Slide 1: Unlocking the Potential of Treating Cancers That Involve the PAM Pathway
Unlocking the Potential of Treating Cancers That Involve the PI3K/AKT/mTOR (PAM) Pathway August 2026
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains statements that constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements relating to the potential therapeutic benefits of gedatolisib; the size, design and timing of
Slide 3: REVTORPYK Is Now FDA-Approved
REVTORPYK Is Now FDA-Approved REVTORPYK is indicated in combination with fulvestrant, with or without palbociclib, for the treatment of HR+/HER2- locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after ≥ 1 line of endocrine therapy in the met
Slide 4: Overview of REVTORPYK U.S. Prescribing Information
Overview of REVTORPYK U.S. Prescribing Information INDICATION: REVTORPYK is indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with HR+/HER2- locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progressi
Slide 5: REVTORPYK has a $10B+ U.S. market potential in 1L and 2L HR+/HER2- ABC
REVTORPYK has a $10B+ U.S. market potential in 1L and 2L HR+/HER2- ABC With cash, cash equivalents and short-term investments of $754M, expect funding to take us through 2029 LARGEST TWO POSITIVE UNTAPPED DRUG BEST-IN-CLASS, PHASE 3 DEVELOPMENT FIRST-IN-CLASS READOUTS IN 2L+ OPPORTUNITY PAM INHIBITO
Slide 6: The PAM Pathway is the Most Underdeveloped Target in Solid Tumors
The PAM Pathway is the Most Underdeveloped Target in Solid Tumors PAM is the most frequently altered PAM revenue potential comparable pathway in solid tumors to CDK4/6 & AR therapies $12.4B $10.1B altered pathways1 38% % Tumors w / Peak Global Revenues2 8% 5% 4% $1B Target PAM HER2 EGFR ALK Target P
Slide 7: Multiple potential blockbuster indications in both tumor types
Multiple potential blockbuster indications in both tumor types HR+/HER2- Breast Cancer Advanced Prostate Cancer US 156,880 EU5+J 125,080 116,600 101,760 82,880 Patient Population 93,280 Addressable 78,440 66,080 69,960 61,600 53,760 49,280 53,000 41,440 36,960 28,000 74,000 59,000 55,000 48,000 37,0
Slide 8: Positioning REVTORPYK for strong market adoption in PIK3CA Wild-Type & Mutant breast cancer
Positioning REVTORPYK for strong market adoption in PIK3CA Wild- Type & Mutant breast cancer LARGE SIGNIFICANT UNMET WELL COMPELLING VALUE POPULATION NEED IN HR+/HER2- DIFFERENTIATED PROPOSITION ADVANCED BREAST 37,000 patients with Gedatolisib MOA, Best-in-class efficacy + safety HR+/HER2- ABC recei
Slide 9: Fragmented market with no "Go To" option for PIK3CA Wild-Type HR+HER2- ABC patients
Fragmented market with no “Go To” option for PIK3CA Wild-Type HR+HER2- ABC patients after progressing on initial endocrine therapy Current Treatments Used in 2L PIK3CA Wild Type ABC Other Other Chemo-Based Regimen CDK4/6i + ET Xeloda (capecitabine) Endocrine Mono HER2 ADC mTORC1 Oral SERD Source: Ce
Slide 10: Co-Primary Endpoint: PFS of REVTORPYK Triplet vs. Fulvestrant
Co-Primary Endpoint: PFS of REVTORPYK Triplet vs. Fulvestrant 7.3 months improvement in mPFS 100 Geda + Palbo + 90 >4.5x mPFS fulvestrant Fulvestrant with REVTORPYK triplet vs fulvestrant alone (n=131) 80 (n=131) Progression-free Survival (%) 70 Median PFS, 9.3 2.0 months (95% CI) (7.2-16.6) (1.8-2.
Slide 11: Co-Primary Endpoint: PFS of REVTORPYK Doublet vs. Fulvestrant
Co-Primary Endpoint: PFS of REVTORPYK Doublet vs. Fulvestrant 5.4 months improvement in mPFS 100 90 >3.5x mPFS Geda + fulvestrant Fulvestrant with REVTORPYK triplet vs fulvestrant alone (n=130) (n=131) 80 Progression-free Survival (%) 70 Median PFS, 7.4 2.0 months (95% CI) (5.5-9.9) (1.8-2.3) 60 50
Slide 12: How Do the REVTORPYK Regimens Fit in the 2L Landscape?
