Slide 1: Developing Potentially First-in-Class Rx using 3rd Generation Dx
Developing Potentially First-in- Class Rx using 3rd Generation Dx June 28, 2021
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: Developing Potentially First-in-Class Rx using 3rd Generation Dx
Developing Potentially First-in-Class Rx using 3rd Generation Dx Molecular tests can’t Our platform creates a Enables discovery of Leveraging our platform detect the complex “movie” of signaling new cancer drivers and to develop potentially oncogenic activity activity in live patient expands the mar
Slide 4: Current CELsignia Enabled Drug Programs for Breast Cancer
Current CELsignia Enabled Drug Programs for Breast Cancer Supporting development of six targeted therapies to treat up to 30% of BC patients Treatment Approach Indication Trial Phase 1/1b Phase 2 Phase 3 Drug Sponsor (Pathways) Herceptin + Perjeta 1L + chemo FACT-1 Early (HER2) Breast Cancer 1L Nerl
Slide 5: Integrating CELsignia with Gedatolisib, a Potentially First-in-Class PI3K/mTOR
Integrating CELsignia with Gedatolisib, a Potentially First-in-Class PI3K/mTOR CELsignia CDx Interest in gedatolisib creates more value Unique set of Concluded this was a was prompted while for pharmaceutical circumstances drove unique opportunity to developing our companies than for the timing leve
Slide 6: An integrated CDx and Rx strategy maximizes the impact of targeted therapies
An integrated CDx and Rx strategy maximizes the impact targeted therapies can have on patient outcomes Leverage CELsignia to Use CELsignia to Optimize regimens Discover synergistic develop first-in-class maximize probability using our proprietary drug combinations drugs of getting approvals insights
Slide 7: An Integrated Pipeline of Programs to Advance New Therapies for Breast Cancer
An Integrated Pipeline of Programs to Advance New Therapies for Breast Cancer Treatment approach Drug Indication Population Phase 1/1b Phase 2 Phase 3 (pathways) sponsor Gedatolisib: pan-PI3K/mTOR Gedatolisib + Ibrance + Metastatic 1L/2L Endocrine ER+/HER2- Breast (PI3K/mTOR+CDK4/6+ER) Cancer Gedato
Slide 8: Gedatolisib
Gedatolisib A PI3K/mTOR inhibitor 8
Slide 9: Gedatolisib: Potential First-in-Class PI3K/mTOR Inhibitor
Gedatolisib: Potential First-in-Class PI3K/mTOR Inhibitor Compelling Phase 1b efficacy and safety data o Potent small molecule inhibitor of the PI3K/mTOR pathway administered intravenously Mechanism of Action o Inhibits all isoforms of PI3K and mTOR at low or sub-nanomolar concentrations o 457 patie
Slide 10: PI3K/mTOR is One of the Most Important Oncogenic Pathways
PI3K/mTOR is One of the Most Important Oncogenic Pathways PIK3CA PTEN Loss or Tumor type PI3K/mTOR regulates cell mutation Mutated growth and metabolism PI3K/mTOR regulates cell growth ER+ BC1,2 ~39%1 ~46% and metabolism Endometrial2 ~37% ~82% o Linked to multiple key o Linked to multiple key pathwa
Slide 11: Targeting PI3K and mTOR Efficaciously and Safely is Challenging
Targeting PI3K and mTOR Efficaciously and Safely is Challenging Compensatory pathways enable Therapeutic window for oral PI3K or resistance to PI3K/mTOR inhibition mTOR inhibitors is narrow o Reflects the inherent adaptability and complexity of the o Difficult to achieve optimal pathway inhibition w
Slide 12: Gedatolisib is potent against all PI3K isoforms and mTORC1/2
