Celcuity Inc. · NASDAQ:CELC
Celcuity — Investor Day (September 2023)
96 slides from Celcuity's investor day presentation, Sep 21, 2023
Slide 1: Celcuity Science Day
Celcuity Science Day Unlocking the Potential of Treating Cancers with PI3K/mTOR Involved Signaling September 21, 2023
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial condition. Forward-looking statements include but are not limited to statements based on c
Slide 3: Celcuity Leadership Team and External Speakers Participating Today
Celcuity Leadership Team and External Speakers Participating Today Celcuity Participants External Key Opinion Leaders Brian Sullivan Lance Laing, PhD Igor Gorbatchevsky, MD Sara Hurvitz, MD Karim Fizazi, MD, PhD Chief Executive Officer Chief Scientific Officer Chief Medical Officer Professor of Medi
Slide 4: Agenda
Agenda Topic Session Presenter Overview of Gedatolisib’s Potential Brian Sullivan Importance of PI3K/mTOR as an Anti-Cancer Target Lance Laing, PhD Scientific Overview Gedatolisib Differentiation – Nonclinical Lance Laing, PhD Gedatolisib PK and Safety Overview Igor Gorbatchevsky, MD KOL Presentatio
Slide 5: Introduction and Overview
Introduction and Overview Brian Sullivan CEO and Co-Founder 5
Slide 6: Focused on Treating Cancers Involving the PI3K/mTOR Pathway
Focused on Treating Cancers Involving the PI3K/mTOR Pathway Largest untapped drug One of the most important Most highly altered of all development opportunity oncogenic pathways signaling pathways1 in solid tumors PI3K/mTOR (PAM) regulates Proportion of alterations Breast and prostate cancers key me
Slide 7: Difficult to Safely and Efficaciously Inhibit PI3K/mTOR
Difficult to Safely and Efficaciously Inhibit PI3K/mTOR Maximum efficacy requires inhibition of all Class I PI3K isoforms and mTORC1 and mTORC2 Multiple pathway components Therapeutic window for oral must be targeted PI3K/mTOR inhibitors is narrow Feedforward and feedback loops between Difficult to
Slide 8: Gedatolisib is a Potential First-in-Class PI3K/mTOR Inhibitor
Gedatolisib is a Potential First-in-Class PI3K/mTOR Inhibitor Breakthrough Therapy Designation granted for 2L HR+/HER2- advanced breast cancer indication Highly Differentiated Compelling Efficacy Well-Tolerated Addressing Large Mechanism Patient Populations • Inhibits all PI3K/mTOR • Gedatolisib + E
Slide 9: Current Clinical Development Programs
Current Clinical Development Programs 2nd Line HR+/HER2- Advanced 2nd Line Metastatic Castration Resistant Breast Cancer (ABC) Prostate Cancer (mCRPC) Pivotal Phase 3 clinical trial for gedatolisib with Phase 1b/2 clinical trial for fulvestrant +/- palbociclib is enrolling gedatolisib with darolutam
Slide 10: Mechanism of Action & Potency Induce Superior Cytotoxicity
Mechanism of Action (MOA) & Potency Induce Superior Cytotoxicity Gedatolisib vs. approved PAM inhibitors assessed in 34 breast and prostate cancer cell lines1 Optimal Superior Superior MOA Potency Cytotoxicity 6 vs. 1 >25-300x more 2-4x more PAM pathway potent in cytotoxic nodes inhibited2 vitro3 in
Slide 11: Gedatolisib Is Well Tolerated - Unlike Earlier PI3K/mTOR or Pan-PI3K Inhibitors
Gedatolisib Is Well Tolerated - Unlike Earlier PI3K/mTOR or Pan-PI3K Inhibitors Optimal PK IV Optimal liver Superior Properties Administration & GI exposure Tolerability 11
Slide 12: 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 pathway in Gedatolisib has revenue potential solid tumors comparable to CDK4/6 & AR therapies $10.1B 38% $8.8B % Tumors 2022 Global w/Altered Revenues2 Pathways1 8% 5% 4% $0.4B Target PAM HER2 EGFR A
Slide 13: Addressable Patient Population in Breast and Prostate Cancer
