ASCO 2026 Conference Intelligence

PFS2 Pitfalls & Promise In the context of these 3 trials, as designed "PFS2" is a dubious outcome measure with unclear endpoint definition Comparison of "PFS2" does not inform whether experimental therapy should be used in first-line vs later TFST, TSST have clear definitions, may provide insightful summary of the patients' experience across lines of therapy PFS=progression free survival; OS=overall survival; TFST=Time to first subsequent treatment or death; TSST=Time to second subsequent treatment or death 2026 ASCO #ASCO26 PRESENTED BY: Meredith M. Regan, ScD, FASCO ASCO MISICAN SOCIETY OF ANNUAL MEETING CUNICAL ONCOLDER Presentation is property of the author and ASCO. Permission required for reuse, contact permissors@asco.org org. KNOWLEDGE CONQUERS CANCER Summary 10.8 PFS by BICR 5.6 PFS by BICR: 0.57 (0.44-0.73) 9.6 PFS by investigator Dato-DXd ICC 5.2 PFS by investigator: 0.56 (0.47-0.67) 10.9 TFST 5.6 TFST: 0.49 (0.41-0.59) 15.6 PFS2 11.8 PFS2: 0.61 (0.50-0.74) 16.7 TSST TSST: 0.67 (0.55-0.81) 12.6 23.7 OS OS: 0.79 (0.64-0.98) 18.7 0 5 10 15 20 25 30 0 0.5 1 1.5 Median (months) Hazard ratio (95% CI)* Favors Dato-DXd Favors ICC Green and blue bars represent median values; error bars denote the 95% CI, calculated as the difference between the median and the lower bound (lower error) and between the upper bound and the median (upper error). "A 99% CI was used for the PFS by BICR HR and a 95.01% CI was used for the OS HR. BICR, blinded independent central review; CI, confidence interval; Dato-DXd, datopotamab deruxlecan; ICC, investigator's choice of chemotherapy; OS, overall survival; PFS, progression-free survival; PFS2, time to second progression or death; TFST, time to first subsequent therapy or death; TSST, time to second subsequent therapy or death. 2026 ASCO #ASCO26 PRE SENTED BY: David W. Cescon, MD, PhD ASCO AMERICAN SOCIETY or CURICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER Key Trial Design Features Heterogeneous Conditions Characteristic / endpoint TROPION Breast-02 ASCENT 03 ASCENT 04 Statistical testing, sample size PFS & OS PFS & OS PFS & OS OS Primary Key secondary Key secondary PFS-BICR (PD by RECIST) Primary Primary (real-time) Primary (real-time) PFS-INV (PD by RECIST) Secondary (real-time) Sensitivity Sensitivity Protocol imaging Until PD-INV Until PD-BICR Until PD-BICR (or death / WC, even if start 2L) (or death / WC / start 2L) (or death / WC / start 2L) +1 additional Subsequent imaging, follow-up Local standards, report q3m Local standards, report q3m Local standards, report q3m Subsequent treatment: Treatment beyond PD allowed? No Yes Yes Crossover for control group? No Yes, 2L SG (after PD-BICR Yes, 2L SG (after PD-BICR (provision of experimental as 2L tx) event & eligibility; 41%) event & eligibility; 35%) Agent available for 2L tx? No Yes Yes Other protocol guidance 2L tx? No No No Study clinical visits & imaging Clinical visits & imaging SOC Rando 1L study therapy PD Death Subsequent (2L+) therapy PFS OS Source publicly available protocol documents (see references). Abbreviations Rando-randomization; United line X, 2L=second line X tertherapy, discont-discontinue, PD-disease progression (by W-investigator, BICR-binded independent central review); WC=wthdrawn consent; q3m:every 3 months TFST Time to first subsequent treatment, TSST=Time to second subsequent treatment, SG-sactuzumab govtlecan, For % crossover, denominator n I rendomized. 2026 ASCO #ASCO26 PRESENTED BY: Meredith M. Regan, $cD,FASCO ASCO - ANNUAL MEETING SINCA - Presentation . property if the author and ASCO Permission - contact CONQUERS CANCER

Conclusions Denosumab Q12w is non inferior to Denosumab Q12w reduces drug Q4w for time to first SSE in costs by 53% per patient metastatic breast cancer or Denosumab Q12w after induction castration resistant prostate cancer phase is a new standard treatment patients with bone metastases (HR for patients with bone metastases 1.023; 90%Cl: 0.874-1.197) from breast cancer or castration Denosumab Q12w improved safety resistant prostate cancer profile significantly less hypocalcemia less ONJ/tooth infection 2026 ASCO #ASCO26 PRE SENTED BY: ROGER VON MOOS MD ASCO AMERICAN SOCIETY OF CONICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@as.co.org arg KNOWLEDGE CONQUERS CANCER

Key Takeaway Points/Conclusions 1 2 3 The best clinical QoL measures trials are designed should be a co- PROs should be part with the input of the of every clinical trial primary endpoint ultimate stakeholder: because if we can't the person with live better what's the cancer point? 2026 ASCO #ASCO26 PRESENTED BY: Kelly Shanahan, MD @stage4kelly ASCO AMERICAN SOCIETY or CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