Gedatolisib is potent against all PI3K isoforms and mTORC1/2 Superior MOA minimizes potential for activation of resistance mechanisms IC50 (nM) (cell-free biochemical dose response analysis) o PIQRAY (Novartis) - PI3K-α inhibitor for 2L PI3K-α PI3K-α therapy in ER+/PIK3CA+ mBC patients Inhibitor (m)
Slide 13: Gedatolisib PK vs. Other PI3K Antagonists
Gedatolisib PK vs. Other PI3K Antagonists PK properties responsible for favorable toxicity profile Comments Gedatolisib1 Alpelisib2 Copanlisib2 Duvelisib2 Idelalisib2 o Hyperglycemia is induced by PI3K-α inhibition and Pan-PI3K increased when drug has high affinity for the liver Target(s) PI3K-α Pan
Slide 14: Gedatolisib for Breast Cancer
Gedatolisib for Breast Cancer 14
Slide 15: ER+/HER2- Metastatic Breast Cancer Patient and Treatment Overview
ER+/HER2- Metastatic Breast Cancer (mBC) Patient and Treatment Overview High unmet medical need for better options for 2L patients who have received a CDK4/6 inhibitor First Line Second Line Treatment mPFS 1 Treatment mPFS 1 ORR ORR (Patient Group) (months) (Patient Group) (months) CDK4/6i + letrozo
Slide 16: Clinical Development Plan Pending FDA Input
Clinical Development Plan Pending FDA Input Phase 3 study for patients with ER+ / Additional potential indications based on HER2- mBC who progressed on CDK4/6 POC and nonclinical study data therapy ▪ Combining gedatolisib with endocrine therapies o Goal is to begin enrollment of Phase 3 clinical in
Slide 17: Review of Preliminary Phase 1b Data
Review of Preliminary Phase 1b Data As of January 11, 2021 data cut-off 17
Slide 18: 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 ER and CDKi treatment Treatment Strategy o Simultaneously blocking interdependent ER, PI3K, mTOR & CDK signaling pathways in ER+ breast cancer addresses ER and CDKi resistance mechanisms o Inhi
Slide 19: B2151009: Phase 1b Study (138 patients)
B2151009: Phase 1b Study (138 patients) Dose escalation and safety/efficacy expansion (early signals of clinical activity) 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 May 20
Slide 20: 60% of Patients Achieved an Objective Response
60% of Patients Achieved an Objective Response Minimal correlation between PIK3CA status (mutant or WT) and response Tumor Size Change Data (Number of Subjects – 88) ORR1 = 60% (53/88) Source: (1) ORR includes 5 Unconfirmed PR; Note: PR* is an unconfirmed PR Note: Data presented is from a preliminar
Slide 21: Palbociclib + Endocrine Therapy + / - Gedatolisib
Palbociclib + Endocrine Therapy1 + / - Gedatolisib 1L 1L+ 2L 2L/3L Patients o Primary objective of B2151009 expansion CDKi-naïve CDKi-naïve CDKi-naïve Prior CDKi portion (Arms A, B, C, D) was to Evaluable Patients N=3382 N=243 N=2674 N=125 N=257 determine if addition of gedatolisib to palbociclib +
Slide 22: 2L/3L Gedatolisib + Palbociclib + Fulvestrant vs. 2L SOC
2L/3L Gedatolisib + Palbociclib + Fulvestrant vs. 2L SOC CDKi Status CDKi-naïve Prior CDKi Evaluable Patients N=1261 N=4852 N=1361 N=1003 N=254 Gedatolisib + Alpelisib + Exemestane + Alpelisib + Palbociclib + Study Treatment Fulvestrant Fulvestrant Everolimus Fulvestrant Fulvestrant (G+P+F) PIK3CA S
Slide 23: Gedatolisib combinations vs. SOC Benchmarks for ER+/HER2- mBC
Gedatolisib combinations vs. SOC Benchmarks for ER+ / HER2- mBC Biggest unmet need is in the 2nd line setting where Gilroy combo has most differentiation Indication Drug Regimen Efficacy 1st/2nd Line ER+/HER2- Metastatic PFS 11.9 months, ORR 75% Gedatolisib + Palbo + Fulvestrant1 May have received p
Slide 24: Safety Summary: Treatment-Emergent Adverse Events
