Novartis ESMO Event Presentation

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#1YYYYYYYY AYYAYYAYAY YYYYYYYY AYYAY YYLYY AYYAY Novartis Investor Relations ATTAT YYAYY AYYAY YYLYY LYYLY YYAYY LYYLY YYAYY AYYAY YYAYY LYYLY YYYY LYYLY YYAYY AYYAY LY LYYAYYAYAY YAYYYY YAYYYY YY. AYY YY YAYAY YYY YY YAYYYY AYYAYYAYAY YYYYYYYY AYYAYYAYAY AYY YY YY YAYYYY YAYAY YYY AYAY YYY AYAY AYYYY Novartis ESMO Call Investor Presentation October 24, 2023 1 NOVARTIS | Reimagining Medicine#2Disclaimer This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as "potential," "will," "planned," "pipeline," "outlook," or similar expressions, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Pluvicto or any other investigational or approved products described in this presentation, or regarding potential future revenues from Pluvicto or any other investigational or approved products described in this presentation. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Pluvicto or any other investigational or approved products described in this presentation will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Pluvicto or any other investigational or approved products described in this presentation will be commercially successful in the future. In particular, our expectations regarding Pluvicto or any other investigational or approved products described in this presentation could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this presentation as of this date and does not undertake any obligation to update any forward-looking statements contained in this presentation as a result of new information, future events or otherwise. All product names appearing in italics are trademarks owned by or licensed to Novartis Group companies. 2 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#3Participants Shreeram Aradhye, MD President, Development & Chief Medical Officer Jeff Legos, PhD EVP, Global Head of Oncology Development 3 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#4Agenda 1 Pluvicto potential across prostate cancer stages 2 Pluvicto PSMAfore results 3 Q&A 4 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#5Prostate cancer is the second most common cancer in men worldwide 1.4 million Prostate cancer cases worldwide per year 30% 5-year survival prognosis for mCRPC patients +4 months median OS benefit from current SoC seen in VISION study SoC heavily reliant on hormonal therapies (castration) >375k Prostate cancer deaths per year WW Source: Wang L. Et all, Front. Public Health, 16 February 2022 (Frontiers | Prostate Cancer Incidence and Mortality: Global Status and Temporal Trends in 89 Countries From 2000 to 2019 (frontiersin.org)) 5 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#6Ph3 VISION study: Pluvicto met both primary endpoints of rPFS and OS in the mCRPC post-taxane setting, as published in NEJM1 Reduced risk of progression or death by 60% rPFS HR: 0.40 (99.2% CI: 0.29, 0.57), p<0.001 (one-sided) Median rPFS, months: 8.7 vs. 3.4 Reduced risk of death by 38% OS HR: 0.62 (95% CI: 0.52, 0.74), p<0.001 (one-sided) Median OS, months: 15.3 vs. 11.3 Event-free probability (%) 100 90 80 70 60 50 SoC alone 177 Lu-PSMA-617 + SoC 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Time from randomization (months) Event-free probability (%) 60 40 30 85432 100 90 80 70 50 SoC alone 177 Lu-PSMA-617 + SoC 20 10 0 0 2 4 6 Number still at Risk 177 Lu-PSMA-617+ SoC 385 373 362 292 272 235 215 194 182 146 137 121 88 83 71 51 49 37 21 18 Number still risk SoC alone 196 146 119 58 36 26 19 14 14 13 13 11 7 7 7 4 3 3 2 2 0 6 1 1 0 0 0 0 177Lu-PSMA-617+ SoC 551 535 SoC alone 280 238 506 470 203 173 425 377 332 289 236 166 112 155 133 117 98 22 8 10 12 14 16 18 20 22 Time from randomization (months) 63 24 26 28 30 32 333 51 33 16 33 0 O 0 20 50 15 52 369 865 1. Sartor, N Engl J Med 2021;385:1091-103 6 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#7Pluvicto approved in 37 countries including US and EU; RoW submissions