Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (October 2023)
43 slides from Purple Biotech's investor presentation, Oct 13, 2023
Slide 1: Corporate Presentation October 2023
| 1 NASDAQ/TASE: PPBT October 2023 CORPORATE PRESENTATION
Slide 2: Forward-looking Statements and Safe Harbor
| 2 Forward - looking Statements and Safe Harbor Certain statements in this press release 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
Slide 3: Corporate Highlights
| 3 Corporate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of June 30, 2023 • ADS Outstanding: 21.4 M • Cash Balance : $18 M Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2023 & 2024 • Two First - in - Class clinical st
Slide 4: Leadership Team
| 4 Leadership Team Hadas Reuveni, PhD VP Research & Development Formerly at Keryx (NASDAQ:KERX) Michael Schickler, PhD Head of Clinical and Regulatory Affairs Formerly at Hoffmann - La Roche, CEO at CureTech Gil Efron Chief Executive Officer Former Deputy CEO & CFO at Kamada (NASDAQ:KMDA) Fabien Se
Slide 5: A Pipeline Dedicated to Advancing Oncology Therapies
| 5 A Pipeline Dedicated to Advancing Oncology Therapies *Clinical collaboration and supply agreement with: Multiple data read - outs expected in the next 12 months Value Drivers Development Stage Indications Target Project Phase III Phase II Phase I Pre - Clinical □ Phase 2 interim analysis 2 H 23
Slide 6: Advancing First-in-Class Oncology Therapies: CM24
Advancing First - in - Class Oncology Therapies CM 24 : an α - CEACAM 1 * mAb Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC) *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 7: CM24: a New Multi-Functional Immune Checkpoint Inhibitor
| 7 CM 24 : a New Multi - Functional Immune Checkpoint Inhibitor • CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells • CEACAM1 interacts with CEACAM1 and CEACAM5 and creates a tumor - protective environment Attractive new target • C M24 increases T cell and NK cells cytot
Slide 8: CM24 MOA
| 8 CM24 MOA | Immune Check Point Inhibitor & Anti - Metastatic Activity 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 R
Slide 9: CEACAM1 is Over-Expressed in Pancreatic Cancer
| 9 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 Pancreatic Cancer
Slide 10: Large Market Opportunity in Pancreatic Cancer
| 10 Large Market Opportunity in Pancreatic Cancer • Pancreatic Cancer accounts for ~60K new cases/year in the US alone; with a 5 - year relative survival rate of 11.5% 1 • Immuno - oncology approaches have been limited to patients with high microsatellite instability (MSI - H) or high tumor mutatio
Slide 11: CM24 Phase 1 Dose Escalation Results
| 11 CM24 Phase 1 Dose Escalation Results E ncouraging data in 2L/3L Pancreatic Ductal Adenocarcinoma (PDAC) patients Study Results 14 patients were evaluable for efficacy: • Best overall response included 1 Partial Response (PR) (PDAC) and 4 Stable Disease (SD) ( 3 PDAC and 1 papillary thyroid canc
Slide 12: Phase 1 study results: exploratory biomarkers
| 12 Phase 1 study results (cont.): Identification of potential exploratory biomarkers supporting CM24’s mechanism of action Higher pre - treatment level s of tumor infiltrating lymphocytes that express CEACAM 1 are associated with longer s urvival • consistent with the CM 24 MoA in suppressing the
Slide 13: CM24 Combination Study with Nivolumab plus Chemotherapy in PDAC
| 13 A study of CM 24 in combination with nivolumab plus chemotherapy in PDAC patients in 2 L treatment 18 centers are currently active in US, EU & Israel Measurement of CEACAM1 and other bio - markers is ongoing 2023 2024 Primary endpoint : OS Secondary endpoints: PFS, OS rate @ 6 & 12 months, PFS
Slide 14: Advancing First-in-Class Oncology Therapies: NT219
Advancing First - in - Class Oncology Therapies NT 219 : A Small Molecule Dual Inhibitor of IRS 1 / 2 and STAT 3 Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)
Slide 15: NT219, a new solution to improve treatment outcome
| 15 NT219, a new solution to improve treatment outcome for cancer patients Confidential • 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 • Uniquely positioned to tackle
Slide 16: NT219 blocks critical signalling pathways at once
| 16 NT 219 blocks 2 critical signalling pathways at once IRS 1 / 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/E
Slide 17: Strong Efficacy in Monotherapy
| 17 Animal model Head & Neck Cancer (SCC - 9) NSG Ρ , immuno - competent Drugs α - PD 1 Cetuximab NT 219 Strong Efficacy in Monotherapy • NSG mice were injected SC with SCC - 9 cells . • PBMCs (18*10 6 cells per mouse) administered 4 weeks prior to first treatment . • NT219 (IV), α - PD1 (IP), and
Slide 18: NT219 Restores Sensitivity to EGFRi in PDX Models
| 18 NT 219 Restores Sensitivity to EGFRi in PDX Models Lung Cancer Non - small cell lung cancer (NSCLC) Exon 19 deletion EGFR and T790M, biopsy of bone marrow metastasis, patient previously progressed on afatinib and osimertinib Head & Neck Cancer Recurrent/metastatic squamous cell carcinoma of the
Slide 19: First Market Opportunity: Recurrent or Metastatic SCCHN
| 19 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,8 major global
