b'FDA approval of LYNPARZA + abi/pred was based on an exploratory BRCAm subgroupLYNPARZA + abi/pred demonstrated improvement in rPFS vs placebo + abi/pred in patients with BRCAm mCRPC 1,6rPFS BY INVESTIGATOR100LYNPARZA: the FIRST PARPiASSESSMENT IN90 76 % RISK REDUCTION OF DISEASEEXPLORATORY BRCAmPROGRESSION OR DEATHapproved in combination withSUBGROUP 80abiraterone plus prednisone orHR=0.24 \x1f95% CI: 0.12\x1e0.45\x1dprednisolone (abi/pred) as initial70 LYNPARZA + abi/predProbability of rPFS (%)1-5 the approach to initial therapy for patients with60 Median rPFS (n=47)therapy for BRCAm mCRPC NRBRCAm mCRPC 50 (95% CI: NRNR)Not an actual patient. Median rPFS~8 mo40 (95% CI: 615)INDICATIONLYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated in combination with abiraterone and prednisone or prednisolone (abi/pred) for30the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).20Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. placebo + abi/pred 10 (n=38)PROpel: A phase 3 trial 0 Year 1 Year 20 2 4 6 8 10 12 14 16 18 20 22 24 26 28PROpel examined the efficacy of LYNPARZA + abi/pred vs abi/pred + placebo (active comparator) upon mCRPC diagnosis 1,6 Months since randomization PROpel was a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial Number of patients at riskITT population (N=796): mCRPC with or without HRR mutations LYNPARZA + abi/pred 47 44 43 40 40 38 36 33 32 27 16 14 7 5 0placebo + abi/pred38 33 29 22 20 16 13 11 10 7 6 6 2 0 0 FDA approval of LYNPARZA + abi/pred was based on an exploratory BRCAm subgroup (n=85)Patients were randomized 1:1 to receive either LYNPARZA (300 mg BID) + abiraterone (1000 mg QD) with prednisone or prednisolone (5 mg BID) (n=399)BRCAm subgroup (n=85)or placebo + abiraterone (1000 mg QD) with prednisone or prednisolone (5 mg BID) (n=397). LYNPARZA was continued until objective radiological diseaserPFS events, n (%): 14/47 (30) with LYNPARZA + abi/pred and 28/38 (74) with placebo + abi/predprogression determined by investigator or unacceptable toxicity. All patients received a GnRH analog or had prior bilateral orchiectomyResults from the BICR assessment were consistent with the investigator-assessed rPFS resultsPatients were stratified by metastatic site and whether they received prior docetaxel at mHSPC stage. BRCAm status was not a stratification factor. OS analysis: 70% reduction in risk of death (HR=0.30 [95% CI: 0.150.59]) for LYNPARZA + abi/pred vs placebo + abi/pred. OS events, n (%): 13/47 (28) Prior abiraterone was not allowed and 25/38 (66), respectively Primary endpoint (ITT): rPFS by investigator assessment*Additional efficacy outcome measure (ITT): Overall survival BRCAm status was not a stratification factor in PROpel, and analysis was not controlled for Type 1 error Safety and tolerability ITT population (n=796) Exploratory BRCAm subgroup analyses Statistically significant improvement in rPFS* was observed for LYNPARZA + abi/pred compared with placebo + abi/pred. OS for LYNPARZA + abi/pred compared to placebo + abi/pred did not reach statistical significance in the ITT population Investigator-assessed rPFS* and OS in patients with BRCAm mCRPC (n=85) Patients without an identified BRCA mutation (n=711) Sensitivity analysis of rPFS by BICR Results from an exploratory analyses in this subgroup (rPFS: HR=0.77 [95% CI: 0.630.96] and OS: HR=0.92 [95% CI: 0.741.14]) indicated that the BRCAm status was assessed after randomization and before primary analysis by both NGS-based tumor tissue and ctDNA tests. BRCAm classification criteria in improvement in the ITT population was primarily attributed to the results seen in the BRCAline with the FDA-approved assays were used to determine the deleterious and suspected deleterious somatic or germline mutation status of patients. m subgroup*Radiological progression-free survival (rPFS) assessed by investigator per RECIST v1.1 (soft tissue) and PCWG3 (bone) criteria. IMPORTANT SAFETY INFORMATION (Contd)IMPORTANT SAFETY INFORMATION data of two randomized, placebo-controlled clinical studies (PROfoundDRUG INTERACTIONS Choose LYNPARZA + abi/pred as initial therapy for BRCAm mCRPCCONTRAINDICATIONS and PROpel) in patients with metastatic castration-resistant prostate Anticancer Agents: Clinical studies of LYNPARZA with otherto help give your patients more time without disease progression There are no contraindications for LYNPARZA. cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, myelosuppressive anticancer agents, including DNA-damaging agents, including pulmonary embolism in 6%. In the control arms, VTE occurred in indicate a potentiation and prolongation of myelosuppressive toxicity. References: 1. LYNPARZA (olaparib) [prescribing information]. Wilmington, DE: WARNINGS AND PRECAUTIONS 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signsCYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3AAstraZeneca Pharmaceuticals LP; 2023. 2. Akeega (niraparib and abiraterone acetate) Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):and symptoms of venous thrombosis and pulmonary embolism, and treatinhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor[prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2023. 3. Rubraca Occurred in approximately 1.2% of patients with various BRCAm, as medically appropriate, which may include long-term anticoagulation as must be coadministered, reduce the dose of LYNPARZA. Advise patients to(rucaparib) [prescribing information]. Vienna, Austria: zr pharma& GmbH; 2023.gBRCAm, HRR gene-mutated or HRD-positive cancers who receivedclinically indicated.avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice4. Talzenna (talazoparib) [prescribing information]. New York, NY: Pfizer Inc.; 2024.LYNPARZA as a single agent or as part of a combination regimen,Embryo-Fetal Toxicity: Based on its mechanism of action and findings in during LYNPARZA treatment. 