Addressable Patient Population in Breast and Prostate Cancer US, EU5, and Japan Patient Populations 539,000 Metastatic HSPC Aggregate Patient Populations 382,000 328,000 nmCRPC nmCRPC HR+/HER2- HR+/HER2- HR+/HER2- Stage II/III Stage II/III Stage II/III Early BC Early BC Early BC 212,000 Metastatic M
Slide 14: Multiple potential blockbuster indications in both tumor types
Multiple potential blockbuster indications in both tumor types HR+/HER2- Breast Cancer Advanced Prostate Cancer 156,880 US EU5+J 115,875 101,300 82,880 101,135 Addressable 89,040 Patient 61,217 80,908 58,800 Population 53,430 47,040 53,848 42,744 28,448 74,000 52,500 54,658 47,705 42,000 38,164 25,4
Slide 15: Key Themes for Today's Meeting
Key Themes for Today’s Meeting Significant untapped potential to effectively treat PAM pathway involved cancers 1 • The PAM pathway is one of the most important, yet underdeveloped, targets in cancer 2 • Gedatolisib’s differentiated MOA and PK profile result in a highly potent and cytotoxic PAM inhi
Slide 16: The Importance of the PI3K/mTOR Pathway as a Cancer Driver
The Importance of the PI3K/mTOR Pathway as a Cancer Driver Lance Laing, PhD Chief Science Officer and Co-Founder 16
Slide 17: The PAM Pathway Regulates Critical Cell Functions
The PAM Pathway Regulates Critical Cell Functions PAM – PI3K/AKT/mTOR pathway PAM is a “command and control” center of critical cellular processes. PI3K/ AKT/ mTOR Hoxhaj et al. 2020, Nat Rev Cancer. 20(2):74-88; Fruman et al. 2017 Cell 170(4): 605–635; Manning and Toker 2017 Cell 169(3): 381–405; K
Slide 18: Tumors Rely on Metabolic Changes Controlled by PAM Pathway
Tumors Rely on Metabolic Changes Controlled by PAM Pathway Activity controlled by the PAM pathway creates a pro-tumor microenvironment Glucose Tumor cells require tremendous The PAM pathway regulates glucose amounts of glucose relative to consumption, which makes it a normal cells fundamental tumor
Slide 19: PAM has Multiple Signaling Nodes that Provide Functional Redundancy
PAM has Multiple Signaling Nodes that Provide Functional Redundancy Redundancy ensures pathway function is maintained if a single node becomes disrupted GPCR RTK • PAM pathway primary signaling nodes PIP2 PIP3 • PTEN • Class I PI3K isoforms – α,β,γ,δ PI3K PTEN PDK1 Activation by DNA damage • mTORC1
Slide 20: Node Redundancy Requires PI3Kα/β/γ/δ and mTORC1/2 Inhibition
Node Redundancy Requires PI3Kα/β/γ/δ and mTORC1/2 Inhibition Intrinsic pathway complexity challenges single node control therapeutic approach • Each PAM node has a critical role in Adaptive response of PAM nodes maintaining viability when a single PAM node inhibited • Inhibition of individual nodes
Slide 21: Gedatolisib Differentiation Review
Nonclinical Data Gedatolisib Differentiation Review 21
Slide 22: Gedatolisib Has a Highly Differentiated Mechanism of Action
Gedatolisib Has a Highly Differentiated Mechanism of Action Inhibits six different PAM nodes to induce comprehensive pathway blockade Gedatolisib vs PAM Node Inhibitors IC50 (nM)1 Gedatolisib is Potent Against all Node Gedatolisib2 Alpelisib3 Everolimus4 Capivasertib5 Class I PI3K Isoforms and mTORC
Slide 23: Breast Cancer Cell Lines: Evaluated Gedatolisib and Node-Specific Inhibitors
Breast Cancer Cell Lines: Evaluated Gedatolisib and Node-Specific Inhibitors Gedatolisib exerts superior cytotoxic effects at all concentrations relative to other PAM inhibitors • Assessed cytotoxic and cytostatic 28 Cell Lines Evaluated effects using growth rate metric AKT1/2/3 Gedatolisib Alpelisi
Slide 24: Breast Cancer Cell Lines: Gedatolisib is >300x more potent, 2X more cytotoxic
Breast Cancer Cell Lines: Gedatolisib is >300x more potent, 2X more cytotoxic Average Values for 28 Breast Cancer Cell Lines Potency Efficacy Low High Cytostatic Cytotoxic 0-100% 101%-200% GR50 (nM) Max Cell Growth Inhibition1 Gedatolisib vs. Geda Alpe Capi Evero Geda Alpe Capi Evero Other PAM Inhib