Take-Aways, in the context of these trials as designed "PFS2" not meaningful measure of clinical benefit for patients Caution, false sense of parallel to PFS endpoint (misnamed for this design) No clarity of desired measure and definition Affected by myriad uncontrolled factors beyond study-designed PFS period Not demonstrated to be surrogate of OS for mTNBC Collaboration pharma, academia, regulatory, patients to define estimand(s), and use IPD to investigate definitions and surrogacy in this setting "PFS2" endpoint in this design context does not provide evidence of benefit of earlier use of experimental therapy in first-line VS later TFST, TSST preferable, having clear measure and definition Integrating TFST, TSST (and OS) within treatment group can provide further insight to participants experience across lines of therapy Abbreviations IPD=individual patient data 2026 ASCO ASCO AMERICAN #ASCO26 PRESENTED BY: Meredith M. Regan, ScD, FASCO CURICAL CHICOLOGY ANNUAL MEETING Presentation property of the author and ASCO Permission required for reuse contact permissions@ass.org KNOWLEDGE CONQUERS CANCER 2026 A PFS After Next Line of Treatment (PFS2) SG Chemo (n 279) (n 279) 100 PFS2 events, n 114 143 90 Median PFS2," months (95% CI) 18.2 (15.9-NR) 14.0 (12.5-17.4) 71% (95% CI, 65-76) 80 Stratified HR (95% CI) 0.70(0.55-0.90) Event-Free Probability (%) 70 60 52% (95% CI, 45-59) 50 40 59% (95% CI, 53-65) H 30 20 41% (95% CI, 33-48) H 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time (months) No. of Patients Still at Risk (Events) SG 279(0) 270 (8) 259 (18) 238 (37) 221 (51) 189(65) 156(78) 107 (93) 79 (104) 54 (109) 33 (111) 20 (113) 13(114) 4(114) 3(114) 0 (114) Chemo 279(0) 271 (6) 257 (18) 237 (36) 212(59) 178(79) 133 (106) 86 (126) 67 (127) 34 (136) 19 (140) 10 (142) 2(143) 0 (143) PFS2 was longer in the SG group compared with the chemo group despite the high rate of crossover in the chemo group, with a 30% reduction in risk of a PFS2 event with SG *PFS2 B defined as time from randomization to first documented progression on next line therapy per investigator assessment or death due to any cause, whichever occurred Int Chemo, chemotherapy HR hazard rabo, NR, not reached PFS2 progression free survival 2. SG sacturumab govtlecan 2026 ASCO #ASCO26 PRE SENIED BY: Sara M Tolaney, MD ASCO AMERICAN DUNICAL CHICOLOGY ANNUAL MEETING Presentation a property of the author and ASCO Permission required for - contact permissions@wasoo.org KNOWLEDGE CONQUERS CANCER 2026 ASCO ANNUAL MEETING

Select Phase III Trials RAS Inhibitors in PDAC Adjuvant, 1L Metastatic, 2L Metastatic...More Pending Trial Name Therapeutic Target N Disease Setting Status RASolute 303 Gem/nabP +/- Daraxonrasib, D PanRAS 900 1L metastatic Activated Q1 2026 PFS, OS NCT07491445 RASolute 304 Daraxonrasib PanRAS 500 Adjuvant Activated Q4 2025 DFS NCT07252232 RASolute 305 Zoldonrasib + chemo/Z KRAS G12D 1L melastatic PFS, os Pending 2026 RASolute 309 Zoldonrasib + Daraxonrasib KRAS G12D, panRAS 1L metastatic Pending 2026 mFFX/NALIRIFOX +/- Dispel KRAS G12D 1L metastatic 614 Activated Q1 2026 Setigrasib OS NCT07409272 Chemo +/- DAWN 303 1L metastatic KRAS G12D 588 Activated Q2 2026 INCB161734/Placebo OS, PFS, ORR NCT07522073 Gem/nabP +/- 1L metastatic Activated Q2 2026 MAPKeeper 301 Atebimetinib MEK, panRAS 510 OS NCT07562152 HRS-4642-302 Chemo +/- HRS-4642 KRAS G12D IL metastatic Activated Q4 2025 China GFH375-X1301 VS-7375 VS Chemo KRAS G12D 2L metastatic Activated Q4 2025 China 2026 ASCO PRESENTED BY: Eileen M. O'Reilly, MD, FASCO ASCO ANERICA GREA #ASCO26 CONQUE ANNUAL MEETING Presentation is property of the author and ASCO Permission required for were. contact permissions@asco.org

ASCO 2026 THORACIC ONCOLOGY Seven Key Studies Published Simultaneously in Leading Journals Event-free survival with adjuvant selpercatinib in stage IB-IIIA LBA3 The NEW ENGLAND RET fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial JOURNAL of MEDICINE Ivonescimab plus chemotherapy versus tislelizumab plus LBA4 chemotherapy in previously untreated advanced squamous non-small cell lung cancer: Overall survival results of the THE LANCET phase 3 HARMONi-6 trial Sunvozertinib monotherapy versus platinum-based chemotherapy 8500 as first-line treatment for advanced NSCLC with EGFR exon20ins: The NEW ENGLAND Primary analysis of a multinational phase 3 randomized study JOURNAL of MEDICINE (WU-KONG28) Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ 8502 ANNALS OF non-small cell lung cancer: 7-year update from the phase 3 CROWN study ONCOLOGY Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) 8506 versus pembrolizumab (P) as first-line treatment for PD-L1-positive THE LANCET advanced non-small cell lung cancer (NSCLC): Results from the randomized phase 3 OptiTROP-Lung05 study Randomized phase III study of nivolumab after surgery and R 8000 adjuvant chemotherapy in NSCLC (ECOG-ACRIN EA5142, JAMA ALCHEMIST) ABBV-706 as monotherapy and in combination with budigalimab 8008 in patients with relapsed/refractory (R/R) small cell lung cancer nature medicine (SCLC)