5. Zejula (niraparib) [prescribing information]. Durham, NC: GlaxoSmithKline; 2024.consistent with the approved indications, and the majority of events hadanimals, LYNPARZA can cause fetal harm. Verify pregnancy status in femalesCYP3A Inducers: Avoid coadministration of strong or moderate CYP3A6. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for a fatal outcome. The median duration of therapy in patients whoof reproductive potential prior to initiating treatment. inducers when using LYNPARZA. metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9). Published online developed MDS/AML was approximately 2 years (range: 6 months to 4Females USE IN SPECIFIC POPULATIONS June 3, 2022. doi:10.1056/EVIDoa2200043years). All of these patients had previous chemotherapy with platinumAdvise females of reproductive potential of the potential risk to a fetusLactation: No data are available regarding the presence of olaparib inabi/pred=abiraterone plus prednisone or prednisolone; BICR=blinded independentagents and/or other DNA-damaging agents, including radiotherapy. and to use effective contraception during treatment and for 6 months human milk, its effects on the breastfed infant or on milk production.central review; BID=twice daily; BRCAm=BRCA-mutated; CI=confidence interval; Do not start LYNPARZA until patients have recovered from hematologicalfollowing the last dose. Because of the potential for serious adverse reactions in the breastfed ctDNA=circulating tumor DNA; gBRCAm=germline BRCAmutated; GnRH=gonadotropin-toxicity caused by previous chemotherapy (Grade 1). Monitor completeMales infant, advise a lactating woman not to breastfeed during treatment withreleasing hormone; HR=hazard ratio; HRD=homologous recombination deficiency; blood count for cytopenia at baseline and monthly thereafter for clinicallyLYNPARZA and for 1 month after receiving the final dose. HRR=homologous recombination repair; ITT=intent-to-treat; mCRPC=metastaticsignificant changes during treatment. For prolonged hematologicalAdvise male patients with female partners of reproductive potential orcastration-resistant prostate cancer; mHSPC=metastatic hormone-sensitive prostatetoxicities, interrupt LYNPARZA and monitor blood count weekly who are pregnant to use effective contraception during treatment and forPediatric Use: The safety and efficacy of LYNPARZA have not beencancer; mo=months; NGS=next-generation sequencing; NR=not reached; OS=overall until recovery. 3 months following the last dose of LYNPARZA and to not donate sperm established in pediatric patients. survival; PARPi=poly (ADP-ribose) polymerase inhibitor; PCWG3=Prostate Cancer Working during this time. Hepatic Impairment: No adjustment to the starting dose is requiredGroup 3; QD=once daily; RECIST=Response Evaluation Criteria in Solid Tumors; If the levels have not recovered to Grade 1 or less after 4 weeks, refer theADVERSE REACTIONSMetastatic Castration-Resistant Prostatein patients with mild or moderate hepatic impairment (Child-PughrPFS=radiological progression-free survival.patient to a hematologist for further investigations, including bone marrowCancer in Combination with Abiraterone and Prednisone orclassification A and B). There are no data in patients with severe hepatic analysis and blood sample for cytogenetics. Discontinue LYNPARZA if Prednisolone impairment (Child-Pugh classification C).MDS/AML is confirmed. Most common adverse reactions (Grades 1-4) in 10% of patients who Renal Impairment: No dosage modification is recommended in patients Visit LYNPARZAprhcp.com to explore Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZAreceived LYNPARZA/abiraterone with a difference of 5% compared to with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault).additional data from the PROpel trialmonotherapy, and some cases were fatal. If patients present with new orplacebo for PROpel were: anemia (48%), fatigue (including asthenia) In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the worsening respiratory symptoms such as dyspnea, cough, and fever, or a(38%), nausea (30%), diarrhea (19%), decreased appetite (16%), dose of LYNPARZA to 200 mg twice daily. There are no data in patients with radiological abnormality occurs, interrupt LYNPARZA treatment and initiatelymphopenia (14%), dizziness (14%), and abdominal pain (13%). severe renal impairment or end-stage renal disease (CLcr 30 mL/min).prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmedMost common laboratory abnormalities (Grades 1-4) in 20% of patients Please see accompanying Brief Summary of Prescribing Information and treat patient appropriately. who received LYNPARZA/abiraterone for PROpel were: decrease in on the following pages. LYNPARZA is a registered trademarkVenous Thromboembolism (VTE): Including severe or fatal pulmonaryof the AstraZeneca group of companies.embolism (PE) occurred in patients treated with LYNPARZA. In the combinedhemoglobin (97%), decrease in lymphocytes (70%), decrease in plateletsYou are encouraged to report negative side effects of prescription drugs to 2024 AstraZeneca. All rights reserved. (23%), and decrease in absolute neutrophil count (23%). the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. US-895025/24'