Slide 25: Breast Cancer Mini-PDX Models: Compared PAM Inhibitors
Breast Cancer Mini-PDX Models: Compared PAM Inhibitors Gedatolisib induced higher tumor growth inhibition than node specific inhibitors in PIK3CA WT and MT models PDX361836 PDX362153 • Gedatolisib induced significant tumor PIK3CA WT, PTEN WT PIK3CA MT , PTEN MT growth inhibition (TGI) in both wild t
Slide 26: Prostate Cancer Cell Lines: Compared PAM Inhibitors
Prostate Cancer Cell Lines: Compared PAM Inhibitors Gedatolisib exerts superior cytotoxic effects at all concentrations relative to other PAM inhibitors • Assessed cytotoxic and cytostatic effects using growth rate metric • Avoids the confounding effects of individual cell line proliferation rates G
Slide 27: Prostate Cancer Cell Lines: Gedatolisib is ~20-65x more potent, more cytotoxic
Prostate Cancer Cell Lines: Gedatolisib is ~20-65x more potent, more cytotoxic Average Values for Six Prostate Cancer Cell Lines (22RV1, MDA-PCa-2b, DU145, LNCaP, C4-2, PC3) Gedatolisib vs. Other PAM Inhibitors Potency Efficacy Cytotoxic • More cytotoxic than other PAM inhibitors Cytostatic 0-100% 1
Slide 28: In Vivo Activity of Gedatolisib in Prostate Cancer Xenograft Models
In Vivo Activity of Gedatolisib in Prostate Cancer Xenograft Models Gedatolisib induced >80% tumor growth inhibition (TGI) regardless of PTEN or AR status 800 22RV1 2000 PC3 2000 C4-2 C4-2 (PTEN-WT, AR-v7+) (PTEN-loss, AR-null) (PTEN-loss, AR-mt) (PTEN-loss) Tumor Volume (mm3) 600 1500 1500 400 1000
Slide 29: PK/PD Xenograft Tumor Tissue Analysis During Dosing Interval
PK/PD Xenograft Tumor Tissue Analysis During Dosing Interval Gedatolisib concentration remains above cytotoxic and pathway inhibition threshold during dosing interval Effect of gedatolisib on PAM pharmacodynamic markers in PC3 xenograft tissue PK Gedatolisib (nM) in Xenograft Tumor 4EBP1 pRPS6 Tissu
Slide 30: PAM Reduces Immune System Function in Tumors
PAM Reduces Immune System Function in Tumors Causes tumor cells to generate biochemical factors that negatively affect tumor microenvironment (TME) PAM pathway impact on TME is likely a major factor that causes breast and prostate tumors to be immunologically “cold” Increases lactate production
Slide 31: Gedatolisib Favorably Impacts Tumor Microenvironment
Gedatolisib Favorably Impacts Tumor Microenvironment PAM inhibition decreases O2 and glucose consumption and lactate production Oxygen Consumption Rate Oxygen Concentration 35 A TME with low O2, low glucose, 180 and high lactate is correlated with OCR fm/mm2/s 30 immuno-suppression, low anti-tumor O
Slide 32: Gedatolisib Increases Immune Cell Tumor Infiltration and Activation
Gedatolisib Increases Immune Cell Tumor Infiltration and Activation Profiled CD45+ immune cell populations in tumor, bone marrow, peripheral blood Proportions of CD45+ anti-tumor immune cell subsets in tumor Day 10 Day 17 Control Geda P-Value Control Geda P-Value % CD45+ 4.7 10.9 0.03 - - - % DC 9.0
Slide 33: Key Takeaways: Non-clinical
Key Takeaways: Non-clinical Gedatolisib is highly potent and cytotoxic; controls factors that induce immunosuppression in TME PAM is Complex • PAM pathway is an important driver of metabolic activities that support tumor cell proliferation Pathway • Multi-node inhibition is required to address pathw
Slide 34: PK and Safety Overview of Gedatolisib
PK and Safety Overview of Gedatolisib Igor Gorbatchevsky, MD Chief Medical Officer 34
Slide 35: Gedatolisib's PK and Metabolic Profile
Gedatolisib’s PK and Metabolic Profile Stable chemical structure leads to optimized PK profile PK characteristics in humans • T ½ ≈ 37 hours • Dose-proportional and predictable PK exposure • No accumulation after multiple doses • Minimal inter-patient variability in PK parameters Metabolism • Minima
