Purple Biotech Ltd. · TASE:PPBT

Purple Biotech — Investor Presentation (July 2024)

53 slides from Purple Biotech's investor presentation, July 2024

  1. Slide 1: Corporate Presentation

    CORPORATE PRESENTATION NASDAQ/TASE: PPBT July 2024 |1

  2. Slide 2: Forward-looking Statements and Safe Harbor

    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 forward-look

  3. Slide 3: Corporate highlights

    Corporate highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Multiple data read-outs expected in 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of March 31, 2024 • A preclinical tri-speci

  4. Slide 4: A pipeline dedicated to advancing oncology therapies

    A pipeline dedicated to advancing oncology therapies Project Target Indications Development Stage Value Drivers Pre-Clinical Phase I Phase II Phase III ❖ Phase 2 interim CEACAM1 Pancreatic Cancer analysis 2H24 CM24 mAb (+nivolumab*+SoC) ❖ Phase 2 top line results 2H24 Solid tumors (monotherapy) STAT

  5. Slide 5: CM24: an α-CEACAM1 mAb

    Advancing First-in-Class Oncology Therapies CM24: an α-CEACAM1* mAb Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC) *Carcinoembryonic Antigen Cell Adhesion Molecule

  6. Slide 6: CM24: a new multi-functional CEACAM1 inhibitor

    CM24: a new multi-functional CEACAM1 inhibitor Attractive • CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells new target • CEACAM1 is a part of the Neutrophil Extracellular Traps (NETs) structure • CM24 increases T cell and NK cells-mediated cytotoxicity against tumors De

  7. Slide 7: CM24 MOA (#1) Immune check point inhibitor

    CM24 MOA (#1) Immune check point inhibitor Anti tumor immune response CEACAM1 expression on tumor and tumor-infiltrating immune cells in PDAC activation Tumor Normal PDAC tumor cells Immune cells CEACAM1 CEACAM5 CM24 CD CEACAM1+ CD8+ 80µ 80µ m m CEACAM1 CEACAM1 CD CEACAM1+NK cells 80µ 80µ m m Repres

  8. Slide 8: CM24 MOA (#2) Blocks NET oncogenic potential

    CM24 MOA (#2) Blocks NET oncogenic potential thru CEACAM1 blockage • Neutrophil extracellular traps (NETs) are web-like structures involved in: ➢ Tumor immune evasion (1, 3) CM24 ➢ Tumor progression (1, 2, 6) CCAM1 ➢ Metastasis (2, 3, 5, 6) CCAM1 CM24 ➢ Cancer-associated thrombosis (4) CM24 • CEACAM

  9. Slide 9: CM24 MOA (#2 cont.)

    CM24 MOA (#2 cont.) Blocks NET oncogenic potential thru CEACAM1 blockage CM24 binds to CEACAM1 on NETs CM24 Inhibits NET-Induced CM24-Nivo treatment significantly reduced the migration of CEACAM1 expressing enhanced NET levels in patient’s serum cancer cells Level of MPO in patient serum (% of Pre-t

  10. Slide 10: Large Market Opportunity in Pancreatic Cancer

    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 12%1 • Immuno-oncology approaches have been limited to patients with high microsatellite instability (MSI-H) or high tumor mutational burden (TM

  11. Slide 11: Phase 2 Combination Study Design (NCT04731467)

    Phase 2 Combination Study Design (NCT04731467) A study of CM24 in combination Primary endpoint : Additional Interim Measurement of with nivolumab plus OS analysis: 2H24 CEACAM1 and chemotherapy in patients with Top line data: 2H24 other bio-markers Secondary endpoints: PDAC in the 2nd line is ongoin

  12. Slide 12: Phase 2 interim data (cut off date - May 8, 2024)

    Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal/IRI/5FU/LV sub-study Characteristic Experimental Control • 31 PDAC patients were randomized to the Nal- (n=16) (n=15) IRI/5FU/LV- based study regimen with a median Age (median) 66 68 Age ≥65 (n, %) 8 (50.0) 11 (73.3) follow up of 8