Safety Summary: Treatment-Emergent Adverse Events Single Agent gedatolisib and gedatolisib + palbociclib + ET Phase 1 Trial: Gedatolisib alone Phase 1b Trial: G + P + ET Phase 1b Trial: G + P + ET (154 mg weekly IV) (180 mg IV, once weekly or 3 weeks, one week off) o Combo has been well tolerated Al
Slide 25: Gedatolisib Opportunity in HER2+/PIK3CA+ mBC Patients
Gedatolisib Opportunity in HER2+/PIK3CA+ mBC Patients Patients received 3 or more lines of prior HER2 therapies o Aberrant PI3K/mTOR is a known HER-2+ MBC who Until progression progressed after 3 or Herzuma + resistance mechanism of HER2 Intolerable toxicity more HER-2 directed Gedatolisib Patients’
Slide 26: 56% ORR for Patients Receiving Gedatolisib + Trastuzumab Biosimilar
56% ORR for Patients Receiving Gedatolisib + Trastuzumab Biosimilar Best Response Duration of Response *Patient whose target lesion decreased by 63% but a new leptomeningeal seeding occurred. o 9 of 16 (56%) showed partial response (PR) Swimmer plot of the treatment duration o 4 of 16 (25%) had stab
Slide 27: Experienced drug development team
Experienced drug development team CMO SVP R&D VP Clin Dev VP Clin Ops Head CMC Art DeCillis, MD John MacDonald, PhD Igor Gorbatchevsky, MD Jill Krause Bernhard Lambert, PhD CMO for Eleven Biotherapeutics SVP R&D at MGI Pharma 17% VP Clinical Dev at MEI Pharma VP Clinical Operations Quality Executive
Slide 28: 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. Filip Janku M.D., Ph.D. Clinical Advisory Board Hung Khong M.D. Bora Lim M.D. Mothaffar Rimawi M.D. Alberto Montero M.D. Lee Schwartzberg M.D. Scientific Ad
Slide 29: Celcuity Leadership Team
Celcuity Leadership Team Co-Founder and CEO Co-Founder and CSO CFO CBO Brian Sullivan Lance Laing, PhD Vicky Hahne Eric Lindquist CEO, Founder - PUR Water Scientist at Scriptgen/Anadys CFO – SimonDelivers (on-line 17% Global VP of BD at Natera Filters (purchased by Novartis) grocery) (Signatera) o S
Slide 30: Summary – Strategic Overview
Summary – Strategic Overview Proprietary Gedatolisib Experienced Financial CELsignia Technology In-licensed Team Resources CELsignia can identify Preliminary results from Experienced clinical team Approximately $44 million new indications for phase 1b clinical trial with successful track cash on han
Slide 31: 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 31
Slide 32: 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 33: 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 34: 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 35: 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 cause Drug resistance mechanisms (e.g. HER2+) not required for oncogenic signaling characterized oncogenic signali
Slide 36: CELsignia CDx identifies new patients for targeted therapies
CELsignia CDx identifies new patients for targeted therapies Pharma Pathway Targets Targeted Therapies Unique Patient Pool Impact Genentech Pfizer HER2 Herceptin $4B1 Perjeta Tepotinib available market Roche PI3K Nerlynx Piqray for Celcuity Merck c-MET 2x more Tepmetko Tafinlar Novartis MEK Aliqopa
Slide 37: Celcuity is a clinical stage biotechnology company
Celcuity is a clinical Our third-generation cellular stage biotechnology analysis platform unravels complex oncogenic activity company that molecular tests can’t detect. discovers previously undetectable cancer We harvest these insights to drivers and develops develop new targeted therapies drugs to