Celcuity Inc. · NASDAQ:CELC
Celcuity — Investor Presentation (March 2024)
57 slides from Celcuity's investor presentation, March 2024
Slide 1: Unlocking the Potential of Treating Cancers That Involve the PI3K/mTOR Pathway
Unlocking the Potential of Treating Cancers That Involve the PI3K/mTOR Pathway Corporate Presentation March 2024
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, including but not limited to current beliefs, expectations and assumptions rega
Slide 3: 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, cytotoxic, and well tolerated PAM inhibitor 2 • Very compelling data in 1L (mPFS 48 months) and 2L (mPFS 12.9 month
Slide 4: Unlocking the Potential of Treating Cancers That Involve the PI3K/AKT/mTOR Pathway
Unlocking the Potential of Treating Cancers That Involve the PI3K/AKT/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/AKT/mTOR (PAM) Proportion of alterations Breast and prosta
Slide 5: 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 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 pathway in PAM revenue potential comparable to solid tumors CDK4/6 & AR therapies $10.1B 38% $8.8B % Tumors 2022 Global w/Altered Revenues2 Pathways1 8% 5% 4% $0.5B Target PAM HER2 EGFR ALK Target PA
Slide 7: 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 8: Gedatolisib Has a Highly Differentiated Mechanism of Action and Potency
Gedatolisib Has a Highly Differentiated Mechanism of Action and Potency Results in superior cytotoxicity vs. single node PAM inhibitors Cell-Free Biochemical Dose Response Analysis Live Cell Proliferation Rate Dose Response Analysis7 IC50 (nM)1 Average values for 14 PIK3CA MT and 14 PIK3CA WT breast
Slide 9: 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 10: 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 11: Gedatolisib PK Properties and IV Administration Optimize Safety Profile
Gedatolisib PK Properties and IV Administration Optimize Safety Profile Lower toxicity vs. approved PI3K inhibitors 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 o >95% lowe
Slide 12: 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 13: 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 14: Clinical Development Programs
Clinical Development Programs 2nd Line HR+/HER2- Advanced Breast Cancer 2nd Line Metastatic Castration Resistant Prostate Cancer Pivotal Phase 3 clinical trial for gedatolisib with Phase 1b/2 clinical trial for gedatolisib with fulvestrant +/- palbociclib is enrolling darolutamide is enrolling Enr
Slide 15: Addressable Patient Population in Breast and Prostate Cancer
Addressable Patient Population in Breast and Prostate Cancer 552,000 US, EU5, and Japan Patient Populations Metastatic HSPC Aggregate Patient Populations 395,000 341,000 nmCRPC nmCRPC HR+/HER2- HR+/HER2- HR+/HER2- Stage II/III Stage II/III Stage II/III 225,000 Early BC Early BC Early BC Metastatic M
Slide 16: 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 115,875 101,135 82,880 Addressable 92,195 93, 382 Patient 72,890 61,217 Population 49,334 53,430 48,707 53,848 38,508 31,569 28,448 74,000 43,488 16,678 54,658 44,048 47,7
Slide 17: Gedatolisib for Advanced Breast Cancer (ABC)
Gedatolisib for Advanced Breast Cancer (ABC) 17
Slide 18: 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 19: 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 Localized and Regional Advanced and Metastatic Stage I-III Stage III (inoperable) or Stage IV Disease Low Recurrent Higher 1st 2nd 3rd 4th ~25% Recur Risk Recurrent Ri
Slide 20: Limited Benefit for 1st Line ET Resistant or 2nd Line HR+/HER2- ABC Patients
Limited Benefit for 1st Line ET Resistant or 2nd Line HR+/HER2- ABC Patients Significant need for better therapeutic options st 1 Line Treatment Outcomes 2nd Line Treatment Outcomes (post CDK4/6 treatment) 27.6 25.3 mPFS 14.5 (mo) 7.3 7.3 5.5 3.8 1.9 Palbociclib Ribociclib Palbociclib 3.8 +months Al
Slide 21: Review of Phase 1b Data
Review of Phase 1b Data Gedatolisib + Palbociclib + Fulvestrant/Letrozole 21
Slide 22: Treatment Strategy: Simultaneous Blockade of PAM, ER, & CDK4/6 Pathways
Treatment Strategy: Simultaneous Blockade of PAM, ER, & CDK4/6 Pathways Treatment Rationale • Blockade of interdependent ER, PI3K, mTOR & CDK signaling pathways is required to optimize anti-tumor control • PAM inhibition: • Blockades pathway and limitss activation when ER or CDK4/6 is inhibited • In
Slide 23: 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 24: 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 25: 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 26: 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 27: 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 • Alpelisib – 26% discontinued 1 (180 mg IV, 3 weeks on, one week off) • Everolimus
