lidERA Trial

[Slide 1] SAN ANTONIO BREAST CANCER SYMPOSIUM lidERA in Context of Other Adjuvant Advances UT Health AAGR I I I - Mail Come absolute HR lidERA (2.75y) lidERA (2.75y) 2.8% 0.70 ATAC (3y DFS) ATAC (3y) 2.0% 0.83 MonarchE (2y IDFS) MonarchE (2y) 2.8% 0.75 MonarchE (4y IDFS) MonarchE (4y) 6.4% 0.66 MonarchE (7y IDFS) MonarchE (7y) 6.5% 0.73 NATALEE (3y IDFS) NATALEE (3y) 2.7% 0.75 NATALEE (4y IDFS) NATALEE (4y) 4.4% 0.72 NATALEE (5y IDFS) NATALEE (5y) 4.5% 0.72 0.0% 20.0% 40.0% 60.0% 80.0% 100.0% Control Investigational Bardia A, SABCS2025; ATAC Trialists, Lancet 2005; Johnston S, ICO2020; Lancet Oncol 2023; ESMO2025; Hortobagyi G, Ann Oncol2025; Fasching PA, JAMA Oncol 2025; Crown J, resented by: Lisa A Carey, MD, ScM. ESMO2025 his presentation is the intellectual property of the presenter. Contact lisa carey@med.unc.edu for permission to reprint and/or distribute. 14

[Slide 1] CONFERENCE HIGHLIGHTS Study Patient Population Treatment / Comparator Key Findings - 10 yrs DFS ~80.1% vs 76.5% - Postmenopausal 10 yrs DFS 79% HR+/HER2+ early VS. 73.4% ALTTO breast cancer treated Adjuvant AI +/- OFS vs. SERM (eg: - Premenopausal 10 yrs DFS 90% with adjuvant tamoxifen) as endocrine therapy vs. 77.5% anti-HER2 therapy - No significant OS difference at 10 yrs - IDFS at 36mos 92.4% vs. 89.6% Stage I-III ER+, HER2- Adjuvant Giredestrant vs. lidERA - DRFI at 36mos 94.4% VS. early breast cancer Endocrine Therapy 92.1% - OS at 36mos 97% VS. 95.9% - Absolute DDFS benefit derived in HR+/HER2- early all stages at 3 years and 5 years, breast cancer (broad stage IIA-IIIC all favoring including NATALEE Update stage II-III, including Adjuvant Ribo + NSAI vs. NSAI adjuvant ribociclib NO with high risk - Maximum benefit derived in features and N+) stage IIIB and IIIC with delta of 8.9% and 6% ONC Website: X @OncBrothers www.oncbrothers.com

[Slide 1] lidERA Breast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM Distant recurrence-free interval UT Health AACR - - - - - 100 80 100 98.5% 96.1% 97:7% 94.4% 94,2% Giredestrant SOC ET 60 n 2084 n 2086 DRFI (%) 90 92.1% Events, n (%) 102 (4.9) 145 (7.0) 40 Stratified HR 0.69 80 (95% CI) (0.54, 0.89) 20 70 0 6 12 18 24 30 36 42 0 0 6 12 18 24 30 36 42 Time (months) No. at risk Giredestrant 2084 2021 1970 1931 1716 1089 344 26 SOC ET 2086 2014 1957 1897 1680 1047 325 25 Median follow-up: 32.3 months DRFI was improved vs SOC ET, with a 31% reduction in risk of developing metastatic disease Data cutoff: August 8, 2025. Median follow-up, 32.4 months in the giredestrant arm and 32.3 months in the SOC ET arm; maximum follow-up, 46.6 months and 46.3 months, respectively. CI, confidence interval; DRFI, distant recurrence-free interval; ET, endocrine therapy; HR, hazard ratio; SOC, standard-of-care. Presented by: Aditya L. Bardia, MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute. 15 --- [Slide 2] lidERA Breast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM Interim overall survival UT Health AACR - - I - - 100 80 99.5% 100 98.2% 99.4% 97.0% 97.5% Giredestrant SOC ET 60 95.9% n 2084 n 2086 os (%) Events, n (%) 57 (2.7) 71 (3.4) 90 40 Stratified HR 0.79 (95% CI) (0.56, 1.12); P = 0.1863* 20 80 0 6 12 15 24 30 36 42 0 0 6 12 18 24 30 36 42 Time (months) No. at risk Giredestrant 2084 2043 2013 1997 1887 1300 530 52 SOC ET 2086 2040 2018 1971 1852 1270 504 49 Median follow-up: 32.3 months While os data were immature, a clear positive trend was observed. OS testing will continue at future analyses Data cutoff: August 8, 2025. Median follow-up, 32.4 months in the giredestrant arm and 32.3 months in the SOC ET arm; maximum follow-up, 