Phentermine Hydrochloride

TWYMEEG sales in Japan for the last quarter (April-June) grew 23% over the prior quarter, in line with Sumitomo Pharma’s FY 2023 forecast1, which would represent a 90% increase over the prior year sales Company actively pursuing additional financing to initiate ALD Phase 2 Proof-of-Concept (POC) studies and execute its rare diseases strategy As of June 30, 2023, cash and cash equivalents were EUR 7.6 million (USD 8.2 million)2; cash runway through Q2 2025, assuming full drawdown of the existing equity-linked financing facility with IRIS LYON, France--(BUSINESS WIRE)-- Regulatory News: POXEL SA (Euronext: POXEL - FR0012432516) (Paris:POXEL), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, today provided a corporate update and announced its cash position and revenue for the second quarter and first half of 2023. Thomas Kuhn, Chief Executive Officer of Poxel, stated: “During this past semester, we have diligently worked to improve our financial flexibility, and this has been a success through the combination of the restructuring of our existing debt obligations and the setup of a new equity-linked financing with IRIS. Now that our financial visibility extends through Q2 2025, we can concentrate on our strategy, which includes the launch of Phase 2 proof-of-concept studies in rare diseases, starting with adrenoleukodystrophy, subject to additional financing. The recent trajectory of TWYMEEG sales has also been key in the restructuring of our debt. Sumitomo Pharma, our partner commercializing TWYMEEG in Japan, recently reported gross sales for its Q1 2023, which shows a 23% increase over the prior quarter, and gives us confidence in the ability to meet Sumitomo Pharma’s FY 2023 forecast.” Commercial Update TWYMEEG® (Imeglimin) For the quarter ended June 2023, TWYMEEG gross sales in Japan increased 23% to JPY 1.16 billion (EUR 7.4 million)2 over the prior quarter sales of JPY 0.9 billion (EUR 6.2 million)2 as reported by Sumitomo Pharma (Sumitomo). The sales in recent quarters have accelerated due to the end of initial launch year restrictions for TWYMEEG in September 2022, which limited new products to two weeks prescriptions, and Sumitomo’s commercial efforts to leverage TWYMEEG’s potential. Thanks to its unique mechanism of action and safety profile, TWYMEEG can be used both as a monotherapy and in combination with other treatments, such as DPP4 inhibitors, the most prescribed treatment for Japanese Type-2-Diabetes patients, and SGLT2 inhibitors, which are growing strongly in Japan, and contributes to the increase in sales. These factors have resulted in a much higher increase in demand for TWYMEEG than expected by Sumitomo, and thus inventories are temporarily tight. Sumitomo is working diligently to increase the production and secure inventory capacity to meet this increasing demand. For its FY 2023, Sumitomo announced a forecast for TWYMEEG of JPY 4.2 billion1 (EUR 28.9 million)3 which would represent a 90% increase over FY 2022 TWYMEEG gross sales. For the Sumitomo FY 2023, as a conservative assumption in line with Sumitomo’s forecast, Poxel expects to receive 8% royalties on TWYMEEG net sales. As part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of TWYMEEG, independent of the level of sales. During Sumitomo FY 2024 (ending March 31, 2025), Poxel expects TWYMEEG net sales in Japan to reach at least JPY 5 billion (EUR 34.4 million)3 entitling Poxel to receive 10% royalties on all TWYMEEG net sales (on which the first 8% will still be paid to Merck Serono) and a sales-based payment of JPY 500 million (EUR 3.4 million)3. Beyond Sumitomo FY 2024, Poxel expects to receive escalating double-digit royalties as well as additional sales-based payments upon achievement of contractually based sales thresholds. As per the debt restructuring agreements established with its lenders in March, positive net royalties and sales-based payments will be directed to Poxel debt reimbursement until the loans are fully repaid (which Poxel expects in Q2 2029, at the latest). After this time, subsequent net royalties and sales-based payments will revert back to Poxel. As part of the Sumitomo’s ongoing efforts to communicate TWYMEEG’s unique mechanism of action and safety profile, 9 abstracts based on Imeglimin Phase 2b and Phase 3 clinical trials were accepted for oral presentations at the 66th Annual Meeting of the Japanese Diabetes Society (JDS), held in Kagoshima, Japan, May 