Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (November 2022)
41 slides from Purple Biotech's investor presentation, Nov 9, 2022
Slide 1: Corporate Presentation November 2022
| 1 NASDAQ/TASE: PPBT November 2022 CORPORATE PRESENTATION
Slide 2: Forward-looking Statements and Safe Harbor
| 2 Forward - looking Statements and Safe Harbor Certain statements in this presentation that are forward - looking and not statements of historical fact are forward - looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . Such f
Slide 3: Business Highlights
| 3 Business Highlights Strong balance sheet and cash position Purple Biotech (NASDAQ/TASE: PPBT) $35.7M cash as of September 30, 2022 ADSs outstanding: 18.4M Multiple data read - outs expected in the next 12 months • Two first - in - class clinical stage drugs • Multiple Phase II studies ongoing an
Slide 4: Harnessing the Power of the TME
| 4 Harnessing the Power of the TME • Hammering cancer cells is not sufficient ( i.e , chemotherapy, radiotherapy) • Tumors rely on a favorable environment to strive and escape the Immune surveillance • Multiple resistance mechanisms prevent long - term survival • Concept fully validated with the ri
Slide 5: A Pipeline Dedicated to Advancing Oncology Therapies
| 5 Program Indication Phase 1 Phase 2 Phase 3 Value Drivers CM24 (CEACAM - 1) S olid tumors (monotherapy) √ RP2D in combination: 20 mg/kg √ Initiation of phase II in 2L PDAC Follow up OS data from P1 Interim analysis P2 2H23 Top line P2 2H24 Investigation in a second indication S olid tumors (combi
Slide 6: CM24: an α-CEACAM1 mAb
Advancing First - in - Class Oncology Therapies CM24: an α - CEACAM1* mAb *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 7: CM24: a New Multi-Functional Immune Checkpoint Inhibitor
| 7 CM24: a New Multi - Functional Immune Checkpoint Inhibitor • CEACAM 1 is overexpressed on certain tumor cells and infiltrating immune cells • CEACAM 1 interacts with CEACAM 1 and CEACAM 5 and creates a tumor - protective environment Attractive new target • CM24 inhibits the immunosuppressive eff
Slide 8: CEACAM1 Plays a Key Role in Cancer Biology
| 8 CEACAM1 Plays a Key Role in Cancer Biology 01 | ADHESION Horst, 2011 “ CEACAM1 creates a pro - angiogenic tumor microenvironment that supports tumor vessel maturation ” “ Neutrophil extracellular trap - associated CEACAM1 as a putative therapeutic target to prevent metastatic progression of colo
Slide 9: CM24 MOA
| 9 CM24 MOA | Immuno - Oncology & Adhesion Markel et al, J Immunol 2002, 2006; Immunology, 2008; Cancer Immunol Immunother 2010; Ortenberg et al, Mol Cancer Ther 2012; Zhou, 2009; Li, 2013; Huang, 2015; Acharya N, et al. J Immunotherapy Canc 8:e911 - 22, 2020. ; Rayes RF, et al. Neutrophil Extracel
Slide 10: CM24 Reduces Tumor Burden & Synergetic with α-PD-1
| 10 CM24 Reduces Tumor Burden & Synergetic with α - PD - 1 Xenograft, lung lesion melanoma model (Mel 526, IV), 7 mice/group (NOD/SCID), 4 TIL injections IV, every 10 days, Ab Dose: 10 mg/kg, Ab Regimen: twice a week, study duration 70 days (last treatment day – 44), tumor burden was monitored 26 d
Slide 11: CEACAM1 is Over-Expressed in PDAC
| 11 Representative examples of CEACAM1 immunohistochemical images of pancreatic adenocarcinoma and normal tissues Comparison between CEACAM 1 staining intensity in pancreatic cancer ( 38 cases/ 76 cores) and normal ( 10 cases/ 20 cores) tissues CEACAM1 is Over - Expressed in PDAC
Slide 12: CM24 Phase 1 Dose Escalation Interim Results: Safety
| 12 Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combi na tion with Nivolumab AE Term Total Grade 1 2 3 4/5 Diarrhea 5 4 1 Abdominal pain 4 1 3 Fever 4 2 2 Headache 4 3 1 Fatigue 4 4 Nausea 3 1 2 Creatinine increased 3 2 1 Hypokalemia 2 2 Dyspnea 2 1 1 Constipation 2 2
Slide 13: Sustained Clinical Benefit Even After Treatment Cessation
| 13 CM24 Phase 1 Dose Escalation Interim Results (cont.) Sustained Clinical Benefit Even After Treatment Cessation For the 11 evaluable patients as of March 8th, 2022, best overall response included 1 confirmed PR (PDAC patient ) 3 SD (2 PDAC and 1 PTC) for a disease control rate of 36% • 9/11 of t
Slide 14: Confirmed Partial Response in a 3L PDAC Patient