Slide 36: Gedatolisib Key PK Properties and Safety Metrics vs. Approved PI3Ki
Gedatolisib Key PK Properties and Safety Metrics vs. Approved PI3Ki Differentiated favorable PK profile leads to lower toxicity Gedatolisib1 Alpelisib2,3 Copanlisib3 Duvelisib3 Idelalisib3 Gedatolisib vs. PI3K-α and pan-PI3K drugs Pan-PI3K (single-agents) Target(s) PI3K-α Pan-PI3K PI3K-δ PI3K-δ mTOR
Slide 37: Gedatolisib Single Agent Safety Profile
Gedatolisib Single Agent Safety Profile Phase 1 Trial: gedatolisib at maximum tolerated dose (MTD) - 154 mg weekly (IV)1 MTD Arm (n=42) • Limited incidence of Grade 3 adverse events Related TEAE’s > 20% • The most frequent AE, stomatitis, is manageable Grade 1 Grade 2 Grade 3/4 with prophylactic ste
Slide 38: Safety Data for Single-Agent Gedatolisib vs. Single Node PAM Inhibitors
Safety Data for Single-Agent Gedatolisib vs. Single Node PAM Inhibitors Fewer patients reported AE when treated with gedatolisib as single agent compared to other PAMi gedatolisib alpelisib everolimus capivasertib Grade 1-2 (solid); Grade 3+ (dots) Percent of Subjects with AE 78 17 55 7 46 43 40 40
Slide 39: Prostate Cancer
Prostate Cancer 39
Slide 40: Current Standards of Care in mCRPC and Unmet Clinical Needs
Current Standards of Care in mCRPC and Unmet Clinical Needs Karim Fizazi, MD, PhD Professor of Medicine, University of Paris-Saclay GETUS President Head, GU Group, Institute Gustav Roussy University of Paris Saclay 40
Slide 41: 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 42: 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 nmCRPC non-metastatic castration resistant Localized Systemic Rising PSA mCRPC mCRPC Disease Prostate or Tumor Biochemical 1L 2L Stage Cancer recurrence Progressio
Slide 43: Limited Benefit for 2L HRR- mCRPC Patients After Treatment with AR Inhibitor
Limited Benefit for 2L HRR- mCRPC Patients After Treatment with AR Inhibitor Significant need for better therapeutic options st 1 Line Treatment Outcomes 2nd Line Treatment Outcomes (post AR inhibitor treatment) 20.0 mPFS 7.3 months 16.5 ORR 17% mPFS (mo) 6.7 5.6 5.6 5.5 Drugs 3.8 months Xtandi 1 Zy
Slide 44: 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 PI3K/mTOR + AR Inhibition Treatment Rationale • AR inhibition increases PAM pathway signaling 2 • For patients who progressed o
Slide 45: PAM Inhibitor Development Efforts for mCRPC Have Focused on AKT
PAM Inhibitor Development Efforts for mCRPC Have Focused on AKT Reflects high incidence of PTEN alterations in mCRPC that AKT inhibition can address The AKT inhibitor, ipatasertib, has been extensively evaluated in prostate cancer AKT inhibition can lead to reactivation of the PAM pathway throug
Slide 46: Clinical Trial Results for PAM Inhibitors After Progression on AR Therapy
Clinical Trial Results for PAM Inhibitors After Progression on AR Therapy Evidence of PAM pathways involvement and sensitivity to PAM inhibitors in mCRPC Line of Patient Overall Results Study Regimens N Comments Therapy Population (Months rPFS) 10.5 vs. 5.5 months Samotolisib efficacious despite o
Slide 47: Key Takeaways
Key Takeaways Strong scientific rationale to combine a pan-PI3K/mTOR inhibitor with a next generation AR inhibitor • Efficacy of current 2L therapies for mCRPC post-ARi is limited; new therapeutic approaches are needed 1 • Docetaxel • AR inhibitors mPFS: 6-7 months mPFS: 5-6 months 2 • Extensive non
Slide 48: Clinical Overview of Gedatolisib for mCRPC
Clinical Overview of Gedatolisib for mCRPC Igor Gorbatchevsky, MD Chief Medical Officer 48
Slide 49: Strong Scientific Rationale to Evaluate Gedatolisib in mCPRC
Strong Scientific Rationale to Evaluate Gedatolisib in mCPRC Gedatolisib’s clinical efficacy in breast cancer correlated with strong activity in Favorable clinical data in mCRPC Xenograft data in PR models is nonclinical tumor models with PAM inhibitors provides consistent with in vivo data – “proof