ongoing FDA indication statement PLUVICTO is a radioligand therapeutic agent indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. More than 7,400 patients treated across 37 countries1 US Other selected countries + EU 1. In commercial setting 7 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#8Ambition to transform advanced prostate cancer across four main segments with Pluvicto studies 4 PSMA-DC 3 PSMAddition 2 PSMAfore 1 VISION Local PC US: 283k BCR US: 41k Localized Locoregional nmCRPC US: 33k Locoregional m HSPC US: 39k mCRPC 1L US: 42k 2L+ US: 27k Metastatic Source: Cerner Enviza 2023 US Prostate Cancer Incidence PC = prostate cancer BCR biochemical recurrence nmCRPC = non-metastatic castration-resistant prostate cancer mCRPC metastatic castration-resistant prostate cancer 8 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION mHSPC metastatic hormone-sensitive prostate cancer NOVARTIS | Reimagining Medicine#9PSMAfore met primary endpoint¹ with clinically meaningful and highly statistically significant rPFS benefit in pre-taxane setting 1 Pluvicto demonstrated robust efficacy... ✓ More than doubled median rPFS2 Consistent benefit across subgroups² ✓ Improved QoL compared to daily oral ARPI² ✓ Pre-specified crossover-adjusted OS analysis HR 0.802 2 ... with a favorable safety profile Lower rate of Grade ≥3 AEs compared to daily oral ARPI Low rate of AE-driven discontinuations ✓ Fewer patients required dose adjustment Even better tolerability than in VISION 1. Primary rPFS analysis based on centrally confirmed rPFS events with Oct. 2022 data cutoff. 2. Updated rPFS analysis (at time of 2nd interim OS analysis) based on Jun. 2023 data cutoff. 9 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#10Agenda 1 Pluvicto potential across prostate cancer stages 2 Pluvicto PSM Afore results 3 Q&A 10 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#11PSMAfore study design Eligible adults Confirmed progressive mCRPC ≥ 1 PSMA-positive metastatic lesion on 68Ga-PSMA-11 PET/CT and no exclusionary PSMA-negative lesions Progressed once on prior second-generation ARPI • Candidates for change in ARPI ■ Taxane-naive (except [neo]adjuvant > 12 months ago) - Not candidates for PARP inhibition ECOG performance status 0-1 11 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION 177Lu-PSMA-617 7.4 GBq (200 mi) + 10% Once every 6 weeks for 6 cycles 1:1 N = 468 Crossover allowed upon centrally confirmed radiographic progression Safety follow-up Long-term follow-up Androgen receptor pathway inhibitor (ARPI) change - abiraterone or enzalutamide Randomization stratification factors Prior ARPI setting (castration-resistant vs. hormone-sensitive prostate cancer) BPI-SF worst pain intensity score (0-3 vs. >3) NOVARTIS | Reimagining Medicine#12PSMAfore was specifically designed to address key unmet needs in mCRPC Dosing regimen Choice of comparator Crossover design Insights Low kidney uptake enables 6 cycles of Pluvicto at 7.4 GBq, already proven in the sicker post-taxane setting Many patients unwilling or ineligible to take taxane-based chemotherapy, due to debilitating side effects Strong results in VISION increased risk of dropout in PSMAfore control arm PSMAfore trial design Maintain dosing regimen for pre-taxane population to optimize radiation delivery Compare to change in ARPI, to potentially allow patients to reduce, eliminate or delay chemo Study allowed patients on control arm to receive Pluvicto after centrally confirmed radiographic progression Pre-specified primary OS analysis adjusted for crossover because of this confounding factor 12 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#13PSMAfore analysis plan rPFS ㅏ OS PRIMARY ENDPOINT rPFS BICR per PCWG3/ RECIST v1.1 Primary Updated KEY SECONDARY ENDPOINT OS prespecified for RPSFT crossover-adjusted analysis 1st interim 2nd interim 3rd interim Other secondary endpoints rPFS2 ■ Time to soft tissue progression PFS, PFS2 PSA50 Time to SSE Time to