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Zepzelca® IMforte Data Webcast Innovating to Transform the Lives of Patients and Their Families June 10, 2025
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June 10, 2025 Transforming Lives. Redefining Possibilities. Caution Concerning Forward-Looking Statements This presentation contains forward-looking statements and financial targets, including, but not limited to, statements related to: the Company’s development, regulatory and commercialization strategy; the advancement of pipeline programs and the timing of development activities, regulatory activities and submission s related thereto; the Company’s expectations with respect to its products and product candidates and the potential of the Company’s products and product candidates, including the potential o f zanidatamab to be more than a two billion dollar peak potential and to become the therapy of choice for multiple HER2+ tumors, the near-term commercialization potential of dordaviprone and the potential of Zepzelca plus atezolizumab to become the treatment of choice in 1L ES-SCLC in the maintenance setting; the Company’s ability to realize the commercial potential of its products including the commercial plans with respect to Zepzelca in 1L ES-SCLC, if approved; potential regulatory approvals; and other statements that are not historical facts. These forward-looking statements are based on the Company’s current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the successful completion of development and regulatory activities with respect to t he Company’s product candidates including Zepzelca in 1L-ESLC, zanidatamab in multiple HER2+ tumors and dordaviprone in recurrent H3 K27M-mutant diffuse glioma; obtaining and maintaining adequate coverage and reimbursement for the Company’s products; the time-consuming and uncertain regulatory approval process, including the risk that the Company’s current and/or pla nned regulatory submissions may not be submitted, accepted or approved by applicable regulatory authorities in a timely manner or at all, including the risk that the Company's supplementa l new drug application for Zepzelca's use in combination with atezolizumab as maintenance therapy in 1L ES-SCLC for patients who have not progressed after induction chemotherapy and/or the C ompany's new drug application for dordaviprone for treatment of H3 K27M-mutant diffuse glioma in adult and pediatric patients with progressive disease following prior therapy may not be app roved in a timely manner or at all, the costly and time-consuming pharmaceutical product development and the uncertainty of clinical success, including risks related to failure or delays in s uccessfully initiating or completing clinical trials and assessing patients; global economic, financial, and healthcare system disruptions and the current and potential future negative impacts to the Co mpany’s business operations and financial results; protecting and enhancing the Company’s intellectual property rights and the Company’s commercial success being dependent upon the Company ob taining, maintaining and defending intellectual property protection and exclusivity for its products and product candidates; delays or problems in the supply or manufacture of the Co mpany’s products and product candidates; complying with applicable U.S. and non-U.S. regulatory requirements, including those governing the research, development, manufacturing and distribution; government investigations, legal proceedings and other actions; the sufficiency of the Company’s cash flows and capital resources; and other risks and uncertainties affecting the Company, including those described from time to time under the caption “Risk Factors” and elsewhere in Jazz Pharmaceuticals’ Securities and Exchange Commission filings and reports, including the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 as supplemented by the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, and future filings and reports by the Company. Other risks and uncertainties of which the Company is not currently aware may also affect the Company’s forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. 2
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June 10, 2025 Agenda Introduction and Overview Renée Galá President and Chief Operating Officer Clinical Perspectives on Small-Cell Lung Cancer and Results from the IMforte Trial Stephen Liu, M.D. Medical Oncologist, Associate Professor of Medicine, Director of Thoracic Oncology at Georgetown University, Head of Developmental Therapeutics at Georgetown Lombardi Comprehensive Cancer Center Zepzelca: Clinical and Development Overview Rob Iannone, M.D., M.S.C.E. Executive Vice President, Global Head of Research and Development and Chief Medical Officer Zepzelca: Commercial Overview Sam Pearce Executive Vice President, Chief Commercial Officer 3 Intended for U.S investor audiences only.