DAILY EXPRESS CAMPAIGNING FOR A BETTER BRITAIN express.co.uk MONDAY, JUNE 1, 2026 £2.10 DAILY E EXPRESS CHAMPIONS Get your JEWISH PEOPLE ARSENAL Arsenal ANDION papers for DON'T FEEL SAFE ON S SUNDAY&EXPRESS PAINT THE 99p a day S. FREE FAMILY PASS WITH "THE BEST IS TOWN RED FOR 6 MONTHS YET TO COME' SEE PAGE 35 SEE PAGE 3 NEW SUBSCRIBERS ONLY: TERMS & CONDITIONS APPLY) CANCER HOPE FOR MILLIONS AS DRUG DOUBLES SURVIVAL Experts' tears of joy BY HANNA GEISSLER Health Editor, in Chicago A DAILY pill can almost double survival I Dua! Pop princess ties times for patients with the deadliest at 'game-changing' common cancer - in a breakthrough hailed as a treatment revolution. knot with actor fiancé Pancreatic cancer sufferers on the drug lived pancreatic treatment for twice as long as those on chemotherapy. The "game-changing" pill's success is thought to be SEE PAGE 11 TURN TO PAGE 4 DAILY Mirror WIN £1,000 breakfree 5 holidays.co.uk prizes to VOUCHER Monday, June 1, 2026 £2.10 be won Terms and conditions apply SEE PAGE 14 After the heartache. a day of joy Arsenal Prem League parade yesterday. Inset, PSG defeat SEE PAGES 10,11&SPORT Arsenal Dua Lipa and actor Callum Turner held low-key do yesterday SEE PAGE 8 I DUA! Emirate Stars tie the knot DEADLIEST CANCER: NEW HOPE BY HANNA GEISSLER A NEW daily pill has been hailed as the PRECIOUS Holy Grail in fighting pancreatic cancer. Drug daraxonrasib doubled survival times for patients with the deadliest major cancer in a trial. giving them six months longer than those on chemo. Specialist Dr Rachna Shroff, right, said: "It's a game-changer. When I saw the data, cried." FULL STORY: PAGE 5 GIFT OF TIME 'Game-changing' pill helps double Expert says she cried after seeing survival times for pancreatic disease data for the 'Holy Grail' breakthrough