11-13, 2023. A Phase 4, 52-week, Open-label, Long-Term Study of Imeglimin in Japanese Type 2 Diabetic Patients with Renal Impairment is currently ongoing in Japan to strengthen TWYMEEG pro this key subpopulation, and top line results are expected in 2024. For territories not covered by its agreement with Sumitomo, Poxel is in ongoing discussions with various potential partners for Imeglimin, including in India, where local companies have recently received approval and have launched Imeglimin. At the date of this press release, no agreement has been established, and Poxel continues to be committed to asserting its rights in connection with its assets. Rare metabolic diseases In adrenoleukodystrophy (ALD), PXL770 and PXL065 are prepared to advance, subject to additional financing, into two Phase 2 biomarker proof-of-concept (POC) clinical trials in male patients with adrenomyeloneuropathy (AMN), the most common ALD subtype. The 12-week studies will evaluate pharmacokinetics, safety and potential for efficacy based on relevant disease biomarkers, such as the effect on very long chain fatty acids (VLCFA), the characteristic plasma marker of the disease. In line with its mission, Poxel aims to bring therapeutic options to treat ALD, and supported the Alex Leukodystrophy Charity during their Community Weekend, which took place from April 28th to May 1st in Birmingham, England. This event brings together leukodystrophy sufferers and their families, alongside doctors, researchers and scientists from around the world to discuss leukodystrophies. On June 23rd and 24th, Poxel participated virtually at the ULF (United Leukodystrophy Foundation) Scientific Symposium and Family Conference in Itasca, Illinois, USA. Sophie Bozec, Poxel Senior Vice President, R&D Pharmacology and Scientific Communication presented Poxel’s status and plans for PXL770 and for the deuterium-modified TZD platform, using PXL065, based on robust scientific rationale and a complete preclinical package. Corporate Update On June 21st, the Company held its ordinary annual and extraordinary general meeting of shareholders. The shareholders approved all the resolutions that were recommended by the Board of Directors, including the renewal of Mr. Khoso Baluch, Mr. Thomas Kuhn et Ms. Pascale Boissel as Board members. During the first semester, the Company pursued its corporate savings plan initiated in 2022 aiming at adapting the Company’s resources to the current clinical development plan while preserving critical resources and competencies. At the date of this press release, there are 16 employees at Poxel compared to 37 at the end of December 2022. At the end of June, Elizabeth Woo, Senior Vice President, Investor Relations & Communication, left the Company to pursue other endeavours. Significant Events after the Period On July 5th, Poxel was chosen as the winner of the 2023 edition of the I-nov contest for its program in ALD. Financed by the French State via the France 2030 plan, the prize of this contest includes a grant which will contribute in part4 in the financing of the two phase IIa proof-of-concept clinical studies for PXL770 and PXL065, which are ready to be launched, subject to additional funding, which the Company is actively working on. In July 2023, the European Patent Office (EPO) granted Poxel a new patent for PXL065, a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone, which describes a specific form of PXL065 with unique properties. This recently issued patent provides additional protection through 2041, with the potential for an additional 5 years through patent term extension. In 2022, Poxel had been granted the same patent for PXL065 from the US Patent Office. Second Quarter and First Half 2023 Cash and Cash equivalents As of June 30, 2023, cash and cash equivalents were EUR 7.6 million (USD 8.2 million), as compared to EUR 13.1 million (USD 14.0 million) as of December 31, 2022. Net financial debt (excluding IFRS16 impacts and derivative debts) was EUR 37.7 million as of June 30, 2023, as compared to EUR 29.5 million as of December 31, 2022. EUR (in thousands) Q2 2023 Q4 2022 Cash 7,599 13,058 Cash equivalents - - Total cash and cash equivalents 7,599 13,058 Unaudited data On March 23, 2023, the Company finalized agreements with its lenders to restructure its existing debt facility and established a new equity-linked financing with IRIS, including an initial drawdown of EUR 3.5 million. Based