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Introduction and Overview Renée Galá President and Chief Operating Officer June 10, 2025
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June 10, 2025 Highly Differentiated Medicines for Patients with Serious Diseases 1L / 2L = first- and second-line; ALL/LBL = acute lymphoblastic leukemia / lymphoblastic lymphoma; ES -SCLC = extensive-stage small cell lung cancer; HER2+ = human epidermal growth factor receptor 2 +; HSR = hypersensitivity; IH = idiopathic hypersomnia. 1Based on 1Q25 Xywav and Epidiolex net product sales, respectively. Diverse product mix + strong cash flow generation NeuroscienceOncology #1 branded treatment for narcolepsy and only approved IH therapy1 #1 branded treatment for epilepsy1 Standard of care in pediatric ALL/LBL patients with asparaginase HSR reaction Leading treatment in 2L ES-SCLC; expansion opportunity in 1L ES-SCLC Potential to be the therapy of choice in multiple HER2+ tumors Top-line growth driven by diversified portfolio of highly differentiated medicines 5
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June 10, 20256 Evolution of Oncology Portfolio 2014 2019 2022 Expanded commercial portfolio in rare / orphan diseases Defitelio Gentium Acquisition Zepzelca Licensing Agreement Rapidly accretive; set stage for future oncology growth in solid tumors, including zanidatamab Zanidatamab Licensing Agreement $2B+ peak potential, multiple indications1 2012 Erwinaze EUSA Acquisition Expanded oncology footprint, set the stage for Rylaze 2016 Strengthened hem/onc franchise Vyxeos Celator Acquisition Note: Timeline shows select corporate development activity since 2012. Hem/ onc = hematology & oncology. 1Pending regulatory approval. Oncology transactions driving commercial growth and expanding R&D capabilities Chimerix Acquisition Expanded commercial portfolio with near-term commercial potential1 2025 Denotes data presented in oral presentations at ASCO 2025 Rylaze Approval Internally Developed Leveraged internal R&D capabilities to deliver new therapy to market 2022
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IMforte Trial Results Stephen Liu, M.D. Medical Oncologist, Associate Professor of Medicine, Director of Thoracic Oncology at Georgetown University, Head of Developmental Therapeutics at Georgetown Lombardi Comprehensive Cancer Center June 10, 2025
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Shubham Pant, M.D., MBBS Dept. of Gastrointestinal Medical Oncology & Dept. of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer CenterDr. Stephen V. Liu, MD, is the Director of Thoracic Oncology and Head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Liu is a board-certified medical oncologist. He leads the drug development program at Georgetown University and oversees thoracic oncology research at the cancer center. In addition to leading national and global clinical trials for the treatment of lung cancer, Dr. Liu is also the co-host for the official International Association for the Study of Lung Cancer, or IASLC, podcast, “Lung Cancer Considered.” June 10, 20258
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June 10, 20259 9 Lurbinectedin + atezolizumab as first-line maintenance treatment in patients with extensive-stage small cell lung cancer: Primary results of the Phase 3 IMforte trial Luis Paz-Ares,1 Hossein Borghaei,2 Stephen V. Liu,3 Solange Peters,4 Roy S. Herbst,5 Katarzyna Stencel,6 Margarita Majem,7 Grzegorz Czyżewicz,8 Reyes Bernabé Caro,9 Ki Hyeong Lee,10 Melissa L. Johnson,11 Nuri Karadurmuş,12 Christian Grohé,13 Vaikunth Cuchelkar,14 Vilma Graupner,15 Monika Kaul,14 Ya-Chen Lin,14 Debasis Chakrabarti,16 Kamalnayan Bhatt,16 Martin Reck17 1Hospital Universitario 12 de Octubre, H12O -CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain; 2Fox Chase Cancer Center, Philadelphia, PA, USA; 3Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; 4University Hospital CHUV, Lausanne, Switzerland; 5Yale School of Medicine, New Haven, CT, USA; 6Wielkopolska Center of Pulmonology and Thoracic Surgery of Eugenia and Janusz Zeyland, Poznan, Poland; 7Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 8The John Paul II Specialist Hospital, Kraków, Poland; 9Hospital Universitario Virgen del Rocío, Seville, Spain; 10Chungbuk National University Hospital, Cheongju, South Korea; 11Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN, USA; 12University of Health Sciences, Gülhane Training and Research Hospital, Ankara, Türkiye; 13Klinik für Pneumologie, Evangelische Lungenklinik Berlin, Berlin, Germany; 14Genentech Inc, South San Francisco, CA, USA; 15F. Hoffmann-La Roche Ltd, Basel, Switzerland; 16Jazz Pharmaceuticals plc, Dublin, Ireland; 17Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany
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June 10, 20251010 Key takeaway points The combination of lurbinectedin + atezolizumab has the potential to become the new standard of care for 1L maintenance treatment of ES-SCLC IMforte demonstrated a statistically significant and clinically meaningful improvement in PFS and OS with 1L maintenance treatment with lurbinectedin + atezolizumab vs atezolizumab in patients with ES-SCLC The safety profile of the combination was predictable with an increased incidence of AEs, most of which were low grade; treatment discontinuation rates were low
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June 10, 20251111 Background • Despite improved efficacy with 1L immune checkpoint inhibitors (ICIs) + platinum-based chemotherapy, most patients with ES-SCLC eventually experience disease progression and long-term survival remains limited1-5 • Due to the high attrition rate in ES-SCLC of ~60%6, offering the most effective treatment in the front-line setting before progression is crucial to improve outcomes in this difficult-to-treat disease • Lurbinectedin is an alkylating agent and transcription inhibitor that is approved in the US and other countries for the treatment of patients with metastatic SCLC who experienced disease progression on or after platinum-based chemotherapy • In pre-clinical studies, lurbinectedin was shown to synergize with ICIs7,8 to achieve high rates of tumor regression and induce long-term T-cell memory9,10 • In Phase 1/2 trials in patients with relapsed ES-SCLC, the combination of lurbinectedin and ICIs was well tolerated with promising activity11-13 1L, first line; ES-SCLC, extensive-stage small cell lung cancer; OS, overall survival; PFS, progression-free survival; SCLC, small cell lung cancer. 1. Liu SV, et al. J Clin Oncol 2021;39:619-30. 2. Paz-Ares L, et al. ESMO Open 2022;7:100408. 3. Goldman JW, et al. Lancet Oncol 2021;22:51-65. 4. Reck M, et al. Lung Cancer 2024;196:107924. 5. Cheng Y , et al. JAMA 2022;328:1223-32. 6. Ramirez RA, et al. ASCO 2022 [abstract 8584]. 7. Xie W, et al. Oncoimmunology 2019;8:e1656502. 8. Chakraborty S, et al. Cell Rep Med 2024;5:101852. 9. Russo-Cabrera JS, et al. Ann Oncol 2023;34:S636. 10. Russo-Cabrera JS, et al. AACR 2025 [abstract 5837]. 11. Calles A, et al. J Thorac Oncol 2025 doi: 10.1016/j.jtho.2025.02.005. 12. Ponce Aix S, et al. J Immunother Cancer 2021;9(Suppl 2):A493. 13. Ponce Aix S, et al. ASCO 2025 [abstract 8013]. The global, open-label, randomized, Phase 3 IMforte study investigated the efficacy and safety of lurbinectedin + atezolizumab versus atezolizumab for the maintenance treatment of ES-SCLC in patients whose disease had not progressed after 1L induction treatment with atezolizumab + carboplatin + etoposide