Slide 50: CELC-G-201: Phase 1b/2 Trial Design Overview
CELC-G-201: Phase 1b/2 Trial Design Overview Evaluating gedatolisib combined with darolutamide, a potent next generation androgen receptor inhibitor Phase 1b Phase 2 Determine RP2D, assess Dose Expansion safety and tolerability Arm 1 Gedatolisib 120 mg + Darolutamide 600 mg BID Primary Endpoint: Pat
Slide 51: ~12 Sites Across US and Europe
~12 Sites Across US and Europe Expect to enroll first patient Q1 2024 and announce initial data 1H 2025 UK, France, Spain USA 51
Slide 52: Darolutamide is More Potent and Better Tolerated than SOC 1L AR Inhibitors
Darolutamide is More Potent and Better Tolerated than SOC 1L AR Inhibitors Bayer is collaborating with Celcuity and will supply darolutamide for the trial Darolutamide Abiraterone Enzalutamide Approved Indications nmCRPC, mHSPC mCRPC, mHSPC mCRPC, nmCRPC, mHSPC IC50 1 11 nM 2 72 nM 3 86 nM 2 Most Co
Slide 53: Breast Cancer
Breast Cancer 53
Slide 54: Current Standards of Care in HR+/HER2- Advanced Breast Cancer and Unmet Clinical Needs
Current Standards of Care in HR+/HER2- Advanced Breast Cancer and Unmet Clinical Needs Sara A. Hurvitz, MD, FACP Professor of Medicine Head, Division of Hematology and Oncology Senior Vice President, Clinical Research Division Department of Medicine, UW Medicine Fred Hutchinson Cancer Center 54
Slide 55: ER, CDK4/6, & PI3K/mTOR are Interdependent Drivers of HR+/HER2- ABC
ER, CDK4/6, & PI3K/mTOR are Interdependent Drivers of HR+/HER2- ABC Dysregulation of these pathways promotes excessive cell proliferation and resistance to apoptosis ER and PI3K/mTOR CDK4/6, ER and PI3K/mTOR • Activation of the PI3K/mTOR pathway • Estrogen promotes cyclin D1 transcription induces es
Slide 56: Drug Development Activities Reflect Important Role of ER, CDK4/6 and PAM Pathway
Drug Development Activities Reflect Important Role of ER, CDK4/6 and PAM Key targeted therapy approval milestones for HR+/HER2- ABC 1977 1997 2002 2012 2015 2019 2023 SERM AI SERD (IM) SERD (oral) ER Tamoxifen Letrozole Fulvestrant Elacestrant Pathway PI3K/mTOR mTORC1 PI3Kα Everolimus Alpelisib CDK4
Slide 57: HR+/HER2- Breast Cancer Treatment Landscape
HR+/HER2- Breast Cancer Treatment Landscape Local and Regional Advanced and Metastatic Stage I-III Stage III (inoperable) or Stage IV ~200,000 Cases diagnosed annually in USA ~50,000 Cases diagnosed annually in USA Low Recurrent Risk Higher Recurrent Risk 2nd Line 1st Line 3rd Line 4th Line Adjuvant
Slide 58: Limited Benefit for 2nd Line HR+/HER2- ABC Patients Post-CDK4/6 Treatment
Limited Benefit for 2nd Line HR+/HER2- ABC Patients Post-CDK4/6 Treatment Significant need for better therapeutic options st 1 Line Treatment Outcomes 2nd Line Treatment Outcomes (post CDK4/6 treatment) 28.2 27.6 25.3 mPFS 14.5 (mo) 7.3 5.5 3.8 1.9 Abemaciclib Palbociclib Ribociclib 3.8 months Alpel
Slide 59: Key Unmet Needs for Patients with HR+/HER2- ABC
Key Unmet Needs for Patients with HR+/HER2- ABC Key Questions Key Unmet Needs Key Questions • Improve mPFS after progression on CDK4/6 • What role can PI3K/mTOR inhibitors play? inhibitors • Is retreatment with CDK4/6 inhibitors beneficial? • PIK3CA WT patients: 2 – 5.5 months • PIK3CA MT patients:
Slide 60: Initial PAM Drug Development in ABC Focused on PI3K/mTOR Inhibitors
Initial PAM Drug Development in ABC Focused on PI3K/mTOR Inhibitors Toxicity, PK, and efficacy limitations resulted in shift towards PAM single-node inhibitors 1st 2nd 3rd Single PI3K/mTOR Pan-PI3K Node PI3K/mTOR Gen Gen Gen Programs halted at Programs halted at Approved Phase 3 Phase 3 Phase 1/2 Ph
Slide 61: Clinical Trial Results for PAM Inhibitors After Progression on CDK4/6 Therapy