How Do the REVTORPYK Regimens Fit in the 2L Landscape? Hazard ratios for regimens compared to endocrine monotherapy as primary endpoint in a Phase 3 trial PATIENT HAZARD RATIO (LOWER IS BETTER) POPULATION 2ND LINE HR+/HER2-/PIK3CA WILD-TYPE ABC REVTORPYK + PIK3CA WT 0.24 Fulv + Palbo1 PIK3CA WT REVT
Slide 13: How Do the REVTORPYK Regimens Fit in the 2L Landscape?
How Do the REVTORPYK Regimens Fit in the 2L Landscape? Gedatolisib regimens showed highest multiple of mPFS improvement versus endocrine therapy PATIENT MULTIPLE OF mPFS IMPROVEMENT IN MONTHS RELATIVE TO ENDOCRINE MONOTHERAPY POPULATION PIK3CA WT REVTORPYK + Fulvestrant + Palbociclib1 4.7X PIK3CA WT
Slide 14: Entering Launch with Market and Organizational Momentum
Entering Launch with Market and Organizational Momentum ENGAGED KEY PAM PATHWAY & LAUNCH PLAN EXPERIENCED & STAKEHOLDERS REVTORPYK TACTICS IN PLACE TRAINED TEAMS AWARENESS/ DEPLOYED & READY • >1,500 KOLs & Community ADVOCACY • Promotional Materials & TO DELIVER Breast Cancer Experts Programs • Over
Slide 15: Access for REVTORPYK is Designed to Offer Rapid Access with Seamless Support Solutions
Access for REVTORPYK is Designed to Offer Patients and Providers Rapid Access with Seamless Support Solutions of top Payer Pathways Comprehensive & Simple Patient Support 100% were engaged pre-approval 100% of top 36 Strategic Accounts were engaged pre-approval Digital Enrollment of US medical benef
Slide 16: REVTORPYK Launch Priorities
REVTORPYK Launch Priorities DRIVE AWARENESS RAPID ADOPTION DELIVER ACCESS Rapid engagement of core Unique MOA, Strong Efficacy, Broad payer coverage and REVTORPYK customers Tolerable AE profile world-class patient services 9,000+ 88 1 Academic and Community HCPs Oncology Sales Specialists Aligned Te
Slide 17: Gedatolisib Clinical Development Programs
Gedatolisib Clinical Development Programs 17
Slide 18: Difficult to Safely and Comprehensively Inhibit the PAM Pathway
Difficult to Safely and Comprehensively Inhibit the PAM Pathway Optimal efficacy may require inhibition of all Class I PI3K isoforms and mTORC1 and mTORC2 MULTIPLE PATHWAY TARGETS THERAPEUTIC WINDOW FOR ORAL PROVIDE FUNCTIONAL REDUNDANCY PI3K/mTOR INHIBITORS IS NARROW If only a single target is inhi
Slide 19: Gedatolisib Has a Highly Differentiated Mechanism of Action and Potency
Gedatolisib Has a Highly Differentiated Mechanism of Action and Potency Potential First-in-Class PAM Inhibitor with superior cytotoxicity vs. single target PAM inhibitors Cell-Free Biochemical Dose Response Analysis Live Cell Proliferation Rate Dose Response Analysis7 IC50 (nM)1 Average values for 1
Slide 20: Clinical Development Programs: Current
Clinical Development Programs: Current 2ND LINE 2ND LINE 1ST LINE METASTATIC HR+/HER2- HR+/HER2- CASTRATION ADVANCED ADVANCED RESISTANT BREAST CANCER BREAST CANCER PROSTATE CANCER Phase 3 clinical trial for Phase 3 clinical trial for Phase 1b/2 clinical trial for gedatolisib with fulvestrant gedatol
Slide 21: Phase 3 VIKTORIA-1 2nd Line HR+, HER2- ABC
Phase 3 VIKTORIA-1 2nd Line HR+, HER2- ABC 21
Slide 22: HR+/HER2- Breast Cancer Treatment Landscape
HR+/HER2- Breast Cancer Treatment Landscape1 ~30,000 women in US and ~33,000 women in 5EU and Japan die from breast cancer annually2 DISEASE STAGE ADVANCED AND METASTATIC STAGE LOCALIZED AND REGIONAL STAGE I-III III (INOPERABLE) OR STAGE IV Low Higher ~32% 1st line 2nd line 3rd line 4th line recurre
Slide 23: VIKTORIA-1 PIK3CA Mutant Cohort
VIKTORIA-1 PIK3CA Mutant Cohort 23
Slide 24: Clinical Strategy: Simultaneous Blockade of PAM, ER, & CDK4/6 Pathways