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June 10, 20251212 IMforte study design ClinicalTrials.gov ID: NCT05091567. a Administered per standard dose. b 73% of patients continued from induction to maintenance. c With prophylactic granulocyte colony-stimulating factor and anti-emetics. atezo, atezolizumab; BL, baseline; carbo, carboplatin; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group performance status; ENR, enrollment; etop, etoposide; INV-PFS, investigator-assessed PFS; IRF-PFS, independent review facility-assessed PFS; IV, intravenously; LDH, lactate dehydrogenase; lurbi, lurbinectedin; MC1D1, maintenance Cycle 1 Day 1; PCI, prophylactic cranial irradiation; q3w, every 3 weeks; R, randomization; ULN, upper limit of normal; Y/N, yes/no. Stratification factors for randomization • ECOG PS (0/1) • LDH (≤ULN/>ULN) • Presence of liver metastases (Y/N) at induction BL • Prior receipt of PCI (Y/N) R 1:1 Induction phase Maintenance phase Treat until PD or unacceptable toxicity No crossover allowedAtezo (1200 mg) IV q3w Lurbi (3.2 mg/m2) + atezo (1200 mg) IV q3wc Eligibility criteria • No prior systemic treatment for ES-SCLC • No CNS metastases • ECOG PS 0/1 N=660 Atezo + carbo + etop (4 cycles q3w)a Eligibility criteria • Ongoing CR/PR or SD following induction therapy • ECOG PS 0/1 N=483b Second screeningFirst screening Follow-up Efficacy endpoint assessments started from randomization into the maintenance phase; safety analyses were from MC1D1 ENR Primary endpoints IRF-PFS and OS Secondary endpoints included INV-PFS, ORR, DOR, and safety Last patient randomized: April 30, 2024 Clinical cutoff: July 29, 2024
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June 10, 20251313 Statistical analysis plan • OS ‒ Target HR of 0.71 with a power of 85% ‒ Interim analysis occurred when ~219 deaths were observed in the FASa or when the minimum follow-upb was completed, whichever occurred later ‒ If OS results were statistically significant at the interim analysis, they would constitute the primary analysis • IRF-PFS ‒ No interim analysis ‒ Primary analysis was conducted at the time of OS interim analysis a The FAS was defined as all patients randomized into the maintenance phase regardless of whether or not the assigned study treatment was received. b The minimum follow-up was defined as 5 months after the target sample size of 450 participants had been randomized. FAS, full analysis set. Type 1 error rate control strategy Lurbi + atezo vs atezo 2-sided α=0.05 OS (α=0.049) IRF-PFS (α=0.001) If rejected, α=0.001 will be passed to OS If rejected, α=0.049 will be passed to IRF-PFS
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June 10, 20251414 Baseline characteristics of patients randomized into the maintenance phase Clinical cutoff: July 29, 2024. a Includes American Indian or Alaska Native and Black or African American patients, as well as patients with unreported race. b Stratification factors for randomization; data determined from electronic case-report forms. c n=236 in the lurbi + atezo arm and n=240 in the atezo arm; 7 randomized patients did not have a maintenance screening tumor assessment. d Randomization of these patients was in violation of the protocol. BL, baseline. PCI, prophylactic cranial irradiation. Characteristic Lurbi + atezo (n=242) Atezo (n=241) Age, median (range), years 65.0 (38-85) 67.0 (35-85) <65 years, n (%) 118 (48.8) 90 (37.3) Sex, male, n (%) 151 (62.4) 151 (62.7) Race, n (%) White 195 (80.6) 199 (82.6) Asian 31 (12.8) 31 (12.9) Othera 16 (6.6) 11 (4.6) Current or previous tobacco use history, n (%) 235 (97.1) 236 (97.9) Liver metastases at induction BL , n (%)b 100 (41.3) 94 (39.0) Prior PCI, n (%)b 34 (14.0) 37 (15.4) ECOG PS 0 at maintenance BL, n (%)b 105 (43.4) 102 (42.3) LDH ≤ULN at maintenance BL, n (%)b 176 (72.7) 179 (74.3) Time from induction Cycle 1 Day 1 to randomization, median (range), mo 3.2 (2.6-4.6) 3.2 (2.7-5.2) Response to induction therapy, n (%)c CR/PR 206 (87.3) 213 (88.8) SD 28 (11.9) 25 (10.4) PDd 2 (0.8) 2 (0.8)