Clinical Trial Results for PAM Inhibitors After Progression on CDK4/6 Therapy Evidence of PAM pathways involvement and sensitivity to PAM inhibitors in HR+/HER2- ABC Patient PIK3CA mPFS Therapies N ORR Comments Status (months) Gedatolisib + Palbociclib + WT and MT 27 63% 12.9 Fulvestrant 1 • Data fo
Slide 62: Therapy after Progression on a CDK4/6i
Therapy after Progression on a CDK4/6i Is there a benefit to retreating with CDK4/6i with a different ET or different CDK4/6i or both? Therapies Patient N Results Comments (Study) Population Ribociclib + 5.3 vs. 2.8 months • MAINTAIN suggests ribociclib after palbo Prior palbociclib 103 with a diffe
Slide 63: Therapy after Progression on a CDK4/6i
Therapy after Progression on a CDK4/6i What role should oral SERD’s play? Therapies Prior mPFS Prior CDK4/6i Comments (Study) Fulvestrant ESR1 MT Elacestrant 3.8 vs 1.9 months vs ET 100% 30% HR = 0.65, P=0.005 • Data to date not as promising as expected (EMERALD)1 when development of this drug class
Slide 64: Therapy after progression on a CDK4/6i
Therapy after progression on a CDK4/6i When should an ADC be used? Therapies Patient Population Prior Therapy N mPFS Comments (Study) Progressed on prior 70% prior Trastuzumab chemotherapy CDK4/6i • Goal is to utilize endocrine backbone Deruxtectan 10.1 vs 5.4 months therapy as long as possible 480
Slide 65: Key Takeaways
Key Takeaways A more effective PAM inhibitor may offer best opportunity to improve outcomes for HR+/HER2- ABC 1 • The PAM pathway is key driver of breast cancer and is linked to ER and CDK4/6 pathways o Approval of multiple PAM inhibitors confirm relevance of pathway • The two approved PAM therapies
Slide 66: Clinical Data for Gedatolisib in Breast Cancer
Clinical Data for Gedatolisib in Breast Cancer Igor Gorbatchevsky, MD Chief Medical Officer 66
Slide 67: PI3K/mTOR, ER, and CDK4/6 are Interdependent Signaling Pathways
PI3K/mTOR, ER, and CDK4/6 are Interdependent Signaling Pathways PI3K/mTOR is a key resistance mechanism to estrogen and CDK4/6 therapies PI3K/mTOR + ER + CDK4/6 Inhibition Treatment Rationale • Simultaneously blocking interdependent ER, PI3K, mTOR & CDK signaling pathways in ER+ breast cancer addres
Slide 68: Non-Clinical Data Consistent with Treatment Hypothesis
Non-Clinical Data Consistent with Treatment Hypothesis Gedatolisib with palbociclib and fulvestrant in ER+/PIK3CA mutated breast cancer mouse xenograft Tumor Growth Inhibition Maintenance of Tumor Suppression (during dosing) (65 Days post-dosing) G+P+F, G+P, G+F > 120% G+P+F and G+P
Slide 69: B2151009: Phase 1b Study (138 patients)
B2151009: Phase 1b Study (138 patients) Provided Data in Treatment Naïve and Prior CDK4/6 Treated Patients with HR+/HER2- ABC Expansion (4 Arms) Dose Escalation N = 103 (2 cohorts) Arm A N = 35 1st Line: palbo + letrozole + gedatolisib Letrozole Cohort palbociclib + letrozole + gedatolisib Arm B 2L+
Slide 70: B2151009 Expansion Arms: Baseline Characteristics
B2151009 Expansion Arms: Baseline Characteristics Arm A Arm B Arm C Arm D (N=31) (N=13) (N=32) (N=27) Tumor, Node, Metastasis (TNM) Current Stage, n (%) Stage IV 31 (100) 13 (100) 32 (100) 27 (100) Prior therapies for ABC, n (%) Prior Chemotherapy 1 (3.2) 4 (30.8) 15 (46.9) 5 (18.5) Prior Endocrine
Slide 71: B2151009 Expansion Arms: Patient Treatment Discontinuation
B2151009 Expansion Arms: Patient Treatment Discontinuation Arm A Arm B Arm C Arm D Reasons for treatment discontinuation, n (%) (N=31) (N=13) (N=32) (N=27) Progression or relapse 12 (38.7) 10 (76.9) 24 (75.0) 20 (74.1) Global Deterioration 2 (6.5) 0 1 (3.1) 2 (7.4) Death a 0 0 0 1 (3.7) Adverse Even
Slide 72: ORR and PFS in Each Expansion Arm Was Superior to SOC