46.6 months and 46.3 months, respectively. At the data cutoff, the 1st OS IA was conducted (maturity 31.2% with respect to the final OS analysis). Log-rank (2-sided). p-value boundary for the 1st OS IA was 0.0001 (2-sided). Includes one death from a patient who was randomized but never dosed. Excludes one death from a patient with missing date of death. CI, confidence interval; ET, endocrine therapy; HR, hazard ratio; IA, interim analysis; OS, overall survival; SOC, standard-of-care. Presented by: Aditya L. Bardia, MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute. 16 --- [Slide 3] lidERA SAN ANTONIO Breast Cancer BREAST CANCER SYMPOSIUM® Safety overview (safety-evaluable population) UT Health AACR - - - Mass - - Giredestrant SOC ET n 2060 n 2074 Median treatment duration, months (range) 31.64 (0.03-46.36) 30.88 (0.03-46.26) Mean dose intensity, % (SD) 98.77 (3.07) 98.68 (3.73) Patients with ≥ 1 AE, n (%) AEs (all grades) 1955 (94.9) 1957 (94.4) TRAEs 1510 (73.3) 1498 (72.2) AEs with fatal outcome* 6 (0.3) 16 (0.8) TRAEs with fatal outcome 0 1 (<0.1) Grade 3-4 AEst 407 (19.8) 372 (17.9) Serious AEs 223 (10.8) 209 (10.1) AEs leading to dose interruption 261 (12.7) 136 (6.6) AEs leading to discontinuation from treatment 110 (5.3) 171 (8.2) AEs, TRAEs, Grade 3-4 AEs, and serious AEs were comparable between treatment arms Data cutoff: August 8, 2025. Giredestrant arm: Secondary cancers (colon and gastric); sepsis; gastrointestinal hemorrhage (n - 2); intestinal obstruction. SOC ET arm: Secondary cancers (pancreatic (n = 2], acute lymphocytic leukemia, bile duct, colon, gastric); sepsis (n - 1); cellulitis; endocarditis; gastrointestinal hemorrhage (n - 2); intestinal obstruction; death (n - 2); respiratory failure (n - 2); embolism; hypovolemic shock; acute myocardial infarction; hemophagocytic lymphohistiocytosis; acute kidney injury. Most common Grade 3-4 AEs were hypertension (2.6% in the giredestrant arm vs 2.0% in the SOC ET arm) and arthralgia (1.5% vs 1.8%, respectively). AE, adverse event; ET, endocrine therapy: SD, standard deviation; SOC, standard-of-care; TRAE, treatment-related adverse event. Presented by: Aditya L. Bardia, MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute. 17 --- [Slide 4] lidERA SAN ANTONIO Breast Cancer BREAST CANCER SYMPOSIUM Conclusions UT Health AACR - - Cance - Mays Cancer Conses Since approval of Als in the 2000s, lidERA Breast Cancer is the first trial to demonstrate benefit with a novel ET in early breast cancer (eBC). With a median follow-up of 32.3 months, the lidERA trial demonstrated a statistically significant and clinically meaningful improvement with upfront giredestrant over standard-of-care ET in ER+, HER2-negative, Stage I-III eBC IDFS hazard ratio: 0.70 (95% Cl: 0.57, 0.87; p = 0.0014). 3-year IDFS rates: 92.4% vs 89.6%. Overall Survival trended in favor of the giredestrant arm. DRFI was improved vs standard-of-care ET, with a 31% reduction in risk of developing distant metastatic disease. The safety profile was favorable and consistent with the known profile. The discontinuation rate was lower with giredestrant compared with standard-of-care ET. - Overall, the results support giredestrant as a potential new standard for patients with HR+/HER2- early breast cancer A/, aromatase inhibitor; CI, confidence interval; DRFI, distant recurrence-free interval; ER+, estrogen receptor-positive; ET, endocrine therapy; HR+, hormone receptor-positive; IDFS, invasive disease-free survival; OS, overall survival. resented by: Aditya L. Bardia, MD. his presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute.