on: this cash position on June 30, 2023, the full drawdown of the tranches available under the equity-linked financing with IRIS, the current research and development plan, excluding the initiation of Phase 2 clinical POC biomarker studies for PXL065 and PXL770 in AMN, and a strict control of its operating expenses, Poxel expects that its resources will be sufficient to fund its operations and capital expenditure requirements through Q2 2025. The full drawdown of the IRIS equity linked facility can be made subject to certain conditions described in the Company’s Universal Registration Document. At the date of this press release and only based on the tranches already drawn5 or fully available6, the Company expects that its resources will be sufficient to fund its operations and capital expenditure requirements until January 2024. Second Quarter and First Half 2023 Revenue Poxel reported revenue of EUR 955 thousand for the six months ended June 30, 2023, as compared to EUR 83 thousand revenue during the corresponding period in 2022. Revenue for the first half of 2023 reflects JPY 148 million (EUR 955 thousand) of royalty revenue from Sumitomo Pharma which represents 8% of TWYMEEG net sales in Japan. Based on the current forecast, Poxel expects to receive 8% royalties on TWYMEEG net sales in Japan through the Sumitomo fiscal year 2023 (April 2023 to March 2024). As part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of Imeglimin, independent of the level of sales. EUR (in thousands) Q1 2023 Q2 2023 H1 2023 Q1 2022 Q2 2022 H1 2022 3 months 3 months 6 months 3 months 3 months 6 months Sumitomo Pharma Agreement 449 506 955 32 51 83 Other - - - - Total revenues 449 506 955 32 51 83 Unaudited data Planned Presentation and Participation at the Following Upcoming Event 23rd edition of the European MidCap Event, Paris, September 21-22 Next Financial Press Release: 2023 First Half Results, on September 26, 2023 About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R-pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770, a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan, China, and eleven other Asian countries. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. Glossary You will find below a list of words and/or expressions that are used in this press release or in Poxel’s communication, with the aim to bring clarification and transparency: Sumitomo Pharma fiscal year runs April to March. As an example, Fiscal Year 2022 is April 1, 2022 through March 31, 2023. TWYMEEG royalties: As per the Sumitomo’s agreement, Poxel is entitled to receive royalties from the sales of TWYMEEG (Imeglimin) in Japan TWYMEEG royalties are calculated on net sales, while Sumitomo Pharma communicates only TWYMEEG gross sales. Poxel entitled to receive escalating royalties of 8-18% on TWYMEEG net sales from Sumitomo Pharma. Positive net royalties: refers to royalties Poxel receives from TWYMEEG net sales after paying Merck Serono the first 8%, once Poxel starts to receive 10% royalties upon TWYMEEG net sales exceeding JPY 5 billion in a fiscal year. 1 As per Sumitomo Pharma FY23 forecast of JPY 4.2 billion published on May 15, 2023. 2 Converted at the exchange rate as of June 30, 2023. 3 Converted at the exchange rate as of March 31, 2023. 4 Up to 45% of the estimated eligible costs. 5 Since March 31, 2023, 2 additional tranches of EUR 600,000 each have been drawn in May and July. 6 At the date of this press release, the amount of redeemable bonds owned by IRIS is EUR 5,980,000, and the Group has the ability to drawdown EUR 1 020 000 under the additional tranches.

Approval is based on the Phase 3 MAGNITUDE study, a prospectively designed precision medicine study including the largest population of BRCA-positive patients in combination trials to date with metastatic castration-resistant prostate cancer (mCRPC) AKEEGA ™ plus prednisone significantly improved radiographic progression-free survival compared to abiraterone acetate plus prednisone (AAP) in patients with BRCA-positive mCRPC HORSHAM, Pa., Aug. 11, 2023 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food & Drug Administration (FDA) has approved AKEEGA ™ (niraparib and abiraterone acetate), the first-and-only dual action tablet combining a PARP inhibitor with abiraterone acetate, given with prednisone, for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive mCRPC, as detected by an FDA-approved test.1 "As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation," said Kim Chi, M.D.*, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the Phase 3 MAGNITUDE study. "We prospectively designed the MAGNITUDE study to identify the subset of patients most likely to benefit from targeted treatment with AKEEGA and to help us understand how we can potentially achieve better health outcomes for patients." Prostate cancer is one of the most common cancers in the U.S., with an estimated 288,300 new cases and nearly 35,000 deaths expected in 2023.2 Approximately 10 to 15 percent of patients with mCRPC have BRCA gene alterations. Patients with BRCA-positive mCRPC are more likely to have aggressive disease and may experience poor outcomes and a shorter survival time.3,4,5,6,7 "The approval of AKEEGA brings an important treatment option to patients with prostate cancer as they consider their road ahead, and it also highlights the importance of genetic testing and precision medicine for this disease," said Shelby Moneer, MS, CHES**, Vice President of Patient Programs and Education, ZERO Prostate Cancer. "All individuals diagnosed with prostate cancer should consider genetic testing, especially those from racial and ethnic minority groups who tend to have worse cancer outcomes. This is imperative to close the racial and ethnic disparities in prostate cancer health outcomes." The FDA approval is based on positive results from the randomized, double-blind, placebo-controlled multi-center Phase 3 MAGNITUDE study. In BRCA-positive patients treated with the combination AKEEGA ™ plus prednisone, a statistically significant 47 percent risk reduction was observed for radiographic progression-free survival (rPFS) (Hazard ratio [HR], 0.53; p=0.001). At the second interim analysis (IA2), with median follow-up at 24.8 months in the BRCA-positive subgroup, rPFS by central review demonstrated a consistent trend favoring AKEEGA ™ plus prednisone, with a median rPFS of 19.5 months compared with 10.9 months for placebo and AAP (HR, 0.55 [95 percent confidence interval (CI), 0.39-0.78]). Additionally, there was an observed improvement in the secondary endpoints of time to symptomatic progression (TSP) (HR, 0.54 [95 percent CI, 0.35-0.85]) and time to initiation of cytotoxic chemotherapy (TCC) (HR, 0.56 [95 percent CI, 0.35-0.90]) for AKEEGA ™ plus prednisone compared with AAP alone, supported by a trend towards improvement in overall survival (OS) (HR, 0.88 [95 percent CI, 0.58-1.34]). The observed safety profile of the combination of AKEEGA ™ plus prednisone was consistent with the known safety profile of each FDA-approved monotherapy. Of the patients in the MAGNITUDE study with a BRCA gene alteration, 41 percent who received AKEEGA ™ experienced a serious adverse event (AE). The most common AEs occurring in 20 percent or more of patients who received AKEEGA ™ plus prednisone versus patients who received placebo and AAP were musculoskeletal pain (44 percent vs. 42 percent, respectively), fatigue (43 percent vs. 30 percent), constipation (34 percent vs. 20 percent), hypertension (33 percent vs. 27 percent) and nausea (33 percent vs. 21 percent). Permanent discontinuation of any component of AKEEGA ™ due to an adverse reaction occurred in 15 percent of patients. "Janssen's legacy of advancing the science of prostate cancer has contributed to the evolution of transformational treatment approaches for more than a decade," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "This milestone, which marks the approval of Janssen's third prostate cancer treatment, highlights the importance of advancing precision medicine approaches and genetic testing for the treatment of patients with BRCA-positive mCRPC." About AKEEGA ™ AKEEGA ™ (niraparib and abiraterone acetate) is the first-and-only orally administered, once daily dual action tablet (DAT) of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, an androgen biosynthesis inhibitor. The novel DAT combination therapy targets two oncogenic drivers in patients with mCRPC and HRR gene alterations. AKEEGA ™ is indicated with prednisone for the treatment of adults with mCRPC and BRCA-positive mutations. The recommended starting dose is 200 mg niraparib/1,000 mg abiraterone acetate (two tablets). The 100 mg niraparib/1,000 mg abiraterone acetate dose option (two tablets) is available for dose reduction. In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GlaxoSmithKline [GSK] in 2019) for exclusive rights to niraparib in prostate cancer. About Metastatic Castration-Resistant Prostate Cancer Metastatic castration-resistant prostate cancer characterizes cancer that no longer responds to androgen deprivation therapy and has spread to other parts of the body. The most common metastatic sites are bones, followed by lungs and liver. Prostate cancer is the second most common cancer in men worldwide, behind lung cancer. More than one million patients around the world are diagnosed with prostate cancer each year. Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.2,3,4,5 About MAGNITUDE MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multi-center clinical study evaluating the safety and efficacy of the combination of AKEEGA ™ plus prednisone for patients with mCRPC, with or without certain HRR gene alterations, and who have not received prior therapy for mCRPC except for up to four months of AAP. The study included patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative), who were randomized 1:1 to receive niraparib 200 mg once daily plus AAP or placebo plus AAP.8 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations.9,10,11 The primary endpoint of the MAGNITUDE trial was rPFS assessed by blinded independent central review.12 Secondary endpoints included TCC, TSP and OS. Analysis of the group of patients with BRCA alterations was alpha controlled for rPFS and prespecified for other endpoints. Access to AKEEGA ™ (niraparib and abiraterone acetate) Once a patient and their doctor have decided that AKEEGA™ is right for the patient, Janssen can help find the resources patients may need to get started and stay on therapy. Janssen offers support navigating the payer processes to assist patients in gaining access to AKEEGA™. We can provide information on insurance coverage and potential out-of-pocket costs and identify options that may help make AKEEGA™ more affordable. If patients have commercial or private health insurance and need help paying for AKEEGA™, the Janssen CarePath Savings Program may be able to help. To learn more about access and affordability support visit JanssenCarePath.com or call 1-877-CarePath (1-877-227-3728). We also offer personalized support for patients that provides one-on-one guidance, information, and educational resources, which includes helping them explore cost support options. Patients can get connected to dedicated support from our Care Navigators by calling Janssen Compass® directly at 844-628-1234 or by visiting JanssenCompass.com and requesting an introductory call. Janssen Compass® is limited to education for patients about their Janssen therapy, its administration, and/or their disease. It is intended to supplement a patient's understanding of their therapy and is not intended to provide medical advice, replace a treatment plan from the patient's doctor or nurse, provide case management services, or serve as a reason to prescribe a Janssen medication. IMPORTANT SAFETY INFORMATION FOR AKEEGA ™ WARNINGS AND PRECAUTIONS The safety population described in the WARNINGS and PRECAUTIONS reflect exposure to AKEEGA™ in combination with prednisone in BRCAm patients in Cohort 1 (N=113) of MAGNITUDE. Myelodysplastic Syndrome/Acute Myeloid Leukemia AKEEGA™ may cause myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). MDS/AML, including cases with fatal outcome, has been observed in patients treated with niraparib, a component of AKEEGA™. All patients treated with niraparib who developed secondary MDS/cancer-therapy-related AML had received previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue AKEEGA™ if MDS/AML is confirmed. Myelosuppression AKEEGA™ may cause myelosuppression (anemia, thrombocytopenia, or neutropenia). In MAGNITUDE Cohort 1, Grade 3-4 anemia, thrombocytopenia, and neutropenia were reported, respectively in 28%, 8%, and 7% of patients receiving AKEEGA™. Overall, 27% of patients required a red blood cell transfusion, including 11% who required multiple transfusions. Discontinuation due to anemia occurred in 3% of patients. Monitor complete blood counts weekly during the first month of AKEEGA™ treatment, every two weeks for the next two months, monthly for the remainder of the first year and then every other month, and as clinically indicated. Do not start AKEEGA™ until patients have adequately recovered from hematologic toxicity caused by previous therapy. If hematologic toxicities do not resolve within 28 days following