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June 10, 20251515 No. at risk Atezo Lurbi + atezo 41.2% 18.7% IRF-PFS (%) Time from randomization (months) 6-mo IRF-PFS 12-mo IRF-PFS R PFS assessment started from randomization into the maintenance phase 20.5% 12.0% IRF-PFS from randomization into maintenance phase Clinical cutoff: July 29, 2024; median survival follow-up: 15.0 mo (minimum follow-up: 3.0 mo). CI, confidence interval; HR, hazard ratio. IRF-PFS Lurbi + atezo (n=242) Atezo (n=241) Events, n (%) 174 (71.9) 202 (83.8) PFS, median (95% CI), mo 5.4 (4.2, 5.8) 2.1 (1.6, 2.7) Stratified HR (95% CI) 0.54 (0.43, 0.67) Stratified P value (2-sided) <0.0001 α boundary (2-sided) 0.001 Investigator-assessed PFS was consistent with IRF -PFS • Median: 5.4 mo with lurbi + atezo and 2.7 mo with atezo (stratified HR, 0.55 [95% CI: 0.45, 0.68])
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June 10, 20251616 Baseline risk factors Events/patients, n/N Unstratified IRF-PFS HR (95% CI)Lurbi + atezo Atezo All patients 174/242 202/241 0.56 (0.46, 0.69) Age, years <65 86/118 73/90 0.64 (0.46, 0.87) ≥65 88/124 129/151 0.51 (0.38, 0.67) Sex Male 110/151 131/151 0.49 (0.38, 0.64) Female 64/91 71/90 0.69 (0.49, 0.98) Racea White 140/195 167/199 0.58 (0.46, 0.73) Asian 22/31 26/31 0.48 (0.27, 0.86) Tobacco use historya Current 61/88 57/73 0.65 (0.45, 0.95) Previous 107/147 141/163 0.53 (0.41, 0.68) Liver metastases at induction BLb Yes 75/100 87/94 0.45 (0.33, 0.62) No 99/142 115/147 0.62 (0.48, 0.82) Prior PCIb Yes 25/34 29/37 0.76 (0.44, 1.31) No 149/208 173/204 0.53 (0.42, 0.66) ECOG PSb 0 76/105 82/102 0.58 (0.42, 0.80) 1 98/137 120/139 0.56 (0.43, 0.73) LDHb ≤ULN 123/176 150/179 0.53 (0.41, 0.67) >ULN 51/66 52/62 0.65 (0.44, 0.96) Response to induction therapya,c CR/PR 143/206 176/213 0.53 (0.42, 0.67) SD 26/28 23/25 0.72 (0.40, 1.29) 0.1 1 4 IRF-PFS subgroup analysis Clinical cutoff: July 29, 2024; median survival follow-up: 15.0 mo (minimum follow-up: 3.0 mo). a Data from subgroups with small numbers are not displayed. b Stratification factor for randomization; data determined from electronic case-report forms. c n=236 in the lurbi + atezo arm and n=240 in the atezo arm; 7 randomized patients did not have a maintenance screening tumor assessment. Favors atezoFavors lurbi + atezo
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June 10, 20251717 44.1% 56.3% No. at risk Atezo Lurbi + atezo 12-mo OS OS (%) Time from randomization (months) R OS assessment started from randomization into the maintenance phase (median time from induction C1D1 to randomization: 3.2 months in each arm) OS from randomization into maintenance phase Clinical cutoff: July 29, 2024; median survival follow-up: 15.0 mo (minimum follow-up: 3.0 mo). a As determined by the Hwang-Shih-Decani alpha spending function with the gamma parameter of −1.5. OS Lurbi + atezo (n=242) Atezo (n=241) Events, n (%) 113 (46.7) 136 (56.4) OS, median (95% CI), mo 13.2 (11.9, 16.4) 10.6 (9.5, 12.2) Stratified HR (95% CI) 0.73 (0.57, 0.95) Stratified P value (2-sided) 0.0174 α boundary (2-sided)a 0.0313
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June 10, 20251818 a Median time from start of induction treatment to randomization was analyzed for 483 randomized patients. Note: 660 patients were enrolled into the induction phase, out of whom 177 patients were not randomized into the maintenance phase. Maintenance treatment Atezo Median OS from randomization: 10.6 months Maintenance treatment Lurbi + atezo Median OS from randomization: 13.2 monthsInduction treatment Atezo + carbo + etop 3.2 monthsa R IMforte results do not include time on induction treatment OS from randomization into maintenance phase OS (%) Time from randomization (months) OS Lurbi + atezo (n=242) Atezo (n=241) Events, n (%) 113 (46.7) 136 (56.4) OS, median (95% CI), mo 13.2 (11.9, 16.4) 10.6 (9.5, 12.2) Stratified HR (95% CI) 0.73 (0.57, 0.95) Stratified P value (2-sided) 0.0174 α boundary (2-sided)a 0.0313
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June 10, 20251919 Baseline risk factors Events/patients, n/N Unstratified OS HR (95% CI)Lurbi + atezo Atezo All patients 113/242 136/241 0.74 (0.58, 0.96) Age, years <65 53/118 49/90 0.77 (0.52, 1.14) ≥65 60/124 87/151 0.76 (0.55, 1.05) Sex Male 75/151 88/151 0.72 (0.53, 0.98) Female 38/91 48/90 0.78 (0.51, 1.19) Racea White 92/195 118/199 0.71 (0.54, 0.94) Asian 13/31 14/31 0.86 (0.40, 1.84) Tobacco use historya Current 38/88 39/73 0.79 (0.51, 1.24) Previous 72/147 94/163 0.76 (0.56, 1.03) Liver metastases at induction BLb Yes 55/100 63/94 0.70 (0.48, 1.00) No 58/142 73/147 0.76 (0.54, 1.07) Prior PCIb Yes 16/34 18/37 1.02 (0.52, 2.00) No 97/208 118/204 0.70 (0.53, 0.92) ECOG PSb 0 51/105 53/102 0.88 (0.60, 1.29) 1 62/137 83/139 0.66 (0.47, 0.92) LDHb ≤ULN 72/176 97/179 0.66 (0.49, 0.90) >ULN 41/66 39/62 0.96 (0.62, 1.50) Response to induction therapy a,c CR/PR 92/206 115/213 0.76 (0.57, 0.99) SD 17/28 18/25 0.62 (0.31, 1.24) 0.1 1 4 OS subgroup analysis Clinical cutoff: July 29, 2024; median survival follow-up: 15.0 mo (minimum follow-up: 3.0 mo). a Data from subgroups with small numbers are not displayed. b Stratification factor for randomization; data determined from electronic case-report forms. c n=236 in the lurbi + atezo arm and n=240 in the atezo arm; 7 randomized patients did not have a maintenance screening tumor assessment. Favors atezoFavors lurbi + atezo
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June 10, 20252020 Confirmed IRF-assessed ORR and DOR during the maintenance phase • Background: At the time of randomization, 88% of patients had CR/PR and 11% had SD to induction therapy ‒ Tumor response in the maintenance phase was assessed against maintenance baseline Clinical cutoff: July 29, 2024. a Measurable disease was not an inclusion criterion to enter the maintenance phase. b The confirmed ORR was defined as the proportion of randomized patients with a CR or PR on two consecutive occasions ≥4 weeks apart after randomization and was assessed in patients who had measurable disease at maintenance baseline. c DOR was assessed in patients who had a confirmed objective response in the maintenance phase. NE, not estimable. Patients with measurable diseasea Lurbi + atezo (n=175) Atezo (n=182) Confirmed objective response, n (%) (95% CI)b 34 (19.4) (13.9, 26.1) 19 (10.4) (6.4, 15.8) Difference in ORR (95% CI), % 9.0 (1.1, 16.9) CR, n (%) 4 (2.3) 1 (0.5) PR, n (%) 30 (17.1) 18 (9.9) SD, n (%) 96 (54.9) 68 (37.4) PD, n (%) 34 (19.4) 87 (47.8) Missing or non-evaluable, n (%) 11 (6.3) 8 (4.4) DORc Responders with an event/responders, n (%) 14/34 (41.2) 11/19 (57.9) Median DOR (95% CI), mo 9.0 (5.5, NE) 5.6 (4.2, NE)
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June 10, 20252121 Follow-up systemic anticancer treatments Clinical cutoff: July 29, 2024. Patients, n (%) Lurbi + atezo (n=242) Atezo (n=241) Patients who discontinued maintenance treatment 197 208 Patients with ≥1 follow-up systemic anticancer treatment 108 (44.6) 132 (54.8) Chemotherapy 89 (36.8) 119 (49.4) Immunotherapy 25 (10.3) 20 (8.3) Targeted therapy 3 (1.2) 2 (0.8) Other 3 (1.2) 3 (1.2) At the time of clinical cutoff, no patient in the lurbi + atezo arm and 22 patients (9.1%) in the atezo arm had received follow-up lurbi treatment