[Slide 1] SAN ANTONIO lidERA Breast Cancer study design BREAST CANCER SYMPOSIUM UT Health AACR A global, randomized, open-label, multicenter Phase III trial Sen-Antonio American Association - Mays Cancer Center At least 5-year treatment duration 5-year follow-up Key eligibility criteria Participants with ER+, HER2-negative early breast cancer N = 4170 Stage I-III disease (anatomical) Giredestrant (30 mg PO QD) pN0 and pT > 1 cm with Grade 3, or Ki67 ≥ 20%, R Long-term or high score on genomic assay,* or pT4N0 1:1 follow-up Node-positive SOC ET Pre- or post-menopausalt Tamoxifen/anastrozole/letrozole/exemestane Breast cancer surgery within 12 months (Neo)adjuvant chemotherapy if indicated Stratification factors Primary endpoint Risk: Medium-1 VS high-risk$ Stage I-III breast cancer IDFS (excluding second primary non-breast cancer) Region: USA/Canada/Western Europe VS Asia-Pacific VS RoW Key secondary endpoints Previous chemotherapy: No VS yes DFS, DRFI, IDFS (including second primary non-breast invasive cancer with exception of Menopausal status: Pre-menopausal VS post-menopausal non-melanoma skin cancers and in situ carcinomas of any site), LRRFI, OS, safety Giredestrant is currently also being investigated in combination with abemaciclib in the adjuvant setting (lidERA Breast Cancer substudy 1) Enrollment August 2021 to September 2023. Up to 12 weeks of ET + CDK4/61 were allowed ER+ was defined as 2 1% positive cells by immunohistochemistry. OncotypeDx > 26 or high-risk Mammaprint T Pre-menopausal patients on aromatase inhibitors or giredestrant had to receive ovarian function suppression with an approved luteinizing hormone-releasing hormone agonist : Medium risk: pN0 and primary tumor >1 cm with high-risk biologic features (Grade 3. or Ki67 2 20% or high score on genomic assay [if available]) and pN1 with low-risk biologic features (Grade 1/2 and Ki67 < 20% and tumor 5 cm and low score on genomic assay [if available]). $ High risk: pT4, or pN2, or pN3 and pN1 with high-risk biologic features (Grade 3. or Ki67 2 20% or tumor > 5 cm, or high score on genomic assay (if available]). CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; DFS, disease-free survival; DRFI, distant recurrence-free interval; ER+, estrogen receptor-positive; ET, endocrine therapy; IDFS, invasive disease-free survival; LRRFI, locoregional recurrence-free interval; OS, overall survival; PO, orally; QD, once daily; R, randomization; RoW, rest of the world; SOC, standard-of-care ClinicalTrials. number, NCT04961996 Adapted from Geyer CE, et al. ASCO 2023 (TPS616), with permission. Presented by: Aditya L. Bardia, MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute. 7 --- [Slide 2] lidERA Breast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM® Baseline demographics and characteristics UT Health AACR Merican Association - - Recearch Mays Cancer Cerver Giredestrant SOC ET Giredestrant SOC ET n = 2084 n = 2086 n = 2084 n = 2086 Median age, years (range) 54.0 (22-91) 54.0 (25-89) ER status, n (%)+ Female sex, n (%) 2073 (99.5) 2075 (99.5) Low-positive (1-10% of cells positive) 45 (2.2) 52 (2.5) Race, n (%) Positive (> 10% of cells positive) 2030 (97.8) 