After today's session EMERALD-1 LEAP-012 TALENTACE EMERALD-3 Cam + Rivo N 616 (3 arms) 480 (2 arms) 342 (2 arms) 760 (3 arms) 423 (2 arms) Regimen Arm A: Durva + Placebo Pembrolizumab + Atezolizumab + Bev Arm A: STRIDE + Len Camrelizumab + Arm B: Durva + Bev Lenvatinib Arm B: STRIDE Rivoceranib Control Arm C: TACE + Placebo TACE + Placebo + TACE Arm C: TACE TACE + Placebo Placebo PFS (RECIST) 15.0m (A) vs. 8.2m (C) 14.6m vs. 10.0m 10.32m vs. 6.37m 13.0m (A) vs. 9.8m (c) 11.1m vs. 8.3m (HR=0.77) (HR=0.66) (HR=0.64) (HR=0.70) (HR=0.73) OS Not available Unlikely different Immature 39.5 vs. 34.7m Immature (press release) (HR=0.84) ORR (RECIST) 43.6% (Arm A) 46.8% vs. 33.3% 49.1% vs. 33.9% Not reported 60.3% vs. 45.5% 43.6% (Arm B) (mRECIST) 29.6% (Arm C) carcinoine dual for phone #, rendoment - -cement - patients with systemically information salety I ham EMERA phase candomized durvalumab 4 . what I resided issusterial participants with cardinoms Voget of . alone in I advanced or cardeons MAZO 2026 ASCO #ASCO26 PRE SENTED IIY: Stephen L. Chan MD ASCO CLINICAL ANNUAL MEETING author ASCO for permissions@as.org KNOWLEDGE CONQUERS Do we know the best regimen? Exploratory analysis: PFS in the first 175 participants STRIDE + L+ TACE vs TACE STRIDE + TACE vs TACE $ DE+L+TACE TACE STRIDE+TACE TACE" (n=175) (n=175) (n=175) (n=175) 100 Total PFS events, n (%) 125 (71.4) 140(80.0) 100 Total PFS events n (%) 123(70.3) 140(80.0) 90 Median PFS 13.1(11.0-17.7) 8.1 (6.5-10.2) 90 Median PFS months (95% CI) 12.9(10.2-15.9) months (95% CI) 1.1(6.5-10.2) 80 HR(95% CI) 0.66 (0 52-0.85) 80 HR (95% CI) 0.71 (0.56-0.91) Proportion of participants alive 70 PFS maturity: 75.7% Proportion of participants alive 70 PFS maturity: 75.1% and progression-free (%) 60 50 and progression-free (%) 60 50 40 40 30 30 20 20 STRIDE+L+TACE STRIDE+TACE 10 10 TACE TACE 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Time from randomization (months) Time from randomization (months) No. of participants at risk No. of participants at risk STRIDE+L+TACE 175 147 132 108 92 77 66 52 43 36 24 13 5 2 1 0 STRIDE+TACE 175 143 123 97 84 66 58 51 43 36 24 12 7 4 0 0 TACE 175 131 99 75 61 55 45 39 26 22 14 10 5 4 1 0 TACE 175 131 99 75 61 55 45 39 26 22 14 10 5 4 1 0 DC02 Feb 23. 2026 PFS was assessed by BICR per RECIST v1.1. in First 175 participants RECIST Hasponse evaluation Offeria in Solid Tumors 2026 ASCO #ASCO26 PIA SENTED BY: Stephen L. Chan MD ASCO AMERICAN SOCIETY DE CLINICAL CHOCLOGY ANNUAL MEETING Presentation property of the euthor and ASCO Permission required for reuse, contact permissions@as.co.o KNOWLEDGE CONQUERS CANCER Clinical Trials on post IO 2nd line treatment IMBRAVE251 Efficacy Cabozantinib Lenvatinib Regorafenib Atezo + Len/Sor Len/Sor Population Failed 1-2 lines of Failed 1 line of Atezo- Failed 1 line of Atezo- CR/PR/SD on 1st line Atezo-Bev regimen (containing Bev Bev IO) Median OS 9.9m 8.6m 10.5m 14.6m 12.5m Median PFS 4.1m 5.4m 3.5m 4.3m 4.8m ORR PR: 6.4% PR: 12% PR: 10% CR/PR 7.6% PR: 5.8% SD: 76.5% SD: 72% SD: 72.5% SD: 62% SD: 62% Reference Chan SL et al. J Hep Kim H et al J Hep Cheon J et al. Liver 2024 Cancer 2025 Vogel A et al. ASCO 2026 2026 2026 ASCO #ASCO26 PRE SENTED BY: Stephen L. Chan MD ASCO AMERICAN or CLINICAL CHOCLOGY ANNUAL MEETING Presentation property of the euthor and ASCO Permission required for rese, contact permissions@as.com org. KNOWLEDGE CONQUERS CANCER Current control: TKI (regorafenib, cabozantinib, HCC with progression Disease progression, and Lenvatinib) on first-line IO eligible for further systemic regimen treatment 30-40% IMBRAVE251: Empirical IO continuation + TKI is not working Disease progression, and ineligible for further systemic Oligoprogression, and eligible (? Novel treatment) treatment for locoregional treatment 50% 10-20% Palliative care ? Local treatment + ICI continuation

Timing of pCR among Immune+ patients EARLY ESCALATION EARLY ESCALATION Across all Blocks, AFTV AFTV 34 of 47 Immune+ R+ T-DXd BLOCK B BLOCK c patients (72%) N=47 N=25 N=5 achieved pCR Randomize preRCB preRCB Surgery Total Among patients who achieved pCR: Number exiting Block 22 20 5 47 Majority (62%) did Number Achieving pCR 21 12 1 34 so by end Block A Cumulative % of total 62% 97% 100% pCRs observed 97% achieved (21/34 pCRs) (33/34 pCRs) (34/34 pCRs) pCR by end Block B, without AC Surgery No AC 2026 ASCO #ASCO26 PRE SENTED BY: Ciara C. O'Sullivan, MB Bch BAO ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse: contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

ASCO 2026 GU Oncology, May 31. PROTEUS, perioperative androgen receptor inhibitor apalutamide plus androgen-deprivation therapy given before and after radical prostatectomy, high-risk localized prostate cancer. ABBV-969, first-in-human antibody-drug conjugate, metastatic castration-resistant prostate cancer previously treated with taxanes and PSMA radioligand therapy. COMPPARE, proton versus photon external-beam radiation, localized prostate cancer.

NEJM ASCO 2026 Perioperative apalutamide: 20% PROTEUS reduced risk of metastasis or death, 9x pCR rate Adjuvant selpercatinib: 83% LIBRETTO-432 reduction in recurrence or death (RET+ NSCLC) Daraxonrasib: 60% reduction RASolute 302 in risk of death VS chemo (2L PDAC) Superior OS + PFS VS Teclistamab Ph3 standard therapy (R/R myeloma) Sunvozertinib: mPFS 10.3 VS 7.5 mo, WU-KONG28 ORR 58.9% vs 31.1% (1L EGFR ex20 NSCLC) #ASCO26 NEJM