chemotherapy ■ HRQoL Safety and tolerability 13 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION Exploratory endpoints ☐ ORR, DCR, DOR Time to PSA progression ■ Time to pain progression Biomarker associations Final NOVARTIS | Reimagining Medicine#14Baseline patient characteristics similar between the two arms and representative of intended population 177Lu-PSMA-617 (n = 234) ARPI change (n = 234) Age, years, median (range) 71 (43-94) 72 (53-91) White, n (%) 211 (90.2) 214 (91.5) ECOG performance status 0 146 (62.4) 115 (49.1) n (%) 1 86 (36.8) 114 (48.7) Gleason score 8-10, n (%) PSA, median (range), µg/L Haemoglobin, median (range), g/L Alkaline phosphatase, median (range), U/L Lactate dehydrogenase, median (range), U/L Site of disease n (%) Prior ARPI n (%) 129.0 (88-156) 103.5 (28-1319) 196.5 (124-999) 7 (3.0) Liver Lymph node 76 (32.5) 74 (31.6) Bone 205 (87.6) 203 (86.8) Abiraterone Enzalutamide 119 (50.9) 130 (55.6) 94 (40.2) Other 21 (9.0) 84 (35.9) 20 (8.5) 136 (58.1) 18.4 (0-1197) 128.0 (88-155) 100.0 (36-1727) 197.0 (66-1314) 13 (5.6) 107 (45.7) 14.9 (0-4224) 14 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#15Pluvicto showed a clinically meaningful and highly statistically significant rPFS benefit in taxane-naive patients with PSMA+ mCRPC Primary¹ HR: 0.41 (95% CI: 0.29, 0.56); p < 0.0001 Updated HR: 0.43 (95% CI: 0.33, 0.54); p < 0.0001 (nominal) 88 100 Event-free probability (%) 80 60 60 40 40 20 20 177Lu-PSMA-617 ARPI change 0 T 0 2 4 6 8 10 12 14 16 18 Time from randomization (months) Number of patients still at risk T -0 20 22 234 216 174 234 197 126 150 125 79 25 65 82 36 64 21 45 12 20 10 2 0 8 4 1 0 177Lu-PSMA-617 (n = 234) Events, n 115 (49.1%) ARPI change (n = 234) 168 (71.8%) Median rPFS (95% CI) 12.0 months (9.3, 14.4) 5.6 months (4.2, 6.0) 1. Primary rPFS analysis based on centrally confirmed rPFS events with Oct. 2022 data cutoff. 2. Updated rPFS analysis (at time of 2nd interim OS analysis) based on Jun. 2023 data cutoff. 15 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#16Benefit¹ was consistent across pre-specified subgroups² HR 95% CI All patients Previous ARPI setting Symptomatology Liver metastases at baseline Baseline PSA level 0.43 0.33, 0.54 CRPC ✓ HSPC 0.40 0.30, 0.52 0.57 0.33, 0.98 Asymptomatic or mildly symptomatic 0.40 0.30, 0.53 ✓ Symptomatic 0.51 0.32, 0.79 ✓ Yes 0.42 0.11, 1.61 ✓ No 0.43 0.33, 0.55 <median 0.42 0.29, 0.60 ≥ median 0.40 0.29, 0.56 Initial Gleason score < 6 0.55 0.10, 3.09 ≥ 6 0.42 0.32, 0.54 Baseline LDH level ≤ 260 IU/L 0.41 0.31, 0.54 > 260 IU/L 0.53 0.27, 1.07 Previous ARPI Abiraterone Enzalutamide 0.47 0.33, 0.66 0.35 0.24, 0.52 1. rPFS per BIRC HR for Pluvicto vs. ARPI change 2. Subgroups with <10 patients in both arms include liver mets at baseline (yes) and initial Gleason score < 6 16 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#17PSA50 response was >2.5X more frequent with Pluvicto than with ARPI change among evaluable patients Waterfall plots of best percentage change from baseline in PSA 100 177 Lu-PSMA-617 (n = 213) ARPI change (n = 221) Best percentage change in PSA from baseline (%) 86220 40 -20 -40 -60 -80 -100 17 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION Confirmed decrease ≥ 50%: 57.6% Confirmed decrease ≥ 50%: 20.4% NOVARTIS | Reimagining Medicine#18Pluvicto halved the number of symptomatic skeletal events (SSE)1 and prolonged time without SSE vs. ARPI change 177 Lu-PSMA-617 (n = 234) Number of events, n (%) SSE Death 25 (10.7) 21 (9.0) ARPI change (n=234) 59 (25.2) 54 (23.1) 4 (1.7) Median time to SSE, months (95% CI) NE (NE, NE) 5 (2.1) NE (15.6, NE) HR (95% CI) 0.35 (0.22, 0.57) 1. SSE defined as the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause 18 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#19Proportion of patients (%) Objective response rate (ORR) was higher and duration of response (DOR) was longer with Pluvicto versus ARPI change¹ 177 Lu-PSMA-617 (n = 71) ARPI change (n = 74) 21.1 2.7 45.9 32.4 31.0 29.6 12.2 15.5 Complete response Partial response Stable disease Progressive disease Best ORR in soft tissue per RECIST v1.1 ORR in soft tissue: 50.7% vs. 14.9%2 Median DOR in soft tissue³, months: 6.8 2.8 13.6 vs. 10.14 Unknown 1. Among patients with measurable disease at baseline. 