2031 (97.5) AJCC stage at surgery, n (%)$ American Indian or Alaska Native 77 (3.7) 62 (3.0) I 254 (12.3) 283 (13.6) Asian 461 (22.1) 467 (22.4) II 1013 (49.0) 950 (45.7) Black or African American 50 (2.4) 50 (2.4) III 799 (38.7) 844 (40.6) Other* 263 (12.6) 232 (11.1) Nodal status, n (%) on surgical specimen White 1233 (59.2) 1275 (61.1) pN0 449 (21.6) 441 (21.2) Region, n (%) pN1 968 (46.6) 953 (45.7) Asia-Pacific pN2-3 662 (31.8) 691 (33.1) 544 (26.1) 544 (26.1) Risk, n (%) USA/Canada/Western Europe 860 (41.3) 905 (43.4) High 1448 (69.5) 1447 (69.4) Latin America/Africa/Eastern Europe 680 (32.6) 637 (30.5) Medium 636 (30.5) 639 (30.6) Menopausal status, n (%)+ Previous chemotherapy, n (%) Pre-menopausal 849 (41.0) 838 (40.4) No 396 (19.0) 450 (21.6) Post-menopausal 1220 (59.0) 1236 (59.6) Yes 1688 (81.0) 1636 (78.4) Baseline demographics and characteristics were balanced Data cutoff: August 8, 2025 "Other" refers to "multiple", "Native Hawaiian or Other Pacific Islander", "not reported", or "unknown" 1 Twenty-seven patients had unknown menopausal status (15 in the giredestrant arm and 12 in the SOC ET arm). : Twelve patients had unknown ER status (nine in the giredestrant arm and three in the SOC ET am). I One patient had Stage 0 disease (SOC ET am); 26 had unknown Stage (18 in the giredestrant arm and eight in the SOC ET arm). II Six patients had unknown nodal status (five in the giredestrant arm and one in the SOC ET arm). AJCC, American Joint Committee on Cancer; ER, estrogen receptor; ET. endocrine therapy: SOC, standard-of-care Presented by: Aditya L. Bardia MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute 10 --- [Slide 3] lidERA Breast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM Primary endpoint: IDFS UT Health AACR San.Antonio American Association - Care Mays Cancer Center 100 Giredestrant SOC ET 80 97.7% n 2084 n = 2086 100 94.6% Events, n (%) 140 (6.7) 196 (9.4) 96;9% 92.4% 60 Stratified HR 0.70 IDFS (%) 90 92:3% (95% CI) (0.57, 0.87); p = 0.0014* 89,6% 40 Exploratory analysis: IDFS by SOC ET 80 Total, Stratified HR n (95% CI) 20 AI 1745 0.73 (0.58, 0.92) 70 Tamoxifen 326 0.53 (0.35, 0.80) 0 6 12 18 24 30 36 42 0 0.3 0.8 0 6 12 18 24 30 36 42 Giredestrant better SOC ET better No. at risk Time (months) Giredestrant 2084 2021 1969 1932 1716 1088 345 26 SOC ET 2086 2016 1958 1898 1683 1048 325 25 Median follow-up: 32.3 months Statistically significant and clinically meaningful improvement in IDFS: Giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with SOC ET Data cutoff: August 8, 2025. Median follow-up, 32.4 months in the giredestrant arm and 32.3 months in the SOC ET arm; maximum follow-up, 46.6 months and 46.3 months, respectively. . Log-rank (2-sided). p-value boundary for IDFS interim analysis was 0.0217 (2-sided). AI, aromatase inhibitor, CI, confidence interval; ET. endocrine therapy. HR, hazard ratio; IDFS, invasive disease-free survival; SOC. standard-of-care Presented by: Aditya L. Bardia, MD. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucla.edu for permission to reprint and/or distribute 12 --- [Slide 4] SAN ANTONIO BREAST CANCER SYMPOSIUM® lidERA in Context of Other Adjuvant Advances UT Health AACR 1 - American Association - Cancer Received Mays Cancer Center absolute ^ HR lidERA (2.75y) lidERA (2.75y) 2.8% 0.70 ATAC (3y DFS) ATAC (3y) 2.0% 0.83 MonarchE (2y IDFS) MonarchE (2y) 2.8% 0.75 MonarchE (4y IDFS) MonarchE (4y) 6.4% 0.66 MonarchE (7y IDFS) MonarchE (7y) 6.5% 0.73 NATALEE (3y IDFS) NATALEE (3y) 2.7% 0.75 NATALEE (4y IDFS) NATALEE (4y) 4.4% 0.72 NATALEE (5y IDFS) NATALEE (5y) 4.5% 0.72 0.0% 20.0% 40.0% 60.0% 80.0% 100.0% Control Investigational Bardia A, SABCS2025; ATAC Trialists, Lancet 2005; Johnston S, JCO2020; Lancet Oncol 2023; ESMO2025; Hortobagyi G, Ann Oncol2025; Fasching PA, JAMA Oncol 2025; Crown J, Presented by: Lisa A Carey, MD, ScM. ESMO2025 This presentation is the intellectual property of the presenter. Contact lisa carey@med.unc.edu for permission to reprint and/or distribute. 14

[Slide 1] Trial Treatment Clinical/pathologic/genomic factors ET + HR+ HER2-; >4 +LNs (N2/N3) or 1-3 +LNs (N1) and G3 and/or tumor >5 CDK4/6 monarchE (Ph III) ET + abemaciclib cm (cohort 1) inhibitor 1-3 +LNs and Ki-67 >20% (G<3 and tumor <5 cm; cohort 2) NATALEE (Ph III) ET + ribociclib HR+ HER2-; stage II/III irrespective of LN status; high risk for stage IIA T2N0 disease (G2 and Ki-67 >20% or high genomic risk; G3) PARPi OlympiA (Ph III) Olaparib HR+ HER2- or TNC gBRCA1/2m and high-risk factors Oral Giredestrant mono Medium-/high-risk stage I-III HR+, HER2- BC based on anatomic (tumor lidERA (Ph III) SERDS abemaciclib substudy size, nodal status) and biologic features (grade, Ki67 ,OncotypeDx or + MammaPrint) CAMBRIA-2 (Ph III) Camizestrant + abemaciclib Intermediate-high to high-risk HR+, HER2- Risk defined by specified clinical and biologic criteria Oral CAMBRIA-1 (Ph III) Camizestrant HR+ HER2- intermediate or high risk based on clinical-pathological risk features SERDS ELEGANT (Ph III) Elacestrant HR+ HER2- N+ with high risk at initial screening (After 2-5 years of ET (+/- CDK4/i) EMBER-4 (Ph III) Imlunestrant HR+ HER2- increased risk based on clinical-pathological risk

[Slide 1] lidERA Breast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM® Distant recurrence-free interval UT Health AAGR A Market - I - Mays General Canada 100 80 100 98.5% 96.1% 97.7% 94.4% 60 94,2% Giredestrant SOC ET DRFI (%) 90 92.1% n= 2084 n = 2086 Events, n (%) 102 (4.9) 145 (7.0) 40 Stratified HR 80 0.69 (95% CI) (0.54, 0.89) 20 70 0 6 0 12 18 24 30 36 42 0 6 12 18 24 30 36 42 No. at risk Time (months) Giredestrant 2084 2021 1970 1931 SOC ET 2086 1716 1089 2014 344 1957 26 1897 1680 1047 325 25 Median follow-up: 32.3 months DRFI was improved vs SOC ET, with a 31% reduction in risk of developing metastatic disease Presented by: Aditya L. Bardia, MD. CI, Data confidence cutoff: August interval; 8, 2025. DRFI, Median distant follow-up, recurrence-free 32.4 months interval; in ET, the endocrine giredestrant therapy; arm and HR, 32.3 hazard months ratio; in the SOC, SOC standard-of-care. ET arm; maximum follow-up, 46.6 months and 46.3 months, respectively. This presentation is the intellectual property of the presenter. Contact ABardia@mednet.ucfa.edu for permission to reprint and/or distribute. 15 UNC LINEBERGER COMPREHENSIVE