| 14 Confirmed Partial Response in a 3L PDAC Patient Patient Profile • 65 y/o female, pancreatic cancer • 2 prior lines of treatments: FOLFIRINOX and gemcitabine/nab - paclitaxel • Post Whipple Procedure • Patient had a germline NF1 VUS, with MSI - S and PDL - 1 IHC 2+ and 5% staining • Confirmed Pa
Slide 15: Large Market Opportunity in Pancreatic Cancer
| 15 Large Market Opportunity in Pancreatic Cancer • Pancreatic Cancer accounts for ~60K new cases/year in the US; with a 5 - year relative survival rate of 11.5% 1 • I/O approaches have been limited to patients with high microsatellite instability (MSI - H) or high tumor mutational burden (TMB - H
Slide 16: CM24 Phase 2 Combination Study Design
| 16 A study of CM24 in combination with nivolumab plus chemotherapy in PDAC patients in 2L 11 centers are currently active in US, EU & Israel Measurement of CEACAM1 and other bio - markers is ongoing Planning of further studies in other tumor types is ongoing 2022 2023 2022 2023 2024 Primary effica
Slide 17: NT219: A Small Molecule Dual Inhibitor of IRS1/2 and STAT3
Advancing First - in - Class Oncology Therapies NT219: A Small Molecule Dual Inhibitor of IRS 1/2 and STAT3
Slide 18: NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond
| 18 NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond • NT219 is a First - in - Class , small molecule • Dual inhibitor of IRS1/2 and STAT3 Innovative MOA • Outstanding efficacy in various PDX models in monotherapy and in combination • Modulation of the tumor microenvironment • Un
Slide 19: NT219 - Dual Inhibitor of IRS1/2 & STAT3
| 19 NT219 - Dual Inhibitor of IRS1/2 & STAT3 NT219 IRS1/2 • Scaffold proteins, mediating mitogenic, metastatic, angiogenic and anti - apoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumors • Regulates major survival pathways such as the PI3K/AKT, MEK/ERK and WN
Slide 20: Novel MOA: IRS Degradation By NT219
| 20 Novel MOA: IRS Degradation By NT219 Blocking IGF1R - AKT Pathway 1 Binding to IRS 1 1 Reuveni et al. Cancer Res 2013 ; Ibuki et al. Mol Cancer Ther 2014 Ser - phosphorylation 2 Degradation 3 Covalent binding to IRS1/2 leads to the dissociation of IRS1/2 from IGF1R Serine phosphorylation prevent
Slide 21: Novel MOA: STAT3 Inhibition
| 21 Novel MOA Signal Transducer and Activator of Transcription 3 ( STAT 3 ) Inhibition • Point of convergence for numerous oncogenic signaling pathways • Central in regulating the anti - tumor immune response • Broadly hyperactivated both in cancer and non - cancerous cells within the tumor ecosyst
Slide 22: Simultaneous Blockade of STAT and AKT Pathways Required to Overcome Resistance
| 22 Simultaneous Blockade of STAT 3 and AKT Pathways are Required to Overcome Resistance to EGFRi Overcoming drug resistance NT 219 NT 219 STAT 3 IRS EGFR EGFRi MEK / ERK TUMOR REGRESSION Proof of Concept: PDX model of Head and Neck Cancer Erlotinib+Ruxolitinib (n= 6 ) Erlotinib+Buparlisib (n= 6 )
Slide 23: NT219 is Effective as Monotherapy
| 23 NT 219 is Effective as Monotherapy Animal Model Head & Neck Cancer (SCC - 9 ) NSG Ρ , PBMCs - injected 1 Drugs α - PD 1 Cetuximab (Erbitux®) NT 219 20 mg/kg NT 219 60 mg/kg 1 NSG mice were injected SC with SCC - 9 cells . PBMCs were injected to the mice ( 18 M cells per mouse) and treatments in
Slide 24: NT219 Restores Sensitivity to EGFRi in PDX Models
| 24 Treatments on days 0 , 3 and 10 , cetuximab - 1 mg/mouse, 3 mice/group; PBMCs ( 1.4 M cells/mouse) were injected on day 6 Osimertinib 5 mg/kg, NT 219 65 mg/kg, mean tumor volume at the end point, 3 mice/group; 0 500 1,000 1,500 2,000 Control NT219 Osimertinib Osimertinib+NT219 Tumor Volume (mm
Slide 25: NT219 Re-Sensitizes Tumors Refractory to α-PD-1
| 25 0 200 400 600 800 1000 1200 0 5 10 15 20 Tumor volume (mm 3 ) Days following treatment initiation Control (n=3) NT219 (n=3) Keytruda (n=3) Keytruda + NT219 (n=3) Autologous PBMCs ( 2.1 M/mouse) NT 219 Re - sensitizes Tumors Refractory to α - PD 1 PDX Model Humanized PDX of GastroEsophageal Junc
Slide 26: NT219 Phase 1 Dose Escalation Monotherapy Interim Results
| 26 NT219 Phase 1 Dose Escalation Monotherapy Interim Results Study Design • As of data cutoff date of May 12 th , 2022, a total of 14 patients were enrolled and 12 patients were evaluable for DLT determination (4 CRC, 3 pancreatic cancer, 2 breast cancer, 1 GEJ, 1 esophageal, and 1 appendiceal can