Slide 20: NT219 Monotherapy and Combination Phase 1/2 Study Design
| 20 NT 219 Monotherapy and Combination Phase 1 / 2 Study Design ( NCT 04474470 ) Study Title A Phase 1 / 2 study with open - label, dose escalation p hase followed by single - arm expansion to assess the safety, tolerability, PK, PD and efficacy of NT 219 , alone in adults with recurrent or metasta
Slide 21: Phase 1 dose escalation in combination with cetuximab
| 21 Phase 1 dose escalation in combination with cetuximab: Combination is well tolerated, target exposure reached • No DLTs reported, NT 219 was well tolerated as monotherapy and in combination with cetuximab • Dose - dependent increase in AUC and Cmax values • Human Equivalent Dose exposure was re
Slide 22: Efficacy overview of monotherapy and combination arms
| 22 Efficacy overview of m onotherapy arm *: • 20 evaluable patients (all doses): • 2 PR (confirmed - GEJ, unconfirmed - PDAC). • 5 SD Efficacy overview of combination arm in SCCHN patients * : • 12 evaluable patients (all doses) : • 2 confirmed PR @ 50 mg/kg • 3 SD @ 6 and 12 mg/kg • DCR: 46 % In
Slide 23: IM1240: CD3x5T4xNKG2A Conditionally-Activated Tri-Specific Antibody
Advancing First - in - Class Oncology Therapies IM1240: CD3x5T4xNKG2A Conditionally - Activated Tri - Specific Antibody
Slide 24: A Novel Mechanism of Action: Tri-Specific Antibody Activated in TME
| 24 A Novel Mechanism of Action Tri - Specific Antibody Engagement Activated in TME Masked pre - form Cancer binder a - TAA Abs a - NK binder Abs T - cell - binder a - CD3 Abs aCD 3 masking moiety Tumor cell T cell NK cell Cancer microenvironment Protease cleavage Removal of T cell engager ’ s mask
Slide 25: 5T4, a Novel Target in Oncology
| 25 5 T 4 , a Novel Target in Oncology 5 T 4 is highly expressed on certain tumors and correlates with poor prognosis Am J Cancer Res 2018 ; 8 ( 4 ): 610 - 623 www.ajcr.us /ISSN: 2156 - 6976 /ajcr 0074519 5 T 4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of pati
Slide 26: Promising Proof of Concept Data
| 26 Promising Proof of Concept Data • Tribody induces sub - nM EC 50 against A 549 cells • 20 - fold more potent than CD 3 x 5 T 4 variant • Cell killing validated on multiple 5 T 4 + cell lines (MDA - MB - 231 , HCT 116 , NCI - H 226 ) • Sustained regressions in Breast Cancer xenograft model ( MDA
Slide 27: Corporate Highlights
| 27 Corporate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of June 30 , 2023 • ADS Outstanding: 21.4 M • Cash Balance : $ 18 M Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2023 & 2024 • Two First - in - Class clinical
Slide 28: Contact Us / Thank You
| 28 Contact Us: ir@purple - biotech.com THANK YOU
Slide 29: Appendix A: CM24
Appendix A | CM 24
Slide 30: CEACAM Plays a Key Role in Cancer Biology
| 30 CEACAM 1 Plays a Key Role in Cancer Biology 01 | ADHESION Horst, 2011 “ CEACAM 1 creates a pro - angiogenic tumor microenvironment that supports tumor vessel maturation ” “ Neutrophil extracellular trap - associated CEACAM 1 as a putative therapeutic target to prevent metastatic progression of
Slide 31: CM24 Reduces Tumor Burden & Synergetic with α-PD-1
| 31 CM 24 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 2
Slide 32: Phase 1 Dose Escalation Interim Results: Safety with Nivolumab
| 32 Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combi na tion with Nivolumab Grade Total AE Term 4/5 3 2 1 1 4 5 Diarrhea 3 1 4 Abdominal pain 2 2 4 Fever 1 3 4 Headache 4 4 Fatigue 2 1 3 Nausea 1 2 3 Creatinine increased 2 2 Hypokalemia 1 1 2 Dyspnea 2 2 Constipation
Slide 33: CM24 Phase 1 Combination Study Demographics
| 33 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 34: Confirmed Partial Response in a 3L PDAC Patient
| 34 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 35: Appendix B: NT219
Appendix B | NT219
Slide 36: Novel MOA: IRS Degradation by NT219
| 36 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 37: NT219 Re-sensitizes Tumors Refractory to α-PD1
| 37 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 38: Novel MOA: STAT3 Inhibition
| 38 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 39: Simultaneous Blockade of STAT and AKT Pathways
| 39 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 40: Selected Publications
| 40 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 41: NT219 Suppresses β-Catenin Activity in CRC Cells
| 41 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 IRS 2 demonstrate enhanced b - catenin activity. Targeted inhibition o
Slide 42: Pancreatic Cancer in Combination with Gemcitabine
| 42 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® ) NT 219 | Pancreatic Cancer in Combination with Gemcitabine Highly effective anti cancer activity exhibited by NT 219 in combination with Gemcitabine
Slide 43: RNA Sequencing Analysis of Tumors Following Treatment
| 43 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ®) RNA Sequencing | Analysis of Tumors Following Treatment Reduced expression of IRS 1 , Ki 67 , FOXM 1 & TGFb is exhibited by pancreatic cancer treated with NT 219 alone and in combination with gemcitabine
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