Current & Future Management of Stage I TNBC Current approach: tumor size + response as the only deciding factors pCR Observation T1c Neoadjuvant chemo SURGERY AC-T or TCb? RD Capecitabine or olaparib Tumor size (if gBRCAmut) T1b Consider adjuvant chemo AC-T, TC, or TCb? T1mic SURGERY Observation? T1a A possible future approach: tumor size + biomarkers + dynamic response assessment Response biomarkers Predicted CR pCR confirmed Short neoadjuvant Tumor size + biomarkers Average risk (TILs, gene signatures) chemo T1b/c + adverse biomarkers Predicted RD "Rescue" SURGERY TCb +/- ICI RD Capecitabine, olaparib chemo or AC (if not given pre-op) VIII AC x4? Ultra-low risk T1b/c + favorable biomarkers ....... T1a (any biomarkers) SURGERY Observation? Adapted from Idossa... Leon-Ferre, ASCO Educational Book 2026 2026 ASCO PRESENTED BY: Roberto Leon-Ferre ASCO AMERICAN SOCIETY OF #ASCO26 CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

D Chemotherapy-free survival in the overall study, ESR1m, and ESR1m not detected populations Overall study ESR1m ESR1m not detected Giredestrant SOC ET Giredestrant everolimus SOC ET+ Giredestrant everolimus SOC ET+ everolimus n. 183 everolimus everolimus everollmus na 190 n. 102 n.a 105 n = 81 n = 85 Events, a (%) 111 (60.7) 146 (76.8) Events, (%) 51 (50.0) 78(74.3) Events, n (%) 60 (74.1) 68 (80.0) Median, mo (95% CI) 11.10 (9.56, 12.68) 7.89 (6.93,9.46) Median, mo (95% CI) 12.58 (10.91, 18.66) 8.54 (7.10, 9.95) Median, mo (95% CI) 9.53 (7.39, 11.60) 7.20 (6.11, 9.49) HR (95% Ci) 0.61 (0.47, 0.78) HR (95% CI) 0.46 (0.32, 0.66) HR (95% CI) 0.80 (0.57, 1.14) 100 100 100 survival (%) 20- 40 80 80 20 Chemotherapy-free survival (%) 80 60 60 Chemotherapy-free survival (%) 60 40 40 20 0 0 0 3 6 0 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 30 Time (mo) 0 3 6 9 Time (mo) 12 15 18 No. at risk 21 24 27 30 No. at risk Gredestrant 183 165 131 104 69 verolmus 33 13 7 Giredestrant No. at risk Time (mo) 49 2 102 94 77 63 everolimus 41 22 10 4 4 1 Giredestrant 81 71 everolimus 54 41 28 CET . 27 23 9 SOC ET 3 1 190 157 112 78 44 29 crotimus 18 8 6 2 105 66 62 43 21 everolmus 11 4 2 1 SOC 85 71 everolimus 50 35 23 18 14 6 Data nd/or cutott antibody-drug July 16, 2025 conjugate Median or death follow from up: 18 any 4 mo cause, (giredestrant whichever . occurred overolimus). first 18.7 Ct, confidence mo (SOC ET interval overolimus). ESRfm HR ESRI estimates mutation; are ET, stratified endocrine Chemotherapy therapy HR, free hazard survival ratio; was mo, defined months; as SOC. the time standard-of-care from randomization to the start of the first chemotherapy 5 2 26 ASCO #ASCO26 PRESENTED BY: Komal L. Jhaveri, MD, FACP, FASCO NUAL MEETING Presentation a property of the author and ASCO Permission required for reuse, contact permissions@asco.org ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER Chemotherapy-free survival in the overall study, ESR and ESR1m not detected populations Date are - Key takeaway points/conclusions 1 2 3 PFS benefit with giredestrant + everolimus was sustained through the next subsequent line of therapy Subsequent therapies were Improved PFS2 and generally balanced across treatment chemotherapy-free survival were Giredestrant + everolimus showed: arms and representative of consistent with the favorable Improved PFS2 the current SOC OS data at interim os analysis1 Improved chemotherapy-free survival S2 was defined as the time from randomization to first progression on next-line therapy or death. Chemotherapy-free survival was defined as the time from randomization to the start of the first chemotherapy and/or antibody-drug conjugate or death fro cause, whichever occurred first Rfm, ESR1 mutation; OS, overall survival; PFS, progression-free survival; PFS2, progression-free survival 2; SOC, standard-of-care. layer EL, of al. ESMO 2025 (oral LBA16). ASCO PRESENTED BY: Komal L. Jhaveri, MD, FACP, FASCO #ASCO26 ASCO AMERICAN SO CLINICAL ONC AL MEETING Presentation is property of the author and ASCO. Permission required for reuse; contact permissions@asco.org. KNOWLEDGE CONQUERS C.

TABLE 3. Summary of Data With Approved BCMA-Directed CAR T-Cell Therapy in Late Line Relapse Ide-Cel (KarMMa) Cilta-Cel (CARTITUDE-1) Population/Subgroup ORR, % >CR, % DoR Median PFS Median ORR, % >CR, % DoR, % PFS at 24m, % Total 73 33 11 m 9 m 98 82 NR 71 HR cyto 69 31 10.7 m 8.2 m 100 NA 20 m 48 ISS III NA NA NA NA NA NA NA NA R-ISS III 48 10 6.9 m 4.9 m 100 NA 13.8 m NA EMD 70 24 9 m 7.9 m 100 NA 12.9 m 47 BMPC > 50% 71 29 10.4 m 7.5 m 95 NA NA 51 NOTE. Outcomes in selected populations. Abbreviations: BMPC, bone marrow plasma cell infiltration; CR, complete response; DoR, duration of response; EMD, extramedullary disease; HR cyto, high-risk cytogenetics; ISS, international staging system; NA, not available; ORR, overall response rate; Penta-refractory, penta-drug refractory; PFS, progression-free survival; R-ISS, revised international staging system.