interruption, discontinue AKEEGA™ and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions AKEEGA™ may cause hypokalemia and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1)]. In post-marketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate, a component of AKEEGA™. Hypertension and hypertensive crisis have also been reported in patients treated with niraparib, a component of AKEEGA™. In MAGNITUDE Cohort 1, which used prednisone 10 mg daily in combination with AKEEGA™, Grades 3-4 hypokalemia was detected in 2.7% of patients on the AKEEGA™ arm and Grades 3-4 hypertension were observed in 14% of patients on the AKEEGA™ arm. The safety of AKEEGA™ in patients with New York Heart Association (NYHA) Class II to IV heart failure has not been established because these patients were excluded from MAGNITUDE. Monitor patients for hypertension, hypokalemia, and fluid retention at least weekly for the first two months, then once a month. Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia, or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. Control hypertension and correct hypokalemia before and during treatment with AKEEGA™. Discontinue AKEEGA™ in patients who develop hypertensive crisis or other severe cardiovascular adverse reactions. Hepatotoxicity AKEEGA™ may cause hepatotoxicity. Hepatotoxicity in patients receiving abiraterone acetate, a component of AKEEGA™, has been reported in clinical trials. In post-marketing experience, there have been abiraterone acetate-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure, and deaths. In MAGNITUDE Cohort 1, Grade 3-4 ALT or AST increases (at least 5 x ULN) were reported in 1.8% of patients. The safety of AKEEGA™ in patients with moderate or severe hepatic impairment has not been established as these patients were excluded from MAGNITUDE. Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with AKEEGA™, every two weeks for the first three months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient's baseline should prompt more frequent monitoring and may require dosage modifications. Permanently discontinue AKEEGA™ for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation, or in patients who develop ALT or AST ≥20 x ULN at any time after receiving AKEEGA™. Adrenocortical Insufficiency AKEEGA™ may cause adrenal insufficiency. Adrenocortical insufficiency has been reported in clinical trials in patients receiving abiraterone acetate, a component of AKEEGA™, in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased doses of corticosteroids may be indicated before, during, and after stressful situations. Hypoglycemia AKEEGA™ may cause hypoglycemia in patients being treated with other medications for diabetes. Severe hypoglycemia has been reported when abiraterone acetate, a component of AKEEGA™, was administered to patients receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide. Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with AKEEGA™. Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia. Increased Fractures and Mortality in Combination with Radium 223 Dichloride AKEEGA™ with prednisone is not recommended for use in combination with Ra-223 dichloride outside of clinical trials. The clinical efficacy and safety of concurrent initiation of abiraterone acetate plus prednisone/prednisolone and radium Ra 223 dichloride was assessed in a randomized, placebo-controlled multicenter study (ERA-223 trial) in 806 patients with asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases. The study was unblinded early based on an Independent Data Monitoring Committee recommendation. At the primary analysis, increased incidences of fractures (29% vs 11%) and deaths (39% vs 36%) have been observed in patients who received abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate plus prednisone. It is recommended that subsequent treatment with Ra-223 not be initiated for at least five days after the last administration of AKEEGA™, in combination with prednisone. Posterior Reversible Encephalopathy Syndrome AKEEGA™ may cause Posterior Reversible Encephalopathy Syndrome (PRES). PRES has been observed in patients treated with niraparib as a single agent at higher than the recommended dose of niraparib included in AKEEGA™. Monitor all patients treated with AKEEGA™ for signs and symptoms of PRES. If PRES is suspected, promptly discontinue AKEEGA™ and administer appropriate treatment. The safety of reinitiating AKEEGA™ in patients previously experiencing PRES is not known. Embryo-Fetal Toxicity The safety and efficacy of AKEEGA™ have not been established in females. Based on animal reproductive studies and mechanism of action, AKEEGA™ can cause fetal harm and loss of pregnancy when administered to a pregnant female. Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow). In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of AKEEGA™. Females who are or may become pregnant should handle AKEEGA™ with protection, e.g., gloves. Based on animal studies, AKEEGA™ may impair fertility in males of reproductive potential. ADVERSE REACTIONS The safety of AKEEGA™ in patients with BRCAm mCRPC was evaluated in Cohort 1 of MAGNITUDE. The most common adverse reactions (≥10%), including laboratory abnormalities, are decreased hemoglobin, decreased lymphocytes, decreased white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, increased AST, increased ALT, edema, dyspnea, decreased appetite, vomiting, dizziness, COVID-19, headache, abdominal pain, hemorrhage, urinary tract infection, cough, insomnia, increased bilirubin, weight decreased, arrhythmia, fall, and pyrexia. Serious adverse reactions reported in >2% of patients included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%). Fatal adverse reactions occurred in 9% of patients who received AKEEGA™, including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%). DRUG INTERACTIONS Effect of Other Drugs on AKEEGA™ Avoid coadministration with strong CYP3A4 inducers. Abiraterone is a substrate of CYP3A4. Strong CYP3A4 inducers may decrease abiraterone concentrations, which may reduce the effectiveness of abiraterone. Effects of AKEEGA™ on Other Drugs Avoid coadministration unless otherwise recommended in the Prescribing Information for CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug. Abiraterone is a CYP2D6 moderate inhibitor. AKEEGA™ increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates. Monitor patients for signs of toxicity related to a CYP2C8 substrate for which a minimal change in plasma concentration may lead to serious or life-threatening adverse reactions. Abiraterone is a CYP2C8 inhibitor. AKEEGA™ increases the concentration of CYP2C8 substrates, which may increase the risk of adverse reactions related to these substrates. Please see the full Prescribing Information for AKEEGA ™. *Dr. Chi has been a paid consultant to Janssen; Dr. Chi has not been paid for any media work. **Ms. Moneer has not been paid for any media work. About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension. Learn more at . Follow us at @JanssenGlobal and @JanssenUS. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of AKEEGA ™. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC; Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 AKEEGA Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 2 American Cancer Society. Cancer Facts & Figures 2023. Accessed May 11, 2023. 3 Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021 Aug 3;12(16):1600-1614. doi: 10.18632/oncotarget.28015. PMID: 34381565; PMCID: PMC8351605. Available at: 4 Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: A prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. doi:10.1200/JCO.18.00358. 5 Cavanagh, H., & Rogers, K. M. (2015). The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice, 13(1), 16. 6 Messina, C., Cattrini, C., Soldato, D., et al (2020). BRCA mutations in prostate cancer: Prognostic and predictive Implications. J Oncol., 2020, 4986365. 7 Na, R., Zheng, S. L., Han, M., et al (2017). Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. European Urology, 71(5), 740–747. 8 Chi et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Oral presentation, 2022 ASCO GU Annual Meeting. 9 AKEEGA ™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 10 Efstathiou E, et al. Niraparib With Abiraterone Acetate and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer and Homologous Recombination Repair Gene Alterations: Second Interim Analysis of MAGNITUDE. Poster presentation, 2023 ASCO GU Annual Meeting. February 16, 2023. 11 AKEEGA ™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 12 AKEEGA ™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. Media Contacts: Ania DiAntonio +1 215-620-9717 Suzanne Frost +1 416-317-0304 Investor Relations: Raychel Kruper [email protected] U.S. Medical Inquiries: +1 800-526-7736 SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson