PROTEUS Trial

2026 ASCO ANNUAL MEETING Perioperative (Neoadjuvant and Adjuvant) Apalutamide + ADT vs Placebo + ADT With Radical Prostatectomy in High-Risk Localized or Locally Advanced Prostate 2026 ASC ANNUAL MEETI Cancer: Final Analysis of the PROTEUS Phase 3 Study Mary-Ellen Taplin1, Martin Gleave², Neal D Shore³, Angela Lopez⁴, Alexander Kretschmer⁵, Eleni Efstathiou®, Ronaldo Damião⁷, Toshiyuki Kamoto®, Ashley Ross®, Alberto Briganti10, Boris A Hadaschik11, Axel Heidenreich12, Alvaro Juarez Soto13, Brendan Rooney14, Shaozhou Ken Tian⁵, Lisa Wetherhold5, Branko Miladinovic15, Sharon McCarthy5, Christopher P Evans16, Adam S Kibel17 Lank Center for Destroutery Cologe Institute, Beston, MA USA Department of of C, Myttle Beach, SC, Johnson Admin, LOS Angeles, CA, I 1. I House, PA, I 8 Re L of Consortium Case, High Nycombe, UK Diego, CA USA, Remove NV, MA, 2026 ASCO #ASCO26 Mary Elien Tapin MO, FASCO ASCO ANNUAL MEETING - CONSULTS Perioperative (Neoadjuvant and Adjuvant) Apalutamide ADT vs Placebo + ADT With Radical Prostatectomy in High-Risk Localized or Locally Advanced Prostate Cancer: Final Analysis of the PROTEUS Phase 3 Study 0 ASCO --- PROTEUS: A Randomized, Double-Blind, Placebo- Controlled Phase 3 Study in HR-LPC Post N=2109 Neoadjuvant Adjuvant treatment (C1 through C6) (C7 through C12) M A R D N D Z E I 2 4 APA wks wks APA (240 mg QD) (240 mg QD) + ADT + ADT PSMA-PET (3 months after EOT) Patients With RPª PSA every 3 months 2026ASCO HR-LPC + Conventional and PSMA-PET ADT ANNUAL MEETING Imaging at BCF (PSA >0.2 ng/mL); PBO + ADT PBO + ADT every 6 months thereafter 1:1 Stratification: Adjuvant or salvage RT cN0 vs N1 post-RP at investigator's Gleason score (7 vs 8-10) discretion Region (North America, Europe, ROW) To complement these data, a substudy is ongoing to further inform on the role of APA + ADT + RP versus RP alone Patients randomized from July 15, 2019, to June 30, 2022. Protocol Amendment 7 for including PSMA-PET into MFS assessment (April 14, 2022). APA, apalutamide; BCF, biochemical failure; C, cycle; EOT, end of treatment; PBO, placebo; PSA, prostate-specific antigen; PSMA-PET, prostate-specific membrane antigen positron emission tomography, QD, daily; ROW, rest of the world; RT, radiation therapy. APA/PBO is stopped 2 weeks prior to planned RP and then resumed 4 weeks after RP. Cardiovascular risk prophylaxis and venous thromboembolism prophylaxis given based on risk, 2026 ASCO #ASCO26 PRE SENTED BY: Mary-Ellen Taplin, MD, FASCO ASCO - SECETY OF I ANNUAL MEETING the registration KNOWLEDGE CONQUERS CANCER - --- PRIMARY END POINT Dual Primary End Point Met: MFS by Conventional or PSMA-PET Imaging 100 APA + ADT 20% reduction in the 80 risk of metastasis or MFS (%) Assessed by BICR PBO + ADT death after 1 year 60 of perioperative APA + ADT with RP by BICR 2026ASCO 40 ANNUAL MEETING 20 HR, 0.80a 95% CI, 0.67-0.96 Investigator-assessed p=0.02b MFS was consistent: 0 0 12 24 36 48 60 72 84 HR, 0.74; No. at risk Months Since Randomization 95% Cl, 0.62-0.87; APA + ADT 1057 992 922 837 659 382 62 0 p=0.0004 PBO + ADT 1052 1000 924 812 634 385 61 0 MFS: Time to first occurrence of radiographic distant metastasis based on conventional imaging or PSMA-PET imaging, pathologic finding of distant metastasis, or death from any cause Hazard ratio (HR) is from stratified proportional hazards model HR <1 favors APA ADT. P Value is from a log-rank test stratified by Gleason score (7, 28), nodal status (NO, N1), geographic region (North America, Europe, and rest of the world). 2026 ASCO PRESENTED en Mary-Ellen Taplin, MD, FASCO ASCO #ASCO26 ANNUAL MEETING KNOWLEDGE CONDUERS CANCER I the - --- Conclusions PROTEUS sets a new standard of care in HR-LPC Unprecedented Enhanced Disease Known Safety More to Come Study Design Control of RP Profile 2026ASCO Significant benefit: Substudy comparing ANNUAL MEETING 9x greater pCR/MRD with direct RP Largest size to date 20% less risk of MFS Tolerability of Biomarker Novel end points 29% less risk of APA+ADT consistent assessment PSMA-PET inclusion recurrence or death with prior studies Surgical outcomes 3 years longer time Pathology correlates to next treatment 2026 ASCO #ASCO26 PRESENTED am Mary-Ellen Taplin, MD, FASCO ASCO - - INCOLOGY ANNUAL MEETING Presentation - of - euthor and ASCO - - for - contact - KNOWLEDGE CONQUERS CANCER

Dual Primary End Point Met: pCR/MRD PRIMARY END POINT 12 8.9% 9-fold improvement in 10 OR, 10.17 pCR/MRD at RP after pCR/MRD (%) by Pathology-BICR 95% CI, 5.27-19.64 6-cycle neoadjuvant 8 p<0.0001a APA + ADT vs PBO + ADT 6 Exploratory end point of RCB 4 (SypT2, NO, ≤0.25 cm3) 5.1% ypTo corroborates pCR/MRD: 2 1.0% APA + ADT vs PBO + ADT, T 30.6% vs 11.7% 0 0.4% Урто APA + ADT OR, 3.36; PBO + ADT 94/1057 10/1052 95% CI, 2.67-4.23; p<0.0001 pCR/MRD: Minimal residual tumor ≤5 mm (greatest dimension of largest tumor lesion) in prostate-confined disease (sypT2, NO) or no tumor identified (ypTo) RCB: Residual cancer burden ≤0.25 cm3 in prostate-confined disease (sypT2, NO) Error bars indicate 95% confidence intervals (Cls). Odds ratio (OR) is from a logistic regression adjusted for stratification factor, OR favors APA + ADT. P Value is based on Cochran-Mantel-Haenszel test stratified by Gleason score (7, ≥8), nodal status (ND, N1), geographic region (North America, Europe, and rest of the world). 2026 ASCO #ASCO26 PRESENTED BY: Mary-Ellen Taplin, MD, FASCO ASCO - GREA - ANNUAL MEETING Presentation is property of to author and ASCO Permission required by INSI, contact KNOWLEDGE CONDUERS CANCER

PROTEUS: A Randomized, Double-Blind, Placebo- Controlled Phase 3 Study in HR-LPC Post N=2109 Neoadjuvant Adjuvant treatment (C1 through C6) (C7 through C12) M A O N R D D Z E I 2 4 APA wks wks APA (240 mg QD) (240 mg QD) + ADT RPª + ADT PSMA-PET (3 months after EOT) Patients With PSA every 3 months HR-LPC + Conventional and PSMA-PET ADT imaging at BCF (PSA >0.2 ng/mL); PBO + ADT PBO + ADT every 6 months thereafter 1:1 Stratification: Adjuvant or salvage RT cN0 vs N1 post-RP at investigator's Gleason score (7 vs 8-10) discretion Region (North America, Europe, ROW) To complement these data, a substudy is ongoing to further inform on the role of APA + ADT + RP versus RP alone Patients randomized from July 15, 2019, to June 30, 2022. Protocol Amendment 7 for including PSMA-PET into MFS assessment (April 14, 2022). APA, apalutamide; BCF, biochemical failure; C, cycle; EOT, end of treatment; PBO, placebo; PSA, prostate-specific antigen; PSMA-PET, prostate-specific membrane antigen positron emission tomography; QD, daily; ROW, rest of the world; RT, radiation therapy. *APA/PBO is stopped 2 weeks prior to planned RP and then resumed 4 weeks after RP. Cardiovascular risk prophylaxis and venous thromboembolism prophylaxis given based on risk. 2026 ASCO #ASCO26 PRESENTED BY: Mary-Ellen Taplin, MD, FASCO ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- KEY SECONDARY END POINT Event-Free Survival 100 29% reduction in the 80 APA + ADT risk of oncologic event Event-Free Survival (%) 57.1 months or death 60 40 38.4 months 20 HR, 0.71 PBO + ADT 95% CI, 0.63-0.80ᵃ p<0.0001b 0 0 12 24 36 48 60 72 84 No. at risk Months Since Randomization APA + ADT 1057 988 788 625 452 246 45 0 PBO + ADT 1052 952 699 522 382 223 48 0 EFS: Time to first of BCF (PSA progression) or local or regional recurrences or distant metastasis, or death by any cause "HR is from stratified proportional hazards model; HR <1 favors APA . ADT. to Value is from a log-rank test stratified by Gleason score (7, 28), nodal status (NO, N1), geographic region (North America, Europe, and rest of the world). 2026 ASCO #ASCO26 PRS SENTED - Mary-Ellen Taplin, MD, FASCO ASCO FUERCIAN OF CURRICAL - ANNUAL MEETING Presentation a property of the - and ASCO Permission required for - contact KNOWLEDGE CONQUERS CANCER --- SECONDARY END POINT Frequency of Treatment-Related Adverse Events APA + ADT PBO + ADT Safety Population, n (%) (n=1050) (n=1050) All grades Treatment-related AE 1000 (95.2) 985 (93.8) Treatment-related AEs 289 (27.5) 198 (18.9) Grade 3/4 Treatment-related AEs leading to dose reduction 118 (11.2) 24 (2.3) Treatment-related AEs leading to dose interruption® 126 (12.0) 46 (4.4) All grades Treatment-related AEs leading to deathᵇ 7 (0.7) 1 (0.1) AC, adverse event. Treatment-related AEs are those that occurred on or after the first dose of study drug through the last dose of study treatment . 30 days or prior to the start of subsequent therapy, whichever is earlier, or any AR that is considered treatment related regardless of the start date of the event. An AE is categorized as related If assessed by the Investigator as possibly, probably, or very likely related to study drug (apalutamide or placebo), ADT, or RP. AES leading to treatment interruption or dose reduction are based on AE action taken. Pincludes grade 5 events; AEs leading to death are based on AS outcome of tatal. 2026 ASCO #ASCO26 PRI SENTED - Mary-Ellen Taplin, MD. FASCO ASCO - OF CERTICAL ANNUAL MEETING Presentation - property of the author and ASCO Permission required - - - KNOWLEDGE CONQUERS CANCER --- Conclusions PROTEUS sets a new standard of care in HR-LPC Unprecedented Enhanced Disease Known Safety More to Come Study Design Control of RP Profile Significant benefit: Substudy comparing 9x greater pCR/MRD with direct RP Largest size to date 20% less risk of MFS Tolerability of Biomarker Novel end points APA+ADT consistent 29% less risk of assessment PSMA-PET inclusion recurrence or death with prior studies Surgical outcomes 3 years longer time Pathology correlates to next treatment 2026 ASCO #ASCO26 PRI SENTED BY Mary-Ellen Taplin, MD. FASCO ASCO **** - SOCIETY or CURRICAL - ANNUAL MEETING I a 1 I person . I I . I KNOWLEDGE CONQUERS CANCER

High-risk MO prostate cancer: two intensification paths PROTEUS vs STAMPEDE: informative, not head-to-head PROTEUS STAMPEDE Aspect Apalutamide + RP Abiraterone + RT Local therapy Radical prostatectomy Prostate ± pelvic radiotherapy ARPI & duration Apalutamide Abiraterone (± enzalutamide) ~12 months perioperative for 2 years Population High-risk localized / locally advanced High-risk MO surgery candidates often N+ or very high PSA/T-stage/Gleason MFS benefit 5-year: 78.2% vs 73.5% 6-year: 82% VS 69% ~4.7% absolute ~13% absolute; HR 0.53 os immature / not highlighted Clear OS benefit os benefit EFS and delayed therapy improved HR 0.60; ~9-10% absolute at 6 years Other key win Major pathological response Strong gains in PCa-specific survival 8.9% vs 1.0% and PFS Toxicity More grade 3-4 AEs More grade 3-4 AEs mainly rash acceptable in context Clinical take-home Both trials support AR pathway intensification with definitive local therapy. The key question is not which trial wins, but which path best fits which patient. Not a head-to-head comparison: differences in design, risk, local therapy, drug duration, and follow-up limit direct comparison.