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June 10, 20252222 Safety summary during the maintenance phase Clinical cutoff: July 29, 2024. One patient randomized to the atezo arm did not receive treatment and was not included in the safety analysis set. a Sepsis and febrile neutropenia, both considered related to lurbi. b Sepsis considered related to atezo. c Atezo dose modifications were not permitted. d AESI for lurbi and atezo were pre-specified based on their mechanism of action and were independent of the causal relationship assigned by the investigator. AE, adverse event; AESI, adverse events of special interest. Patients with ≥1 AE, n (%) Lurbi + atezo (n=242) Atezo (n=240) All-cause AEs 235 (97.1) 194 (80.8) Grade 3/4 AEs 92 (38.0) 53 (22.1) Treatment-related Grade 3/4 AEs 62 (25.6) 14.0 (5.8) Grade 5 AEs 12 (5.0) 6 (2.5) Treatment-related Grade 5 AEs 2 (0.8)a 1 (0.4)b Serious AEs 75 (31.0) 41 (17.1) AEs leading to discontinuation of any study drug 15 (6.2) 8 (3.3) AEs leading to dose interruption/ modification of any study drug c 92 (38.0) 33 (13.8) Patients with ≥1 AE, n (%) Lurbi + atezo (n=242) Atezo (n=240) Lurbinectedin AESId 93 (38.4) 62 (25.8) Grade 5 AESI 7 (2.9) 4 (1.7) Atezolizumab AESId 76 (31.4) 54 (22.5) Grade 5 AESI 0 0 Atezolizumab AESI requiring corticosteroids 40 (16.5) 18 (7.5) Median treatment duration, mo 4.1 (lurbi)/ 4.2 (atezo) 2.1 Median number of doses received 6.5 (lurbi)/ 7.0 (atezo) 4.0
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June 10, 20252323 All-cause AEs with incidence ≥10% in either arm Clinical cutoff: July 29, 2024. Percentage labels represent all-grade AEs, including Grade 5 AEs. Grade 5 AEs occurred in 12 (5.0%) patients in the lurbi + atezo arm and 6 (2.5%) patients in the atezo arm. a Includes 1 Grade 5 AE. b Grade 5 infections: lurbi + atezo arm (n=6 [2.5%]): COVID-19 pneumonia, pneumonia, pneumonia viral, sepsis, septic shock, and vascular device infection (n=1 each); atezo arm (n=4 [1.7%]): pneumonia (n=2), abscess intestinal, and sepsis (n=1 each). -100% -80% -60% -40% -20% 0% 20% 40% 60% 80% 100% Asthenia Anemia Any AE Nausea Fatigue Decreased appetite Platelet count decreased Diarrhea Vomiting Neutrophil count decreased Thrombocytopenia Constipation Neutropenia Lurbi + atezo Atezo Grade 1/2 Grade 3/4 Patients (%) 97.1% 36.4% 31.8% 20.2% 16.9% 15.3% 14.0% 13.6% 12.8% 12.8% 12.8% 12.0% 10.7% 80.8% 4.2% 6.7% 7.9% 6.7% 2.9% 7.5% 2.5% 6.3% 1.7% 1.3% 6.3% 1.7% Febrile neutropenia Lurbi + atezo: 1.7%a Atezo: 0% Grade 3/4 infections and infestationsb Lurbi + atezo: 6.6% Atezo: 5.0%
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June 10, 20252424 Conclusions • IMforte demonstrated a statistically significant and clinically meaningful improvement in IRF -PFS and OS with 1L maintenance treatment with lurbinectedin + atezolizumab vs atezolizumab in patients with ES -SCLC ‒ Stratified IRF-PFS HR: 0.54 (95% CI: 0.43, 0.67); P<0.0001 ‒ Stratified OS HR: 0.73 (95% CI: 0.57, 0.95); P=0.0174 • IRF-PFS and OS benefit with lurbinectedin + atezolizumab was generally consistent across the majority of subgroups • Despite the higher rate of Grade 3/4 AEs and SAEs, there were no new or unexpected safety signals with lurbinectedin + atezolizumab ‒ The safety profile was predictable, with mostly low -grade AEs and low treatment discontinuation rates ‒ There was no clinically meaningful increase in immune -related AEs • IMforte is the first Phase 3 study to show PFS and OS improvement with 1L maintenance treatment for ES-SCLC, highlighting the potential of lurbinectedin + atezolizumab to become a new standard of care for 1L maintenance therapy in patients with this aggressive and difficult-to-treat disease
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Clinical and Development Overview Rob Iannone, M.D., M.S.C.E. Executive Vice President, Global Head of Research and Development and Chief Medical Officer June 10, 2025