Clinical Strategy: Simultaneous Blockade of PAM, ER, & CDK4/6 Pathways CLINICAL HYPOTHESIS Blockade of interdependent ER, PI3K, mTOR & CDK signaling pathways is required to optimize anti-tumor control PAM inhibition:1-4 Blockades PAM pathway and limits cross- activation when ER or CDK4/6 is inhibi
Slide 25: VIKTORIA-1 Study 2 (PIK3CA MT): Phase 3 Clinical Trial of Gedatolisib
VIKTORIA-1 Study 2 (PIK3CA MT): Phase 3 Clinical Trial of Gedatolisib HR+/HER2- ADVANCED BREAST CANCER Arm D PRIMARY Gedatolisib | 180mg IV once weekly, 3 weeks on, 1 week off ENDPOINTS Eligibility Criteria: Palbociclib | 125mg daily, 21 days on, 7 days off PFS (BICR) Pre- & postmenopausal women
Slide 26: Patient Population Includes Significant Proportion with Aggressive Disease
Patient Population Includes Significant Proportion with Aggressive Disease 76% with liver or lung metastases and endocrine therapy resistant patients included Gedatolisib + Gedatolisib + palbociclib+ Gedatolisib + Alpelisib + palbociclib+ Gedatolisib + Alpelisib + fulvestrant fulvestrant Fulvestrant
Slide 27: Primary & Secondary Endpoints Met: mPFS Doubled Relative to Control
Primary & Secondary Endpoints Met: mPFS Doubled Relative to Control Gedatolisib triplet and gedatolisib doublet vs. alpelisib + fulvestrant, BICR assessment 100 Geda + palbo + Alpelisib + 100 Geda + Alpelisib + fulvestrant fulvestrant fulvestrant fulvestrant 90 (n=155) (n=155) 90 (n=52) (n=155) Medi
Slide 28: PFS in Key Subgroups: Gedatolisib Triplet vs. Alpelisib + Fulvestrant
PFS in Key Subgroups: Gedatolisib Triplet vs. Alpelisib + Fulvestrant Gedatolisib + Palbociclib + Fulvestrant Alpelisib + Fulvestrant Subgroup n/N n/N Hazard Ratio (95% CI) Age <65 years 53/107 65/97 0.47 (0.32-0.68) ≥65 years 15/48 34/58 0.46 (0.25-0.87) Menopause status Pre/perimenopause 12/25 20/
Slide 29: PFS in Key Subgroups: Gedatolisib Doublet vs. Alpelisib + Fulvestrant
PFS in Key Subgroups: Gedatolisib Doublet vs. Alpelisib + Fulvestrant Gedatolisib + Fulvestrant Alpelisib + Fulvestrant Subgroup n/N n/N Hazard Ratio (95% CI) Age <65 years 14/27 65/97 0.51 (0.28-0.88) ≥65 years 11/25 34/58 0.63 (0.32-1.31) Menopause status Pre/perimenopause 2/6 20/29 0.26 (0.07-1.1
Slide 30: Key Secondary Endpoint: Overall Survival (Interim Analysis)
Key Secondary Endpoint: Overall Survival (Interim Analysis) Favorable OS trend for both gedatolisib-triplet and gedatolisib-doublet 100 100 90 90 80 80 70 70 Overall Survival (%) Overall Survival (%) 60 60 50 50 40 40 30 30 Geda + Alpelisib + Geda + palbo + Alpelisib + fulvestrant fulvestrant fulves
Slide 31: Secondary Endpoint: Tumor Response by BICR
Secondary Endpoint: Tumor Response by BICR Gedatolisib-triplet 49% ORR is highest reported in a Phase 3 study w/endocrine regimen in 2L Geda + Palbo + Fulvestrant Gedatolisib + Fulvestrant Alpelisib + Fulvestrant Endpoint, % (n=133) (n=42) (n=127) Best Overall Response Complete response 0 0 0.8 Part
Slide 32: Duration of Response
Duration of Response Gedatolisib-triplet and gedatolisib-doublet mDoR was 2x and 3x alpelisib + fulvestrant mDoR, respectively Geda + palbo + Alpelisib + Geda + Alpelisib + fulvestrant fulvestrant fulvestrant fulvestrant (n=65) (n=33) (n=15) (n=33) 100 100 mDOR, 15.7 7.5 mDOR, 24.2 7.5 90 months (95
Slide 33: Gedatolisib Regimens Were Generally Well-Tolerated, With Low Discontinuation Rates
Gedatolisib Regimens Were Generally Well-Tolerated, With Low Discontinuation Rates; Majority of TRAE’s Grade 1/2; Low Hyperglycemia and Diarrhea Rates Gedatolisib + palbociclib + fulvestrant Gedatolisib + fulvestrant Alpelisib + fulvestrant Exposure (n=153) (n=52) (n=152) Median RDI, Geda (IQR) 93.3
Slide 34: How Does the Gedatolisib Regimen Potentially Fit in the 2L Landscape?