2. 95% CI: 50.7% (38.6, 62.8) vs. 14.9% (7.7, 25.0) 3. In patients with complete response or partial response 4. 95% CI: 13.6 (11.6, NE), n = 36 vs. 10.0 (4.6, NE), n = 11 19 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#20Patients on Pluvicto demonstrated improved quality of life compared to daily oral ARPI FACT-P total score 1 HR: 0.59 (95% CI: 0.47, 0.72) 100 80 Event-free probability (%) 60 60 40 20 177 Lu-PSMA-617 ARPI change BPI-SF pain intensity scale2 HR: 0.69 (95% CI: 0.56, 0.85) 100 80 Event-free probability (%) 60 60 60 420 20 177 Lu-PSMA-617 ARPI change 0 2 4 6 8 10 12 14 L6 T T 16 18 20 0 2 4 6 8 10 12 14 16 18 20 Time from randomization (months) Time from randomization (months) Number of patients still at risk 43 96 234 199 160 130 101 38 12 234 174 115 64 39 20 7 8 32 95 27 1 0 234 190 138 108 88 39 12 2 0 234 159 105 61 42 24 82 1. FACT-P: Median time to worsening, months (95% CI): 7.5 (6.1, 8.5) vs. 4.3 (3.5, 4.5) 2. BPI: Median time to worsening, months (95% CI): 5.0 (4.4, 6.9) vs. 3.7 (3.1, 4.4) 20 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION 1 0 2 0 NOVARTIS | Reimagining Medicine#21Overall survival data interpretation confounded by crossover Crossover: 123/146 (84%) patients who discontinued with radiographic progression 45% information fraction at time of 2nd interim OS analysis Randomized to ARPI N=234 Treatment discontinued N=193 Discontinued due to radiographic progression N=146 Treated with ARPI N=232 Treatment ongoing N=39 OS HR 95% CI Pre-specified primary crossover-adjusted 0.80 (0.48, 1.33) analysis Unadjusted ITT 1.16 (0.83, 1.64) analysis Crossover to Pluvicto N=123 21 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#22ARDT NON-Crossover ARDT Crossover ARPI patients who crossed over to Pluvicto had a survival benefit over ARPI patients who did not cross over ARPI crossover patients (n=123) rPFS time OS time from rPD 0 10 12 14 16 22 24 Months ARPI non-crossover patients (n=111) Estimated OS probability at 12 months: 92.1% for pts randomized to ARPI arm who crossed over 68.6% for pts randomized to ARPI arm who did not cross over 0 2 8 10 12 Months 14 16 18 20 22 24 22 22 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#23Other than Pluvicto crossover and concurrent radiation, no major difference in post-progression therapies between treatments arms Antineoplastic therapy since discontinuation of study drug by medication type¹ Medication Type Pluvicto as crossover treatment 177Lu-PSMA-617 N=234 | n (%) ARPI N=234 | n (%) 0 123 (84.2) 36 (15.4) 66 (28.2) Radiation therapy Concurrent (includes crossover treatment) 7 (3.0) 39 (16.7) Post-study treatment 29 (12.4) 27 (11.5) ≥ 1 subsequent ANP medication (excluding crossover) 81 (34.6) 68 (29.1) 70 (29.9) 61 (26.1) Chemotherapy 13 (5.6) 4 (1.7) Hormonal therapy 5 (2.1) 2 (0.9) Biologic therapy Targeted therapy (excluding radioligand therapy) 2 (0.9) 3 (1.3) PSMA-directed radioligand therapy 1 (0.4) 5 (2.1) 1 (0.4) 0 Other 1. Full analysis set. A medication/therapy can appear with more than one medication type. Only ANP medications that started after the end of randomized treatment date are summarized. For crossover subjects all antineoplastic medications after crossover are included in the ARPI column. Targeted therapies reported: capivasertib, olaparib, and NUV-868 (BETI). PSMA-directed radioligand therapies reported: Pluvicto, 67CuBIPSMA. 