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June 10, 2025 Outcomes in first-line treatments of ES-SCLC need improvement1-8 1L = first line; 2L = second line; ES-SCLC = extensive-stage small cell lung cancer; ICI = immune checkpoint inhibitor; MOA = me chanism of action. 1American Cancer Society ®. Accessed February 10, 2025. Available from: What Is Lung Cancer? | Types of Lung Cancer | American Cancer Society ; 2Dingemans AC, et al. Ann Oncol. 2021;32(7):839-853; 3Siegel RL, et al. CA Cancer J Clin. 2025;75(1):10-45; 4Cramer-van der Welle et al. Eur J Cancer Care. 2020;29(5):e13250; 5Suri, G et al. Value in Health, 2024;27 (6): S149; 6Ramirez RA, et al. ASCO 2022 [abstract 8584]; 7Gerber DE, et al, J Clin Oncol. 2013;31(8):1009-1020; 8Liu SV, et al. J Clin Oncol. 2021;39(6):619-630; 9Santamaría Nuñez G, et al. Mol Cancer Ther. 2016;15(10):2399-2412; 10Belgiovine C, et al. Br J Cancer. 2017;117(5):628-638; 11Dumoulin DW, et al. Eur J Cancer. 2022;172:357-366; 12Calles A, et al. Mol Cancer Ther. 2024; [Published online December 5, 2024]; 13Chakraborty S, et al. Cell Rep Med. 2024;5(12):101852; 14Liu SV, et al. J Clin Oncol. 2021;39(6):619-630; 15Reck M, et al. J Thorac Oncol. 2022;17(9)1122-1129; 16Trigo J, et al. Lancet Oncol. 2020;21(5):645-654; 17Paz-Ares, et al. ASCO 2025. MoA of lurbinectedin and preclinical evidence support the combination of lurbinectedin and ICIs9-13 Combining atezolizumab with lurbinectedin in maintenance is supported by substantial evidence of efficacy and safety of the individual agents in 1L and 2L settings14-17 Adding lurbinectedin to atezolizumab in the maintenance phase demonstrated improved outcomesfor patients with ES-SCLC17 IMforte Data Brings Meaningful Improvement to 1L ES-SCLC Patients 26
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June 10, 2025 IMforte Data Represents Potential to Shift 1L ES-SCLC Treatment Paradigm 27 sNDA granted Priority Review with October 7, 2025, PDUFA target date Simultaneous publication in The Lancet IMforte data presented at ASCO ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guideli nes in Oncology (NCCN Guidelines®); PDUFA = Prescription Drug User Fee Act; sNDA = supplemental New Drug Application IMforte data submitted to NCCN
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Commercial Overview Samantha Pearce Executive Vice President, Chief Commercial Officer June 10, 2025
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June 10, 20251L = first-line; 2L = second-line. 1Internal analysis of incidence rates from SEER and NPCR databases, 2023 submission (2001 -2021) (Release: June 2024); 2SHS claims data ending September 2024;Tx Onc data ending October 2024; Onmark Unity Data ending October 2024; IntrinsiQ ION data ending October 2024. Zepzelca eligible population SCLC Newly Diagnosed Patients (~30K)1 Limited Stage (LS) (30%)2 Non-IO Treated Extended Stage (ES) (70%)2 Treated with Immuno-Oncology (IO) agents Disease Progression Maintenance Therapy Eligible Receives Maintenance Therapy - IO +/- Zepzelca No Maintenance Zepzelca-Naïve Eligible Patients - 2L+ Chemoradiotherapy +/- IO First-Line Use Drives Zepzelca Growth Opportunity 1L SCLC2L+ SCLC 29
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June 10, 20251L = first-line; 2L = second-line; ES-SCLC = extensive-stage small cell lung cancer; SCLC = small -cell lung cancer. Source: Paz-Ares, et al. ASCO 2025. 1Pending regulatory approval. IMforte Data Support Use of Zepzelca as a Foundational SCLC Treatment 2 3 Continued Use in 2L+ Zepzelca-Naïve Patients Establish Zepzelca as 1L Treatment of Choice in Maintenance Setting1 1 Drive Further Adoption of 1L Maintenance Regimen • Educate prescribers and patients on the benefits of receiving maintenance therapy, which can result in prolonged survival • Maintenance options, including Zepzelca combination, are well tolerated • Practice-changing data from combination of Zepzelca + atezolizumab improved survival outcomes for patients with 1L ES-SCLC • Zepzelca + atezolizumab showed a manageable safety profile in patients • Limited-stage patients remain eligible for treatment with Zepzelca once progression occurs • Important treatment option for Zepzelca-naïve patients in later lines of therapy 30
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June 10, 2025 Thank You