverse events, and encouraging antitumor activity was observed in patients with heavily pretreated NSCLC and HNSCC. Breast Cancer Atirmociclib (PF-07220060) + PF-07104091 : initial data from a dose-escalation study evaluating the innovative combination of atirmociclib, a potential first-in-class CDK4-selective inhibitor, with PF-07104091, a novel CDK2-selective inhibitor, showed a manageable safety profile and encouraging efficacy in patients with heavily pretreated HR+/HER2- breast cancer. These early results highlight the potential of Pfizer's strategy to advance atirmociclib as a future CDK inhibitor backbone therapy that may address treatment resistance with first generation CDK4/6i, subject to clinical success and regulatory approval. The CDK4i+2i combination is continuing to be explored in an ongoing Phase 1b/2 dose escalation and dose expansion study (NCT05262400). Additional information on the Pfizer-sponsored abstracts, including date and time of presentation, follow in the chart below. Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ESMO, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries starting September 16, 2024. BREAST CANCER Mini Oral Presentation (Abstract 618MO) Saturday, September 14, 2:45 PM-4:15 PM CEST Phase 1b/2 first-in-class novel combination trial of next generation CDK4-selective inhibitor PF-07220060 and next generation CDK2-selective inhibitor PF-07104091 in HR+ HER2- metastatic breast cancer and advanced solid tumors Yap et al Poster Presentation (Abstract 413P) Monday, September 16, 9:00 AM-5:00 PM CEST Longitudinal circulating tumor DNA (ctDNA) dynamics in Phase 1/2a study of the first-in-class CDK4-selective inhibitor, PF-07220060, in combination with endocrine therapy in patients with HR+/HER2− metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitors Yap et al Poster Presentation (Abstract 359P) Monday, September 16, 9:00 AM-5:00 PM CEST Overall survival of palbociclib (PAL) + endocrine therapy (ET) in Japanese patients with hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the 1st line (1L) or 2nd line (2L) setting: A multicenter observational study Nakayama et al Poster Presentation (Abstract 354P) Monday, September 16, 9:00 AM-5:00 PM CEST Synergistic preclinical efficacy through combination of the CDK4 and CDK2 selective inhibitors, PF-07220060 and PF-07104091, respectively, in HR+ HER2- breast cancer Anders et al Poster Presentation (Abstract 356P) Monday, September 16, 9:00 AM-5:00 PM CEST Real-world effectiveness in subgroups of palbociclib + endocrine therapy in HR+/HER2- ABC patients: Interim Results of the PERFORM study Pfeiler et al EARLY PIPELINE Oral Presentation, Proffered Paper (Abstract 607O) Friday, September 13, 4:00 PM-5:30 PM CEST Interim results of a Phase 1 study of SGN-PDL1V (PF-08046054) in patients with PDL1-expressing solid tumors Oliva Bernal et al GASTROINTESTINAL CANCER Mini Oral Presentation (Abstract 515MO) Saturday, September 14, 2:45 PM-4:15 PM CEST Encorafenib + cetuximab (EC) + FOLFIRI for BRAF V600E-mutant metastatic colorectal cancer (mCRC): updated results from the BREAKWATER safety lead-in (SLI) Tabernero et al GENITOURINARY CANCER Mini Oral Presentation (Abstract 1966MO) Sunday, September 15, 8:30 AM-10:00 AM CEST EV-302: Exploratory analysis of nectin-4 expression and response to 1L enfortumab vedotin (EV) + pembrolizumab (P) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC) Powles et al Poster Presentation (Abstract 1968P) Sunday, September 15, 9:00 AM-5:00 PM CEST Study EV-103 dose escalation/cohort A (DE/A): 5y follow-up of first-line (1L) enfortumab vedotin (EV) + pembrolizumab (P) in cisplatin (cis)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC) Rosenberg et al Poster Presentation (Abstract 2001P) Sunday, September 15, 9:00 AM-5:00 PM CEST Epidemiology and treatment patterns of patients with locally advanced or metastatic urothelial cancer in France: a non-interventional database study Joly et al Poster Presentation (Abstract 1638P) Sunday, September 15, 9:00 AM-5:00 PM CEST Enzalutamide (ENZA) with or without leuprolide in patients (pts) with high-risk biochemically recurrent (hrBCR) prostate cancer (PC): EMBARK post hoc analysis by age Shore et al Poster Presentation (Abstract 1626P) Sunday, September 15, 9:00 AM-5:00 PM CEST Incidence of hematologic toxicities in the homologous recombination repair (HRR)-deficient population of the TALAPRO-2 trial and their potential association with germline vs somatic origin of HRR gene alterations Azad et al Poster Presentation (Abstract 1637P) Sunday, September 15, 9:00 AM-5:00 PM CEST Efficacy of talazoparib and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with androgen receptor pathway inhibitors (ARPI) or docetaxel – post hoc analysis from both cohorts in TALAPRO-2 study Agarwal et al Poster Presentation (Abstract 1633P) Sunday, September 15, 9:00 AM-5:00 PM CEST Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): TALAPRO-2 (TP-2) China cohort Zeng et al Mini Oral Presentation (Abstract 1967MO) Sunday, September 15, 8:30 AM-10:00 AM CEST Preliminary efficacy and safety of disitamab vedotin (DV) with pembrolizumab (P) in treatment (Tx)-naive HER2-expressing, locally advanced or metastatic urothelial carcinoma (la/mUC): RC48G001 Cohort C Galsky et al MELANOMA Poster Presentation (Abstract 1071TiP) Saturday, September 14, 9:00 AM-5:00 PM CEST Phase 1 study of the investigational CD228 x 4-1BB costimulatory antibody Anticalin bispecific SGN-BB228 (PF-08046049) in advanced melanoma and other solid tumors Dummer et al SUPPORTIVE AND PALLIATIVE CARE Oral Presentation, Proffered Paper (Abstract LBA82) Saturday, September 14, 2:45 PM-4:25 PM CEST Efficacy and safety of ponsegromab, a first-in-class, monoclonal antibody inhibitor of growth differentiation factor-15, in patients with cancer cachexia: A randomized, placebo-controlled, Phase 2 study Crawford et al THORACIC CANCER Mini Oral Presentation (Abstract LBA56) Saturday, September 14, 10:15 AM-11:45 AM CEST Updated efficacy and safety from the Phase 2 PHAROS study of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC) Riely et al Poster Presentation (Abstract 1398TiP) Saturday, September 14, 9:00 AM-5:00 PM CEST Be6A Lung-01, a Phase 3 study of sigvotatug vedotin (SV), an investigational antibody-drug conjugate (ADC) versus docetaxel in patients (pts) with previously treated non-small cell lung cancer (NSCLC) Peters et al Poster Presentation (Abstract 1279P) Saturday, September 14, 9:00 AM-5:00 PM CEST First-line lorlatinib vs crizotinib in Asian patients with ALK+ non-small cell lung cancer (NSCLC): 5-year outcomes from the CROWN study Wu et al *The PHAROS trial is conducted with support from Pierre Fabre. **Pfizer and Astellas have a clinical collaboration agreement with Merck to evaluate the combination of PADCEV ® and KEYTRUDA ® in patients with previously untreated metastatic urothelial cancer. Prescribing Information for Pfizer Medicines Please see full Prescribing Information for PADCEV. Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including antibody-drug conjugates (ADCs), small molecules, bispecific antibodies and other immunotherapy biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs that help people with cancer globally live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . DISCLOSURE NOTICE: The information contained in this release is as of September 11, 2024. The Company assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology, Pfizer’s Oncology portfolio of marketed and investigational therapies, including combinations, and an investigational therapy for a cancer-related condition; expectations for our product pipeline, in-line products and product candidates, including their potential benefits, clinical trial results and other developing data; potential breakthrough, best- or first-in-class or blockbuster status or expected market entry of our medicines; and other statements about our business, operations and financial results that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risk and uncertainties include, among other things, uncertainties regarding the commercial success of Pfizer’s oncology portfolio; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim and preliminary data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications, biologics license applications and/or emergency use authorization applications may be filed in any jurisdictions for any potential indication for Pfizer’s product candidates; whether and when any such applications that may be pending or filed for any of Pfizer’s product candidates may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether any such product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of Pfizer’s products or product candidates, including development of products or therapies by other companies; manufacturing capabilities or capacity; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “ Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com . i Cleveland Clinic. Cachexia (Wasting Syndrome). Cachexia (Wasting Syndrome): Symptoms & Treatment (clevelandclinic.org) . Accessed September 3, 2024. ii Lisa Martin, Michael B. Sawyer, Cancer Cachexia: Emerging Preclinical Evidence and the Pathway Forward to Clinical Trials, JNCI: Journal of the National Cancer Institute , Volume 107, Issue 12, December 2015, djv322, https://doi-org.libproxy1.nus.edu.sg/10.1093/jnci/djv322 Category: Pipeline