23 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#24Treatment with Pluvicto had a favorable safety profile and was well tolerated 177 Lu-PSMA-617 ARPI change 63% of patients received 6 cycles of Pluvicto Lower rate of Grade ≥3 AES compared to daily oral ARPI Fewer patients on Pluvicto required a dose adjustment compared to ARPI AE-driven discontinuations were low and balanced between the arms Treatment-related Leading to dose adjustment Leading to discontinuation AES, n (%) (n = 227) (n = 232) Any 223 (98.2) 223 (96.1) Grade 3-4 77 (33.9) 100 (43.1) Serious 46 (20.3) 65 (28.0) Treatment-related 7 (3.1) 5 (2.2) Fatal (Grade 5) 4 (1.8) 5 (2.2) 0 1 (0.4) 8 (3.5) 35 (15.1) 13 (5.7) 12 (5.2) 24 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#25Vast majority of AEs were low-grade 177Lu-PSMA-617 (n = 227) 130 (57.3) Treatment-emergent adverse events in ≥ 10% patients in either arm AES, n (%) Dry mouth All grades ARPI change (n = 232) 5 (2.2) 177Lu-PSMA-617 (n = 227) 3 (1.3) Grades 3-5 ARPI change (n = 232) Asthenia Nausea 72 (31.7) 67 (28.9) 1 (0.4) 8 (3.4) 71 (31.3) 28 (12.1) 0 1 (0.4) Anaemia 55 (24.2) 39 (16.8) 14 (6.2) 14 (6.0) Fatigue 52 (22.9) 59 (25.4) 0 4 (1.7) Constipation 50 (22.0) 31 (13.4) 1 (0.4) 0 Decreased appetite 48 (21.1) 42 (18.1) 0 1 (0.4) Arthralgia 43 (18.9) 48 (20.7) 0 1 (0.4) COVID-19 37 (16.3) 26 (11.2) 1 (0.4) 1 (0.4) Diarrhoea 37 (16.3) 20 (8.6) 0 1 (0.4) Back pain 28 (12.3) 38 (16.4) 2 (0.9) 5 (2.2) 0 Vomiting 26 (11.5) 11 (4.7) 0 Oedema peripheral 19 (8.4) 26 (11.2) 0 Weight loss 15 (6.6) 28 (12.1) 2 (0.9) 0 5 (2.2) 25 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#26Exposure-adjusted safety data show even better tolerability in this earlier line of treatment than was seen in the VISION study Incidence rate per 100 subject-time years PSMAfore Incidence rate per 100 subject-time years VISION 60 88 39 53 AES (Grade ≥3) Treatment related AEs (Grade ≥3) 17 SAES 33 ~2,000 patient-years of exposure in VISION, PSMAfore and post-marketing experience support favorable safety and tolerability profile of Pluvicto 26 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#27PSMAfore study showed robust efficacy with favorable safety of Pluvicto in PSMA+ mCRPC patients in the pre-taxane setting Robust efficacy rPFS1 Median rPFS2 PSA50 response Time to SSE ORR³ Pluvicto vs. ARPI arm HR 0.41 (0.29, 0.56) 12.0 vs. 5.6 months 57.6% vs. 20.4% HR 0.35 (0.22, 0.57) 50.7% vs. 14.9% HR 0.59 (0.47, 0.72) HR 0.69 (0.56, 0.85) Time to worsening (FACT-P4) Time to worsening (BPI-SF5) Crossover-adjusted OS HR 0.80 (0.48, 1.33) Favorable safety profile Vast majority of AEs low-grade Grade 3-4 AES: 33.9% Pluvicto vs. 43.1% ARPI SAES: 20.3% Pluvicto vs. 28.0% ARPI AEs leading to discontinuation6: 5.7% vs. 5.2% AEs leading to dose adjustment: 3.5% vs. 15.1% Overall exposure to Pluvicto ~2,000 patient-years (incl. VISION, PSMAfore and post-marketing experience) Unadjusted OS (84% crossover) HR 1.16 (0.83, 1.64) 1. Primary rPFS analysis based on 166 rPFS events per BICR assessment (or centrally confirmed rPFS events); 1-sided p-value: <0.0001. Updated analysis of rPFS (at time of 2nd interim OS analysis) was consistent, with HR 0.43 (0.33, 0.54). All other data points from updated analysis with more mature data. 2. (95% CI): 12.0 (9.3, 14.4) vs. 5.6 (4.2, 5.95) 3. ORR in soft tissue per RECIST 1.1 for pts with measurable disease at baseline; (95% CI): 50.7% (38.6, 62.8) vs. 14.9% (7.7, 25.0) 4. FACT-P: prostate cancer-specific quality of life 5. BPI-SF: severity of pain and impact of pain on daily functions 6. Comparisons for Pluvicto vs. ARPI arm 27 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#28Next steps for Pluvicto in the pre-taxane setting High crossover confounded OS analysis interpretation with 45% information fraction PSMAfore continues to next interim analysis for OS after ~75% of target events Submission to health authorities to follow in 2024 28 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine#29Agenda 1 Pluvicto potential across prostate cancer stages 2 Pluvicto PSMAfore results 3 Q&A 29 NOVARTIS ESMO EVENT | OCTOBER 24, 2023 | INVESTOR PRESENTATION NOVARTIS | Reimagining Medicine

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