Slide 27: Encouraging Initial Efficacy Signals
| 27 NT219 Phase 1 Dose Escalation Monotherapy Interim Results: Encouraging Initial Efficacy Signals • For the 12 evaluable patients, best overall response included one confirmed PR (GEJ patient, > 5.5 months duration of response following end of treatment), and 3 SD with one patient awaiting follow
Slide 28: Confirmed PR as Single Agent in a GEJ Cancer Patient
| 28 Confirmed PR as Single Agent in a GEJ Cancer Patient • In a patient with refractory GE junction disease (mutated KRAS, TP53), NT219 administration ( 3mg/kg as a single a gent ) was associated with a confirmed partial response (PR): • Complete remission at the largest target lesion (right) • Com
Slide 29: First Market Opportunity: R/M SCCHN
| 29 First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Global Data 2018: Head and Neck Squamous Cell Carcinoma: Opportunity Analysis and Forecasts to 2026 ; Internal best current e sti mates of patient numbers based on external research, 5 major global
Slide 30: NT219 Monotherapy and Combination Phase 1/2 Study Design
| 30 NT 219 Monotherapy and Combination Phase 1 / 2 Study Design ( NCT 04474470 ) Study Title A phase 1 / 2 study with open - label, dose escalation phase followed by single - arm expansion to assess the safety, tolerability, PK, PD and efficacy of NT 219 , alone in adults with recurrent or metastat
Slide 31: Business Highlights
| 31 Business Highlights Strong balance sheet and cash position Purple Biotech (NASDAQ/TASE: PPBT) $35.7M cash as of September 30, 2022 ADSs outstanding: 18.4 M Multiple data read - outs expected in the next 12 months • Two first - in - class clinical stage drugs • Multiple Phase II studies ongoing
Slide 32: Thank You
| 32 We are committed to provide cancer patients with first - in - class therapies to OVERCOME tumor drug resistance, ENHANCE treatment response and SLOW tumor progression Contact Us: ir@purple - biotech.com THANK YOU
Slide 33: Appendix A | CM24
Appendix A | CM24
Slide 34: PK/PD Modeling Provides Dosage & Schedule Guidance
| 34 PK/PD Modeling Provides Dosage & Schedule Guidance Simulated TMDD 1 saturation at Ctrough 2 with Q2W regimen • CM 24 completed Phase 1 monotherapy open - label, dose - escalation study to assess safety and tolerability • Heavily pre - treated 24 evaluable patients with a median of 4 prior regim
Slide 35: CM24 Phase 1 Combination Study Demographics
| 35 CM24 Phase 1 Combination Study (NCT04731467) Demographics In the Phase 1 part, patients with indicated refractory cancers were administered CM24 at 10, 15, and 20mg/kg q2w and nivolumab 480mg q4w. • The primary objective of this part was to evaluate safety, tolerability, pharmacokinetics and de
Slide 36: Appendix B | NT219
Appendix B | NT219
Slide 37: Selected Publications
| 37 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 38: NT219 Suppresses β-Catenin Activity in CRC Cells and Inhibits Brain Metastasis
| 38 AACR Annual Meeting, April 2021, AACR Virtual Special Conference on Epigenetics and Metabolism, Oct 2020, Ido Wolf, MD, Head of Oncology Division, Tel Aviv Sourasky Medical Center Colon cancer LS - 513 cells overexpressing IRS2 demonstrate enhanced b - catenin activity. Targeted inhibition of I
Slide 39: NT219 in Combination with Gemcitabine in Pancreatic Cancer
| 39 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® ) NT219 | Pancreatic Cancer in Combination with Gemcitabine Highly effective anti cancer activity exhibited by NT219 in combination with Gemcitabine
Slide 40: RNA Sequencing Analysis of Tumors Following Treatment
| 40 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ®) RNA Sequencing | Analysis of Tumors Following Treatment Reduced expression of IRS1, Ki67, FOXM1 & TGFb is exhibited by pancreatic cancer treated with NT219 alone and in combination with gemcitabine
Slide 41: NT219 Phase 1 Dose Escalation Monotherapy Demographics
| 41 NT219 Phase 1 Dose Escalation Monotherapy Demographics As of data cutoff date of May 12th , 2022, a total of 14 patients were enrolled to 4 NT219 dose levels (3 - 24mg/kg) • 12 patients were evaluable for DLT determination including 4 CRC, 3 pancreatic cancer, 2 breast cancer, and one of each o
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