Key takeaway points/conclusions 1 2 3 PFS benefit with giredestrant + everolimus was sustained through the next subsequent line of therapy Subsequent therapies were Improved PFS2 and generally balanced across treatment chemotherapy-free survival were Giredestrant + everolimus showed: arms and representative of consistent with the favorable Improved PFS2 the current SOC OS data at interim os analysis¹ Improved chemotherapy-free survival PFS2 was defined as the time from randomization to first progression on next line therapy or death Chemotherapy-free survival was defined as the time from randomization to the start of the first chemotherapy and/or antibody-drug conjugate or death from any cause, whichever occurred first ESR1m ESR1 mutation OS, overall survival PFS, progression free survival PFS2, progression free survival 2; SOC, standard-of-care 1. Mayer EL of al ESMO 2025 (oral LBA16) 2026 ASCO #ASCO26 PRE SENTED BY: Komal L. Jhaveri, MD, FACP, FASCO ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER evERA BC study design A global, randomized, open-label, Phase III trial Enrollment period: August 2022 to October 2024 Key eligibility criteria* N = 373* ER+, HER2- aBC (1-3L of therapy) Giredestrant 30 mg PO QD + ≤2 prior lines of ET in the aBC setting everolimus 10 mg+ Until PD R or PD or relapse during/post-CDK4/6i + ET 1:1 unacceptable SOC ET$ No prior chemotherapy in the aBC setting toxicity + everolimus 10 mg+ Measurable disease per RECIST v1.1 or 5 Exemestane/fulvestrant/tamoxifen evaluable bone metastases I Alcohol-free dexamethasone mouthwash (0.5 mg/5 mL) prophylaxis and treatment of stomatitis was strongly recommended (10 mL swished for 2 minutes and spat QID) starting concurrently with . Trial was enriched to 55% of patients with ESR tumors at baseline study treatment for 8 weeks, and then reactively thereafter with the first appearance of symptoms (centrally tested via circulating tumor DNA) 1 Patients had to receive 2 6 months of CDK4/6i + ET in the aBC setting to be eligible for enrollment; prior fulvestrant was allowed Co-primary endpoints (RECIST v1.1) INV-PFS in patients with ESR1m tumors Stratification factors INV-PFS in the overall study population Prior treatment with fulvestrant (yes VS no) Key secondary endpoints Exploratory endpoints ESR 1m tumor (yes VS no/indeterminate) OS PFS2 Site of disease (visceral [lung and/or INV-ORR, DoR Chemotherapy-free survival liver involvement] VS non-visceral) Post-progression treatment ClinicalTrials gov number, NCT05306340 Adapted from Mayer EL, of at ESMO 2025 (oral LBA16), with permission I Defined as the time from randomization to first progression on next-line therapy or death 1 Defined as the time from randomization to the start of the first chemotherapy and/or antibody-drug conjugate or death from any cause, whichever occurred first 1-3L, first to third line, (a)BC, (advanced) breast cancer, CDK4/6i, cyclin-dependent kinase 4/6 inhibitor, DoR, duration of response, ER+, estrogen receptor-positive; ESRfm ESRf-mutated ET, endocrine therapy HER2- HER2-negative INV, investigator-assessed, ORR, objective response rate OS, overall survival, PD, progressive disease, PFS, progression free survival; PFS2, progression- free survival 2, PO, orally, QD, once daily, QID, four times daily, R, randomization RECIST, Response Evaluation Criteria in Solid Tumours SOC, standard-of-care 1. Rugo HS, et at Lancet Oncol 2017: 18:654-662 2026 ASCO #ASCO26 PRESENTED BY: Komal L. Jhaveri, MD, FACP, FASCO ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER PFS2 in the overall study, ESR1m, and ESR1m not detected populations Overall study ESR1m ESR1m not detected Giredestrant SOC ET+ Giredestrant SOC ET+ Giredestrant SOC ET everolimus everolimus everolimus everolimus everolimus everolimus n = 183 n= 190 n = 102 n * 105 n= 81 n= 85 Events, (%) 81 (44.3) 108 (56.8) Events, (%) 39 (38.2) 57 (54.3) Events, (%) 42 (51.9) 51 (60.0) Median, mo (95% CI) 19.02 (15.51, NE) 13.17 (11.70, 15.87) Median, mo (95% CI) 19.02(15.51,NE) 12.94 (11.76, 17.61) Median, mo (95% CI) 17.25 (13.01, NE) 12.88 (9.76, 20.83) HR (95% CI) 0.69 (0.51, 0.92) HR (95% CI) 0.61 (0.40, 0.93) HR (95% CI) 0.77 (0.51,17) 100 100 100 80- 80 80 60- 60 60 PFS2 (%) PFS2 2 PFS2 (%) 40 40 40 20- 20 20 0- 0 0 0 3 6 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 30 Time (mo) Time (mo) Time (mo) No. at risk No. risk No. risk Giredestrant 183 173 156 129 100 74 48 21 11 3 Garedestrant 102 96 85 72 50 30 15 6 5 2 Garedestrant 01 77 71 57 50 44 33 15 6 1 everolmus everolimes everolimus SOCET 190 177 157 121 87 58 38 18 8 1 SOCET 105 99 89 66 45 21 5 3 1 SOCET 85 78 68 55 42 37 30 15 7 1 everolmus everolimen everotmus Data cutoff July 16. 2025 Median follow 18 4 mo (giredestrant . everolimus), 18 mo (SOC ET everolemus) HR estimates are stratified PFS2 aus defined as the time from randomization to first progression on next line therapy or death CI, confidence interval, ESRfm, ESRf mutation ET, endocrine therapy HR hazard ratio, mo, months; NE not evaluable PFS2 progression free survival 2; SOC standard of care 2026 ASCO #ASCO26 PRE SENTED BY: Komal L. Jhaveri, MD, FACP, FASCO ASCO AMERICAN SOCIETY of CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for rever, contact permissions@ason.org KNOWL EDGE CONQUERS CANCER At interim OS analysis,¹ favorable OS was consistent with prolonged PFS2 and chemotherapy-free survival Overall study ESR1m ESR1m not detected Giredestrant SOC ET+ Giredestrant SOC ET+ Giredestrant SOC ET+ everolimus everolimus everolimus everolimus everolimus everolimus n= 183 n * 190 n = 102 n * 105 81 n * 85 Events, (%) 47 (25.7) 68 (35.8) Events, (%) 26 (25.5) 41 (39.0) Events, (%) 21 (25.9) 27 (31.8) Median, mo (95% CI) NE (NE, NE) 26.87 (22.21, NE) Median, mo (95% CI) NE(20.17,NE) 21.03 (14.78, 26.87) Median, mo (95% CI) NE (NE, NE) NE (27.01,NE) HR (95% CI) 0.69 (0.47, 1.00) HR (95% CI) 0.62 (0.38, 1.02) HR (95% CI) 0.79(0.44,1.40) 100 100 100 80- 80 80 60 60 60 OS (%) os (%) os (%) 40 40 40 20 20 20 0 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 6 9 12 15 18 21 24 27 30 33 36 Time (mo) No. risk Time (mo) Time (mo) No. risk No. risk Garedestrant 183 174 161 152 127 103 75 36 20 5 Giredestrant Gredestrant 102 % 87 81 57 37 19 8 6 2 81 78 74 71 70 66 56 28 14 3 everolimus everolimus everolimus SOCET 190 180 167 148 122 92 67 38 19 7 1 SOCET+ 105 100 50 3 57 33 55 to 3 1 SOCET 8 80 74 $ 65 59 49 26 16 6 1 everolimus everolmus everolimus Data cutoff July 16, 2025 Median follow up 18 mo (giredestrant . everolimus) 18 mo (SOC ET everolemus) HR estimates are stratified Figures reproduced from Mayor EL of at ESMO 2025 (oral LBA16) with permission CI, confidence interval, ESRfm, ESR1 mutation, ET, endocrine therapy, HR, hazard ratio, mo, months NE, not evaluable OS, overall survival PFS2, progression free survival 2. SOC, standard of-care Mayer EL, of or ESMO 2025 (oral LBA16) 2026 ASCO #ASCO26 PRI SENTED BY: Komal L. Jhaveri, MD, FACP, FASCO ASCO AMERICAN CURICAL ONCOLDGY ANNUAL MEETING Presentation property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER 2026 AS