  13. Slide 13: Phase 2 interim data (cut off date - May 8, 2024)

    Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal-IRI/5FU/LV sub-study ➢ 26% reduction in risk of death (HR=0.74) and 28% reduction in the risk of progression or death (HR=0.72) ➢ Prolongation of 2.1 months in median overall survival and 1.9 months in median progression-free survi

  14. Slide 14: Phase 2 interim data (cut off date - May 8, 2024)

    Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal-IRI/5FU/LV sub-study ➢ Higher objective response rate (ORR) (25% vs 7%) ➢ Higher disease control rate (DCR) (63% vs 40%) ➢ Consistent and continuous decrease in CA19-9 was observed % change in tumor size Median CA 19-9 levels | 14

  15. Slide 15: Phase 2 interim data: Efficacy summary

    Phase 2 interim data (cut off date - May 8, 2024) Efficacy summary Parameter Experimental (n=16) Control (n=15) OS (mo, median; 95% CI) 7.72 (4.00-8.11) 5.62 (3.22 -7.89) OS HR (95% CI) 0.74 (0.31-1.77) 6 mo OS (%) 52.7 38.9 PFS (mo, median; 95% CI) 3.8 (1.8-5.0) 1.9 (0.9-3.6) PFS HR (95% CI) 0.72 (

  16. Slide 16: Interim biomarker analysis

    Interim biomarker analysis NET’s marker as a potential predictive biomarker Phase 2 CM24+nivolumab+Nal-IRI/5FU/LV sub-study interim analysis: • NET-related serum MPO levels: ➢ Enhanced levels were measured in >90% of the patients ➢ NET-related mean MPO over 6-fold higher than healthy donors. • Pre-d

  17. Slide 17: NT219: A Small Molecule Dual Inhibitor of IRS 1/2 and STAT3

    Advancing First-in-Class Oncology Therapies NT219: A Small Molecule Dual Inhibitor of IRS 1/2 and STAT3 Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)

  18. Slide 18: NT219, a new solution to improve treatment outcome for cancer patients

    NT219, a new solution to improve treatment outcome for cancer patients • NT219 is a First-in-Class, small molecule dual inhibitor of IRS1/2 and STAT3 Innovative • Covalently binds to IRS1/2 and leads to their degradation MOA • Affects both the tumor and the TME • Suppresses cancer stem cells Robust

  19. Slide 19: NT219 blocks 2 critical signalling pathways at once

    NT219 blocks 2 critical signalling pathways at once IRS1/2 • Scaffold proteins, mediating mitogenic, metastatic, angiogenic and anti- apoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in STAT3 multiple tumors • Well-established transcription factor • Regulates major survival

  20. Slide 20: NT219 restores sensitivity to EGFRi in PDX models

    * Tumor Volume (mm3) 2,000 NT219 restores 1,500 sensitivity to EGFRi 1,000 in PDX models 500 0 Lung Cancer Control NT219 Osimertinib Osimertinib+NT219 Osimertinib 5 mg/kg, NT219 65 mg/kg, mean tumor volume at the end point, 3 mice/group; Non-small cell lung cancer (NSCLC) Exon 19 deletion EGFR and T

  21. Slide 21: NT219 re-sensitizes PD1-refractory model

    NT219 re-sensitizes PD1-refractory model NT219+PD1 reverse resistant tumors NT219 induces PDL1 expression 2000 Control (n=10) Control α-PD-1 (n=10) PD1-resistant melanoma α-PD-1 NT219 (n=10) cells (FACS analysis) Tumor volume (mm3) NT219 1500 NT219+α-PD-1 (n=10) NT219+α-PD-1 ✱✱✱✱ PDL1 expression

  22. Slide 22: NT219 combination with αPD1 reprograms the TME

    NT219 combination with αPD1 achieves a profound reprograming of the TME NT219+PD1 leads to a significant increase in NT219+PD1 leads to a significant reduction in cytotoxic effector cells (T & NK cells) myeloid derived suppressor cells (MDSC) cells (% CD8+GZMB +) Activated cytotoxic T (out of CD45