How Does the Gedatolisib Regimen Potentially Fit in the 2L Landscape? Gedatolisib regimens induced the highest mPFS ever reported in 2L HR+/HER2- ABC PATIENT 2ND LINE ER+/HER2-/PIK3CA MUTANT ABC POPULATION PIK3CA mPFS 11.3 months MT Gedatolisib + Fulvestrant 1 ORR 36% PIK3CA mPFS 11.1 months MT Geda
Slide 35: 1st Line HR+, HER2- ABC
1st Line HR+, HER2- ABC 35
Slide 36: VIKTORIA-2 Phase 3 Trial Design for 1st-Line HR+/HER2- ABC
VIKTORIA-2 Phase 3 Trial Design for 1st-Line HR+/HER2- ABC Arm A Primary Endpoint: Eligibility Criteria: Gedatolisib: 180 mg IV once weekly; 3 weeks on, 1 week off PFS (BICR): Pre- & postmenopausal women & men Palbociclib: 125 mg daily; 21 days on, 7 days off Arm A vs. Arm B No prior therapy f
Slide 37: Phase 1B: Gedatolisib + Palbociclib + Letrozole in ES 1L HR+/HER2- ABC
Phase 1B: Gedatolisib + Palbociclib + Letrozole in ES 1L HR+/HER2- ABC mPFS of 48.6 months, mDOR of 46.9 months, and ORR of 79% Treatment-Naïve Patients who are Endocrine Sensitive (ES) (N=41) Escalation Arm A Expansion Arm A Total Treatment Naïve Progression-Free Survival n = 11 n = 30 n = 41 (full
Slide 38: Phase 1B: Gedatolisib + Palbociclib + Letrozole in 1L HR+/HER2- ABC (N=41)
Phase 1B: Gedatolisib + Palbociclib + Letrozole in 1L HR+/HER2- ABC (N=41)1 mPFS and ORR for treatment-naïve ES patients compares favorably to published data for SOC palbociclib + letrozole2 Median Progression Free Survival Tumor Size Change 48.6 Months ORR = 79% (26/33) 100 90 80 Progression Free S
Slide 39: Phase 1B: Overall Survival in 1L HR+/HER2- ABC (N=41)
Phase 1B: Gedatolisib + Palbociclib + Letrozole in 1L HR+/HER2- ABC (N=41)1 mOS data for treatment-naïve patients ETS compares favorably to published data for current SOC Median Overall Survival 77.3 Months Overall survival (%) RELEVANT OS DATA IN 1L SETTING Palbociclib + letrozole: 53.8 months2
Slide 40: Gedatolisib Combo vs. SOC for 1L HR+ / HER2- ABC (Endocrine Sensitive)
Gedatolisib Combo vs. SOC for 1L HR+ / HER2- ABC (Endocrine Sensitive) Gedatolisib Combo Offers Potential for Superior mPFS Compared to 1L SOC 1ST LINE HR+/HER2- ABC mPFS 48.6 months Gedatolisib + Palbociclib + Letrozole1 ORR 79% mPFS 24.8 Months Palbociclib + Letrozole2 ORR 55% mPFS 14.5 mos Letroz
Slide 41: Relevant Comparisons to VIKTORIA-2 Controls
Relevant Comparisons to VIKTORIA-2 Controls B2151009 study results for 1L patients compares favorably to published data for 1L ETS patients Gedatolisib + Palbociclib + Letrozole Ribociclib + Letrozole Palbociclib + Fulvestrant 1 2 N=41 N=441 N=164 3 WT / MT WT/ MT MT PIK3CA Status (76% / 22%) (67% /
Slide 42: Gedatolisib for Prostate Cancer
Gedatolisib for Prostate Cancer 42
Slide 43: Androgen Signaling is the Key Driver of Prostate Cancer
Androgen Signaling is the Key Driver of Prostate Cancer The PI3K/AKT/mTOR (PAM) pathway helps promote excessive cell proliferation and resistance to apoptosis THE AR PATHWAY IS THE THE PAM PATHWAY PLAYS A KEY PRIMARY THERAPEUTIC TARGET ROLE IN mCRPC The androgen receptor (AR) drives the AR and P
Slide 44: Prostate Cancer Disease and Treatment Landscape
Prostate Cancer Disease and Treatment Landscape1,2 34,700 men in US and 62,400 men in 5EU and Japan die from prostate cancer annually3,4 DISEASE STAGE nmCRPC Non-metastatic castration resistant Localized Systemic Rising PSA mCRPC mCRPC Biochemical or tumor prostate cancer progression 1L 2L recurrenc