Manageable CAR-T cell toxicities support outpatient dosing CRS (N=18) ICANS, delayed neurotoxicity (N=18) Dose n Median day Median Grade Grade Dex Toci Event, n Grade 1-2 Grade ≥3 level of onset, duration, 1-2 ≥3 (n, %) (n,%) (IU/kg) day days (n,%) (n,%) ICANS 1 1 (min, max) (min, max) 2 x 10⁷ 3 9.5(9-10) 2.5 (2-3) 2(67) 0 (0) 2 (67) 2(67) Delayed neurotoxicity (Parkinsonism, cranial 6 10⁶ 8 13(12-18) 3(1-8) 6(75) 0 (0) 3(36) 5(63) 0 nerve palsy, peripheral 0 4 10⁶ 7 13(5-14) 3 (3-5) 7(100) 0 (0) 5(71) 7(100) neuropathy) CRS were consistent with ex vivo CAR-T therapies, One Grade 3 ICANS was managed with with later onset supportive of outpatient dosing methylprednisolone and anakinra; limited to 3 days All events were Grade 1-2 and manageable with standard supportive care No delayed neurotoxicity observed in any patient AR, chimeric antigen receptor; CRS, cytokine release syndrome; dex, dexamethasone; DL, dose level; ICANS, immune effector cell-associated neurotoxicity syndrome; toci, tocilizumab. inMMyCAR KLN-1010 demonstrated a favorable toxicity profile Grade ≥3 cytopenias (N=18) Infusion-related reactions (N=18) Occurring post-infusion, Median time to resolution, Pre-dexamethasone Post-dexamethasone n (%) days (range) premedication premedication Patients, n 5 Neutropenia 13 11 (61%) 3 (1-9) Any IRR, n (%) 3 (60%) 0 (0%) Thrombocytopenia 6 (33%) 5.5 (2-7) Grade ≥3 IRR, n Anemia 1 0 4 (22%) 2 (1-7) Grade ≥3 infections No IRRs were observed following implementation of Early (≤M3) (N=18) Late (>M3) (N=8) dexamethasone premedication Grade >3, n 0 1 Favorable safety profile for outpatient dosing with a Types low number of events overall Pneumonia No events of EC-associated enterocolitis were observed adverse events were coded ents chimeric infections reaching antigen occurred the respective receptor: sMonth using IEC, visit 3 post-infusion: immune with MedDRA available effector v28.0. late laboratory Infections cell; Infections IRR, assessments infusion-related shown occurred include >Month at data all reaction. treatment-emergent 3. cutoff Prolonged (N=18 cytopenia total dosed). adverse was defined events mapped as Grade to >3 the not Infections resolved and by M1 infestations post-infusion, System based Organ on laboratory Class (SOC), values, regardless graded of per investigator-assessed CTCAE v5.0. M1 and relationship M2 evaluable to populations study treatment. MMyCAR include