Slide 28: 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 29: 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 30: 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 31: 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 1L 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% So
Slide 32: Phase 3 Study Design VIKTORIA-1
Phase 3 Study Design VIKTORIA-1 32
Slide 33: 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 34: 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 35: Relevant Comparisons to VIKTORIA-1 Controls
Relevant Comparisons to VIKTORIA-1 Controls 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 / M WT / MT PIK3
Slide 36: 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 37: 200+ Sites Across 20 Countries
200+ Sites Across 20 Countries Europe North America Asia Pacific South America 37
Slide 38: Gedatolisib for Prostate Cancer
Gedatolisib for Prostate Cancer 38
Slide 39: 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 40: 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 41: 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 42: 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 • Favorable clinical data in mCRPC with PAM inhibitors provides “proof-of-concept
Slide 43: 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: N =
Slide 44: 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 45: ~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 45
Slide 46: Additional Early Phase Clinical Data
Additional Early Phase Clinical Data 46
Slide 47: 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
Slide 48: Gedatolisib + Trastuzumab Biosimilar in 3L+ HER2+ ABC Patients (N=17)
Gedatolisib + Trastuzumab Biosimilar in 3L+ HER2+ ABC Patients (N=17) 59% ORR and 83% clinical benefit rate Best Response Duration of Response * * Target lesion decreased by 63% but a new leptomeningeal seeding occurred. o 10 of 17 (59%) showed partial response (PR) o Median duration of response 7.1
Slide 49: Leading cancer KOLs are participating in our research
Leading cancer KOLs are participating in our research Mark Pegram M.D. Ph.D. Sara Hurvitz M.D. Ben Ho Park M.D., Ph.D. Adam Brufsky M.D., Ph.D. Lee Schwartzberg M.D. Clinical Advisory Board Hung Khong M.D. Bora Lim M.D. Mothaffar Rimawi M.D. Alberto Montero M.D. Scientific Advisory z Board Carol Lan
Slide 50: Leadership Team: Track Record of Developing Approved Therapies and Building Companies
Leadership Team: Track Record of Developing Approved Therapies and Building Companies Brian Sullivan Igor Gorbatchevsky, MD Fred Kerwood Chief Executive Officer Chief Medical Officer VP, Program Management Co-Founder Lance Laing, PhD Bernhard Lampert, PhD Nadene Zack Chief Scientific Officer VP, Pha
Slide 51: 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, cytotoxic, and well tolerated PAM inhibitor 2 • Very compelling data in 1L (mPFS 48 months) and 2L (mPFS 12.9 month
Slide 52: Live tumor cells contain infinitely more data than fragmented cells
Live tumor cells contain infinitely more data than the fragmented cells current cancer diagnostics use The CELsignia platform captures this data 52
Slide 53: Researchers recognize need for alternatives to genomic analysis
Researchers recognize need for alternatives to genomic analysis Complexity of signaling pathway networks requires much greater data to characterize than genomics can provide “It is becoming increasingly clear that pathways rather than individual genes govern the course of tumorigenesis.” Kornelia Po
Slide 54: CELsignia – the first 3rd generation diagnostic
– the first 3rd generation diagnostic Measures dynamic cell signaling activity to identify cancer drivers genomic tests cannot detect Live Tumor Cell Signaling Algorithmic Cells Isolated Quantified Analysis >100,000 patient tumor cells are Cell pathways are activated to A proprietary algorithm analy
Slide 55: Current Molecular Diagnostics vs. CELsignia – HER2 Example
Current Molecular Diagnostics vs. CELsignia – HER2 Example CELsignia identifies new sub-group of patients with HER2 driven cancer FISH HER2 Dx CELsignia HER2 Activity FISH+ CELsignia+ (1 pathway gene ) (4 hours of pathway signaling events) 15% 15%-20% $9 billion CELsignia identifies new $Billions ad
Slide 56: Key research discoveries drive test development
Key research discoveries drive test development CELsignia platform provides powerful tool to discover new cancer sub-types and mechanisms Specific target mutations Mutations often don’t lead to Drug resistance mechanisms (e.g. HER2+) not required for oncogenic signaling characterized oncogenic signa
Slide 57: Celcuity is focused on unlocking the potential of treating cancers that involve the PI3K/mTOR pathway
Celcuity is focused on Our third-generation cellular unlocking the potential analysis platform unravels complex oncogenic activity of treating cancers that molecular tests can’t detect. involve the PI3K/mTOR pathway We harvest these insights to develop new targeted therapies for cancer patients 57