Slide 45: Limited Benefit from Current Therapeutic Options for 2L mCRPC Patients
Limited Benefit from Current Therapeutic Options for 2L mCRPC Patients After Treatment with AR Inhibitor Significant need for better therapeutic options 1st Line Treatment Outcomes 2nd Line Treatment Outcomes (post AR inhibitor treatment) 20.0 16.5 mPFS (mo) 6.7 5.6 5.6 5.5 Drugs Xtandi1 Zytiga2 Doc
Slide 46: Combining a PAM Inhibitor with an AR Inhibitor has Strong Scientific Rationale
Combining a PAM Inhibitor with an AR Inhibitor has Strong Scientific Rationale Biological parallels between mCRPC and HR+ ABC – PAM and hormonal pathway drive progression 1,2,3 PI3K/AKT/mTOR + AR Inhibition Treatment Rationale Favorable clinical data in mCRPC with PAM inhibitors provides “proof-of
Slide 47: CELC-G-201: Phase 1b/2 Trial Design Overview
CELC-G-201: Phase 1b/2 Trial Design Overview Evaluating gedatolisib plus darolutamide to determine preliminary safety and efficacyRP2D DOSE ESCALATION DOSE EXPANSION Determine RP2D, assess safety and tolerability Primary endpoint: rPFS6 Arm 1 Cohort A Gedatolisib + 120mg + darolutamide Gedatolisib +
Slide 48: CELC-G-201: Gedatolisib + Darolutamide for Arms 1 and 2
CELC-G-201: Gedatolisib + Darolutamide for Arms 1 and 2 rPFS6 for G + ARi (darolutamide) compares favorably to historical data for ARi monotherapy TREATMENT CELC-G-201 6-MONTH rPFS PROBABILITY Arms 1 & 2 (N=38) REGIMEN (TRIAL) rPFS6 67% Gedatolisib + ARi 67% (CELC-G-201)1 Median rPFS 9.1 months Disc
Slide 49: Key Milestones Achieved and Upcoming in 2026-2027
Key Milestones Achieved and Upcoming in 2026-2027 VIKTORIA-1 WT data VIKTORIA-1 MT data NCCN Guidelines VIKTORIA-1 MT data Present additional VIKTORIA-1 published in JCO presented at ASCO submission sNDA submission mutant and wild-type data at upcoming medical conferences Update on Phase 1B mCRPC st
Slide 50: REVTORPYK has a $10B+ U.S. market potential in 1L and 2L HR+/HER2- ABC
REVTORPYK has a $10B+ U.S. market potential in 1L and 2L HR+/HER2- ABC With cash, cash equivalents and short-term investments of $754M, we are funded through 2029 LARGEST TWO POSITIVE UNTAPPED DRUG BEST-IN-CLASS, PHASE 3 DEVELOPMENT FIRST-IN-CLASS READOUTS IN 2L+ OPPORTUNITY PAM INHIBITOR ABC SETTIN
Slide 51: Additional Data
celcuity Additional Data
Slide 52: Gedatolisib + Trastuzumab Biosimilar in 3L+ HER2+ ABC Patients (N=44)
Gedatolisib + Trastuzumab Biosimilar in 3L+ HER2+ ABC Patients (N=44) 43% objective response rate Best Response Duration of Response 2 of 44 best response was a complete response (CR) 17 of 44 best response was a partial response (PR) Source: Kim ASCO 2025. Note: Data presented is as of a cutoff
Slide 53: Gedatolisib + Paclitaxel + Carboplatin in Patients with Solid Tumors (N=17)
Gedatolisib + Paclitaxel + Carboplatin in Patients with Solid Tumors (N=17)1 65% ORR in all patients, 82% ORR in patients with ovarian cancer Ovarian Cancer (N=11) | ORR: 82% Clear cell ovarian cancer (CCOC) (N = 10) ‒ ORR: 80% - 5/10 PR, 3/10 CR Low grade serous ovarian (N=1) ‒ 1/1 PR Other sol
Slide 54: Key Gedatolisib Patents
Key Gedatolisib Patents Loss of exclusivity now expected to occur in 2042; anticipate new formulations to extend this period further Subject Matter Patent Expiration Date Note Composition of matter (API) Includes 209 days of patent term adjustment (PTA), and expected 5 Dec 2034 (generic and specie