ORR and PFS in Each Expansion Arm Was Superior to SOC Results from Arm D - 63% ORR and 12.9 months PFS – provide basis for Phase 3 clinical trial B2151009 Expansion Arms Efficacy Summary (N=103) Arm A Arm B Arm C Arm D 2L+ 2L/3L 2L/3L Prior Therapy 1L CDKi-naive CDKi-pretreated CDKi-pretreated n (Fu
Slide 73: 2nd Line HR+/HER2- Advanced Breast Cancer
2nd Line HR+/HER2- Advanced Breast Cancer 73
Slide 74: B2151009 Arm D: Safety Summary for Phase 3 Dosing
B2151009 Arm D: Safety Summary for Phase 3 Dosing G + P + F was well tolerated overall; < 4% discontinuation rate Arm D (n=27) • Discontinuation of gedatolisib due to AE - <4% Gedatolisib + Palbociclib + Fulvestrant (180 mg IV, 3 weeks on, one week off) • Alpelisib – 25% discontinued 1 Related TEAE’
Slide 75: Arm C and D Had Significant Differences in Baseline Characteristics
Arm C and D Had Significant Differences in Baseline Characteristics Both arms enrolled patients who had received prior CDK4/6 therapy Baseline Characteristics That Differed Significantly Between Arm C and D • 61% shorter duration on immediate prior therapy in Arm C vs. D Arm C Arm D • 5.2 vs. 13.5 m
Slide 76: Analysis of Arm C and D Patients with Similar Prior Treatment Durations
Analysis of Arm C and D Patients with Similar Prior Treatment Durations Enables isolation of effect of the different dosing schedules used in each arm Duration of Immediate Prior Treatment (DIPT) DIPT <180 Days DIPT <365 Days Arm C Arm D Arm C Arm D Key Finding # Evaluable patients with DIPT <185 12
Slide 77: Forest Plot for Model-Selected Subgroups
Forest Plot for Model-Selected Subgroups Dose schedule effect (Arm D over C) is observed in all critical subgroups selected by a logistic regression model Approach • Tested 8 factors to identify ones affecting ORR • Of the 8 factors tested, 3 met significance criteria • Duration of immediate prior t
Slide 78: Gedatolisib + Palbociclib + Fulvestrant in 2nd/3rd Line HR+/HER2- ABC Patients
Gedatolisib + Palbociclib + Fulvestrant in 2nd/3rd Line HR+/HER2- ABC Patients Data from Arm D with Phase 3 regimen compares favorably to published data with current SOC 100 mPFS Tumor Size Change 12.9 months ORR = 63% (17/27) Progression free survival (%) 80 60 40 % Change from Baseline 60 20 40 0
Slide 79: Gedatolisib Combo vs. SOC for 2L HR+ / HER2- ABC Post-CDKi
Gedatolisib Combo vs. SOC for 2L HR+ / HER2- ABC Post-CDKi Gedatolisib Combo Offers Potential for Superior Efficacy Compared to Alternatives Patient Population 2nd Line ER+/HER2- ABC mPFS 12.9 months All Gedatolisib + Fulvestrant + Palbociclib 1 ORR 63% mPFS 7.3 months PIK3CA+ Alpelisib + Fulvestran
Slide 80: Phase 3 Study Design VIKTORIA-1
Phase 3 Study Design VIKTORIA-1 80
Slide 81: Pivotal Trial Design Considerations for 2nd Line HR+/HER2- ABC
Pivotal Trial Design Considerations for 2nd Line HR+/HER2- ABC • Standard-of-care 2nd line treatment is based on PIK3CA status Supports design with multiple • ~35% of patients have disease with PIK3CA mutations primary endpoints in different sub-groups • PFS is accepted primary end point for randomi
Slide 82: VIKTORIA-1 Pivotal Phase 3 Trial Design Overview
VIKTORIA-1 Pivotal Phase 3 Trial Design Overview Arm A Gedatolisib + Palbociclib + Fulvestrant N = 117 PIK3CA Wild-type Arm B Primary Endpoints (WT) R Gedatolisib + Fulvestrant 2h ‘24 PFS 1:1:1 N = 117 A vs. C N = 351 B vs. C Arm C1 Fulvestrant Patients with N = 117 HR+/HER2- ABC who Patients manual
Slide 83: VIKTORIA-1 Pivotal Study Features
VIKTORIA-1 Pivotal Study Features • Global open-label randomized study • Key eligibility criteria: • Any PIK3CA status • Prior CDK4/6i + NSAI Supports indications for gedatolisib and fulvestrant • Any menopausal status with or without palbociclib • < 2 prior endocrine therapy as second or third trea
Slide 84: 200+ Sites Across 20 Countries
200+ Sites Across 20 Countries Europe North America Asia Pacific South America 84
Slide 85: Relevant Comparisons in CDK4/6i Pretreated Patients with ABC
Relevant Comparisons in CDK4/6i Pretreated Patients with ABC B2151009 Study results compared to published data for patients who received prior CDK4/6i Gedatolisib + Palbociclib Alpelisib + Alpelisib + Fulvestrant Fulvestrant + Fulvestrant N=1653 N=525 Fulvestrant Fulvestrant N=271,2 N=1266 N=1217 WT
Slide 86: 1st Line HR+/HER2- Advanced Breast Cancer
1st Line HR+/HER2- Advanced Breast Cancer 86
Slide 87: B2151009 Treatment Naïve Patients: Baseline Characteristics
RESULTS B2151009 Treatment Naïve Patients: Baseline Characteristics Escalation Arm A Expansion Arm A Total Treatment-Naïve (n=11) (N=30) (n=41) Tumor, node, metastasis (TNM) stage, n (%) Stage IV 11 (100.0) 30 (100.0) 41 (100.0) Number of Prior Therapies - Advanced Breast Cancer, n (%) 0 11 (100.0)
Slide 88: B2151009 Treatment Naïve Patients: Treatment Discontinuation
B2151009 Treatment Naïve Patients: Treatment Discontinuation Total Treatment-Naïve Patients Patients who discontinued treatment, n (%) (n=41) Reasons other than AE’s 36 (87.8) Progression or relapse 15 (36.6) Study terminated by sponsor 1 9 (22.0) Withdrawal by Subject 6 (14.6) Global Deterioration
Slide 89: Efficacy in Treatment-Naïve Population Superior to SOC
Efficacy in Treatment-Naïve Population Superior to SOC mPFS of 48.6 months, mDOR of 46.9 months, and ORR of 79% B2151009 Treatment-Naïve Patients (N=41) Escalation Arm A Expansion Arm A Total Treatment Naïve Progression-Free Survival n = 11 n = 30 n = 41 (full analysis set) 45.8 48.6 48.6 Median PFS
Slide 90: Gedatolisib + Palbociclib + Letrozole in 1st Line HR+/HER2- ABC (N=41)
Gedatolisib + Palbociclib + Letrozole in 1st Line HR+/HER2- ABC (N=41)1 Combined 1L data from Esc Arm A + Exp Arm A compares favorably to published data for SOC palbociclib + letrozole2 mPFS Tumor Size Change 48.6 Months ORR = 79% (26/33) 100 90 % Change from Baseline 80 Progression Free Survival (%
Slide 91: Gedatolisib Combo vs. SOC for 1L HR+ / HER2- ABC
Gedatolisib Combo vs. SOC for 1L HR+ / HER2- ABC Gedatolisib Combo Offers Potential for Superior Efficacy Compared to SOC 1st Line HR+/HER2- ABC mPFS 48.6 months Gedatolisib + Palbociclib + Letrozole 1 ORR 79% mPFS 27.6 Months Palbociclib + Letrozole 2 ORR 55% Letrozole 2 mPFS 14.5 mos ORR 44% Sourc
Slide 92: B2151009: 1L and 3L Patient Overview
B2151009: 1L and 3L Patient Overview 1L patient on therapy for 5.1 years; 3L on therapy for 4.3 years; both remain on treatment • 61-year-old female • Initial diagnosis of BC: 2000 • Prior treatment for BC: • 62-year-old female • Radical mastectomy 2000 • Initial diagnosis of BC: 2008 • Adjuvant che
Slide 93: The Celcuity Opportunity
The Celcuity Opportunity celcuity
Slide 94: Don't blame the pathway for limited efficacy and tolerability of PAM inhibitors
Significant untapped potential to treat PAM pathway involved cancers Don’t blame the pathway for • Failures, limited efficacy, and lack of tolerability of limited efficacy and tolerability other PAM inhibitors reflect limitations of the of PAM inhibitors drugs, not irrelevance of pathway o MOA of si
Slide 95: The Celcuity Opportunity
The Celcuity Opportunity Significant untapped potential to effectively treat PAM pathway involved cancers 1 • Gedatolisib’s differentiated MOA and PK profile result in a highly potent and cytotoxic PAM inhibitor 2 • Very compelling data in 1L and 2L patients with HR+/HER2- ABC • Potential to replace
Slide 96: Q&A Participants in Today's Q&A Session
Q&A Participants in Today’s Q&A Session Brian Sullivan Chief Executive Officer and Co-Founder Instructions Submit questions using the Q&A feature on the event page Lance Laing, PhD Chief Scientific Officer and Co-Founder Igor Gorbatchevsky, MD Chief Medical Officer 96