Clinical ResultPhase 1Phase 2Phase 3ADC

100 Deals associated with Leuprolide Acetate

External Link

KEGG	Wiki	ATC	Drug Bank
D00989	Leuprolide Acetate	L02AE02	DBSALT000105

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Bulbo-Spinal Atrophy, X-Linked	JP	Takeda Pharmaceutical Co., Ltd.	28 Aug 2017
Hormone-dependent prostate cancer	AU	Mundipharma Pty Ltd.	26 Nov 2003
Uterine Neoplasms	CN	Takeda Pharmaceutical Co., Ltd.	15 Mar 2000
Breast Cancer	JP	Takeda Pharmaceutical Co., Ltd.	09 Oct 1996
Uterine Fibroids	JP	Takeda Pharmaceutical Co., Ltd.	09 Oct 1996
Puberty, Precocious	US	AbbVie Endocrine, Inc.	16 Apr 1993
Endometriosis	US	AbbVie Endocrine, Inc.	22 Oct 1990
Leiomyoma	US	AbbVie Endocrine, Inc.	22 Oct 1990
Prostatic Cancer	US	AbbVie Endocrine, Inc.	26 Jan 1989
Advanced Prostate Carcinoma	US	AbbVie Endocrine, Inc.	09 Apr 1985

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2-negative breast cancer	Phase 3	US	TOLMAR, Inc.	28 Dec 2022
HER2-negative breast cancer	Phase 3	AR	TOLMAR, Inc.	28 Dec 2022
HER2-negative breast cancer	Phase 3	BR	TOLMAR, Inc.	28 Dec 2022
HER2-negative breast cancer	Phase 3	PR	TOLMAR, Inc.	28 Dec 2022
Premenopausal breast cancer	Phase 3	JP	Takeda Pharmaceutical Co., Ltd.	01 Apr 2012
Neoplasm Metastasis	Phase 3	FR	Astellas Pharma, Inc.	01 Jul 2011
Choroid Plexus Papilloma	Phase 3	US	AbbVie, Inc.	01 Dec 2008
Choroid Plexus Papilloma	Phase 3	PR	AbbVie, Inc.	01 Dec 2008
Locally Advanced Prostate Carcinoma	Phase 3	BE	Astellas Pharma, Inc.	01 Mar 2006
Locally Advanced Prostate Carcinoma	Phase 3	CZ	Astellas Pharma, Inc.	01 Mar 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ENDO2024	Not Applicable	LH concentrations	62	Subcutaneous Leuprolide Acetate 45 mg	rhjwkajfhm(suziczdifh) = bbqiwysjww dhdmoancxe (dnbpaaxqis )	Positive	01 Jun 2024
AUA2024	Not Applicable	Advanced Prostate Carcinoma	-	Leuprolide	xezninsqbf(zdhfdubwca) = lcgitjmoib gvdcejnqhg (zkqtkrpcrv )	-	01 May 2024
				Relugolix	xezninsqbf(zdhfdubwca) = enzrzsbrya gvdcejnqhg (zkqtkrpcrv )
NCT03572387 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	14	ATRA+5-AZA ('Early' 5-AZA+ATRA)	jekggngvhe(miabinvznh) = ontdggebpf afixtunzmr (vvfzmbkscp, dmbtlaedfm - fntmdgkzia) View more	-	30 Apr 2024
				ATRA+5-AZA ('Delayed' 5-AZA+ATRA)	jekggngvhe(miabinvznh) = jlelzfrpjk afixtunzmr (vvfzmbkscp, vlqjqjexkc - pqdpswwzrr) View more
Pubmed \| J Pediatr Endocrinol Metab	Not Applicable	Puberty, Precocious	28	3-month leuprorelin acetate (11.25 mg)	nabbydgohd(ywxnmcchij) = akxsyjaqbu ehpyoirfoz (ywzyiikena ) View more	Positive	29 Jan 2024
NCT03902951 (SATURN, ASCO_GU2024) Manual	Phase 2	Metastatic Prostate Carcinoma	28	leuprolide+abiraterone acetate+ prednisone+ apalutamide+ SBRT	qyjbdbenno(ikgrfsczhs) = zcsoswfvpn vaworamztd (txkzwcdfuj, 32 - 67) View more	Positive	25 Jan 2024
NCT01674140 (S1207 \| SWOG S1207 \| e3, CTgov)	Phase 3	Hormone receptor positive HER2 negative breast cancer	1,939	placebo+letrozole+tamoxifen citrate+exemestane+leuprolide acetate+goserelin acetate+anastrozole (Placebo)	qgptpbmwse(ivssxjbmvh) = divuuqfebw itrzqzqbmr (pvgtsvyeyk, brrsxegoyk - tckaazavwp) View more	-	20 Dec 2023
				Everolimus (Everolimus)	qgptpbmwse(ivssxjbmvh) = gfihyqnxdr itrzqzqbmr (pvgtsvyeyk, nwzduyoish - wglxhfsrot) View more
THU195 (ENDO2023)	Not Applicable	Puberty, Precocious	62	Leuprolide Acetate (Non-overweight children)	bunjhxkjvf(uoxwhgvsgz) = wljhidzpeb vuwcspznai (uziulyghpn ) View more	Positive	05 Oct 2023
				Leuprolide Acetate (Overweight children)	bunjhxkjvf(uoxwhgvsgz) = hwphermwhi vuwcspznai (uziulyghpn ) View more
ESPE2023	Not Applicable	Puberty, Precocious	582	Leuprolide acetate 11.25mg 3-month formulation	jibmtdzjkh(cyowhmhadt) = vcfzrithcl ntoqjurltj (yhlmyozfxo, 2.27–9.87) View more	-	21 Sep 2023
ESPE2023	Not Applicable	Puberty, Precocious \| Familial Hypophosphatemic Rickets	-	Leuprolide acetate	fqbjyrgpos(dxlrcbwoaw) = jobguhfnpu svzptyjqgl (yzjwtpupzx ) View more	Positive	21 Sep 2023
				Burosumab	fqbjyrgpos(dxlrcbwoaw) = szejhclgbq svzptyjqgl (yzjwtpupzx ) View more
SGO	Not Applicable	Granulosa Cell Tumor	-	Leuprolide acetate	kkubnljxqu(wiahbizmzo) = nqtiaetuye dwjntxdcdq (rqjyfoolit, 54–82)	-	01 Sep 2023

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