Deep, ongoing BM MRD-negative responses observed Dose (IU/kg) ORR (N=18) MRD-negative BM responses (n=14) 2 107 100% 100 100% (n=6) 100 22% 20 % of MRD-evaluable patients 80 % of all patients 80 22% 67% 60 60 100% 40 40 6 X 10⁶ 50% 20 33% + 0 0 P Patients with All patients 24 mo follow-up MRD-negative 10⁻⁵ P PR VGPR CR sCR or deeper Median duration of follow-up: 2.8 months sBCMA (n=9) sFLC (n=16) 50 50 SD PR VGPR CR sCR Best change from baseline (%) 25 25 4 X 10⁶ MRD-negative 10⁻⁶ MRD-negative 10⁻⁵ 0 0 P MRD-negative 10⁻⁵ (Indeterminate 10-6) MRD positive -25 -25 P P MRD pending Progression Response ongoing -50 Best change from baseline (%) -50 -75 -75 0 1 2 3 4 5 6 7 8 9 10 11 12 -100 -100 Months post treatment Patients Patients MRD indeterminate at 10° includes NGS result pending or indeterminate. Bone marrow biopsy performed M1, M3, M6, M12, M18, and M24. BM, bone marrow; CR, complete response; D, study day; IU, infectious unit; M, study month; MRD, minimal residual disease; NGS, next generation sequencing; ORR, overall response rate; PR, partial response; CR, stringent complete response; BCMA, soluble B-cell maturation antigen; 50, stable disease; sFLC, serum free light chain; VGPR, very good partial response. MRD-negative BM responses reported in n ᵒ 13 patients with at least one evaluable post-treatment bone marrow assessment. sBCMA data available in no9 patients; FLC data available in no 16 patients. inMMyCAR

MSK Department of Medicine at ASCO 2026 Post-progression treatment analyses of evERA Breast Cancer (BC): A phase III trial giredestrant + everolimus in patients with estrogen receptor-positive, HER2-negative advanced BC previously treated with CDK4/6 inhibitor Sunday, May 31 12 p.m. CDT Komal Jhaveri, MD Breast medical oncologist & early drug development specialist Memorial Sloan Kettering Cancer Center

Key Takeaway Points/Conclusions 1. ctDNA in CRC: prognostic, not yet predictive No RCT yet shows that acting on results improves outcomes Is prognostic information enough for adoption? 2. ctDNA is a snapshot: assay, sample, and population, interpreted in evolving field. How do we harmonize across time & conditions? Pre-analytic variables: sample timing, volume, serial VS single time points Assay characteristics: sensitivity, specificity, limit of detection Clinical context: stage, prevalence, therapy, era 3. How do we do better? Novel therapies for ctDNA positive after curative therapy Every ctDNA test should generate evidence Share data and bank samples: even negative trials can be salvaged¹⁻³ 2026 ASCO PRE SENTED BY: Jonathan M. Loree, MD, FRCPC 1. RECIST: Wyatt et al, Clin Can Research 2. Friends of Cancer Research #ASCO26 ANNUAL MEETING Presentation . property of the author and ASCO. Permission required for reuse, contact permissions@asco.org (2024) 3. Reversing Early Recurence Points/Conclusions 2026. ASCO Key Takeaway Points/Conclusions ANNUAL MEETING rognostic, not yet predictive 1. ctDNA in CRC: prognostic, not yet predictive that acting on results improves outcomes No RCT yet shows that acting on results improves outcomes formation enough for adoption? Is prognostic information enough for adoption? shot: assay, sample, and population, interpreted in an 2. ctDNA is a snapshot: assay, sample, and population, interpreted in at do we harmonize across time & conditions? evolving field. How do we harmonize across time & conditions? ables: sample timing, volume, serial vs single time points Pre-analytic variables sample timing volume, serial vs single time points Assay characteristics sensitivity, specificity, limit of detection istics sensitivity, specificity, limit of detection Clinical context stage, prevalence, therapy, ora stage, prevalence, therapy, era 3. How do we do better? Novel therapies for cIDNA positive after curative therapy for ctDNA positive after curative therapy Every ctDNA test should generate evidence should generate evidence Share data and bank samples even negative trials can be salvaged1- bank samples: even negative trials can be salvaged - ASCO ASCO