  23. Slide 23: First Market Opportunity

    First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Targeting the unmet medical need • SCCHN is the 6th most common cancer type ; 175k new cases/year are expected by 2024 • 1L standard of care has shifted from chemotherapy towards immuno-oncology + chemo

  24. Slide 24: Phase 1 dose escalation in combination with cetuximab

    Phase 1 dose escalation in combination with cetuximab: Well tolerated, target exposure reached, patient’s responses observed • No DLTs reported, NT219 was well tolerated as monotherapy and in combination with cetuximab • Dose-proportional increase in AUC and Cmax values • Human Equivalent Dose expos

  25. Slide 25: Phase 1 Dose Escalation: Anti-tumor activity at target exposure

    Phase 1 Dose Escalation (cont.): Anti-tumor activity at target exposure level, 2 confirmed responses in SCCHN patients Efficacy overview of monotherapy arm: • 20 evaluable patients (all doses): 2 PR (confirmed-GEJ, unconfirmed-PDAC), 5 SD Best % change from baseline Efficacy overview of combination

  26. Slide 26: Activated IGF1R and STAT3 as potential predictive biomarkers

    Activated IGF1R and STAT3 as potential predictive biomarkers Biomarker analysis at the 50mg/kg dose of NT219 with cetuximab: • Significant differences in the activated pIGF1R and pSTAT3 were revealed in the 2 responders (PR) compared to the 2 non-responders (PD) | 26

  27. Slide 27: CAPTN-3: Conditionally-Activated Tri-Specific Antibody Platform

    Advancing First-in-Class Oncology Therapies CAPTN-3: Conditionally-Activated Tri- Specific Antibody Platform Lead candidate: IM1240 (CD3x5T4xNKG2A)

  28. Slide 28: A novel mechanism of action tri-specific antibody

    A novel mechanism of action tri-specific antibody • Multi-specific biologics is an expanding class of drugs getting a lot of interest in the industry • After initial success in hemato-oncology, new formats are being investigated in solid tumors • Technology displays several distinctive features: • D

  29. Slide 29: CAPTN-3 Platform Technology Advantages

    CAPTN-3 Platform Technology Advantages CAP / cleavage site: Human Serum Albumin (HSA) ▪ Safety: Activation only ▪ Improved stability in blood in the TME circulation ▪ Efficacy: better PK CD3 arm: NK cell arm: ▪ T cell engager ▪ NK cell engager ▪ T cell activation ▪ Checkpoint inhibitor Efficient a

  30. Slide 30: Unleashing both innate and adaptive immune systems

    Unleashing both innate and adaptive immune systems NK cells CD4+/CD8+ T cells CD8+ NKG2A+ T cells NK cell activation by CD4+/CD8+ T cells CD8+ NKG2A+ T cells inhibition of HLAE- activation through CD3 double activation through NKG2A/CD94 binding binding CD3 binding and NKG2A- HLA-E axis blocking | 3

  31. Slide 31: POC: NKG2A arm contributes to tumor cell killing

    POC: NKG2A arm contributes substantially to tumor cell killing and synergizes with the CD3 Arm 100 Increased cytotoxicity with 94 cResponse Score tribody format 80 60 CD3x5T4xNKG2A CD3x5T4 40 49 38 EC50 tribody: 0.003 nM EC50 bispecific: 0.066 nM 20 5 0 Control IM1242 5T4xNKG2A IM1340 5T4xCD3 IM124

  32. Slide 32: Cleavable capping leads to improved in vivo efficacy

    Cleavable capping leads to improved in vivo efficacy 600 Tumor Volume (mm3) Non- cleavable cap 400 control 200 Non cap Cleavable cap 0 0 3 6 10 13 17 20 24 27 31 Study Day • Sustained tumor regressions in TNBC xenograft model (MDA-MB-231) in CD34 engrafted humanized mice • The Pro-Tribody, Capped-CD

  33. Slide 33: 5T4: a Novel Target in Oncology

    5T4: a Novel Target in Oncology 5T4 is highly expressed on certain tumors 5T4 is a Tumor Associated Antigen and correlates with poor prognosis prevalent to several large indications Am J Cancer Res 2018;8(4):610-623 www.ajcr.us /ISSN:2156-6976/ajcr0074519 Opportunity of patient stratification strate

  34. Slide 34: Corporate highlights

    Corporate highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Multiple data read-outs expected in 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of March 31, 2024 • A preclinical tri-speci

  35. Slide 35: Thank You

    THANK YOU Contact Us: ir@purple-biotech.com | 35

  36. Slide 36: Appendix A | CM24

    ce foe i ~©Appendix A | CM24

  37. Slide 37: CEACAM1 Plays a Key Role in Cancer Biology

    CEACAM1 Plays a Key Role in Cancer Biology 01 | ADHESION 02 | IMMUNE CELLS/ 03 | IMMUNO-ONCOLOGY IMMUNE EXCLUSION Horst, 2011 Tsuzuki, 2020 Blumberg, 2015 “CEACAM1 creates a pro-angiogenic “Immune‐checkpoint molecules on “CEACAM1 regulates tumor microenvironment that regulatory T‐cells as a potentia

  38. Slide 38: CM24 Reduces Tumor Burden & Synergetic with α-PD-1

    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 days post

  39. Slide 39: Phase 1 Dose Escalation Interim Results

    Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combination with Nivolumab Study Design Safety • As of March 8th, 2022, a total of 13 patients were enrolled and 11 • No DLTs were observed across all dose levels; no Grade 4 patients were evaluable for DLT determination (8 P

  40. Slide 40: CM24 Phase 1 Combination Study (NCT04731467)

    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. Demographics of patients treated with CM24 (10, 15, 20mg/kg) • The primary objective of this part was t

  41. Slide 41: Confirmed Partial Response in a 3L PDAC Patient

    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 Partial Respo

  42. Slide 42: CM24 Phase 1 Dose Escalation Results

    CM24 Phase 1 Dose Escalation Results Encouraging data in 2L/3L Pancreatic Ductal Adenocarcinoma (PDAC) patients Study Results 14 patients were evaluable for efficacy: SD PR • Best overall response included 1 Partial SD Response (PR) (PDAC) and 4 Stable Disease (SD) (3 PDAC and 1 papillary thyroid ca

  43. Slide 43: Appendix B | NT219

    Appendix B | NT219

  44. Slide 44: Novel MOA: IRS Degradation By NT219

    Novel MOA: IRS Degradation By NT219 Blocking IGF1R-AKT Pathway1 1 Binding to IRS 2 Ser-phosphorylation 3 Degradation IGF1 IGF1R IGF1 IGF1 IGF1 IGF1R IGF1R IGF1R IRS NT pS PI3K IRS IRS pS AKT AKT AKT AKT CANCER CELL SURVIVAL CANCER CELL APOPTOSIS Covalent binding to IRS1/2 leads to the Serine phospho

  45. Slide 45: NT219 Re-sensitizes Tumors Refractory to α-PD1

    1200 NT219 Control (n=3) NT219 (n=3) Re-sensitizes 1000 Keytruda (n=3) Tumors Refractory Keytruda + NT219 (n=3) to α-PD1 Tumor volume (mm3) 800 PDX Model 600 Humanized PDX of GastroEsophageal Junction (GEJ) Cancer (refractory to 400 pembrolizumab) 200 Drug Pembrolizumab (Keytruda®) 0 0 5 10 15 20 Au

  46. Slide 46: Novel MOA: STAT3 Inhibition

    Novel MOA Signal Transducer and Activator of Transcription 3 (STAT3) 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 ecosystem and plays

  47. Slide 47: Simultaneous Blockade of STAT3 and AKT

    Simultaneous Blockade of STAT3 and AKT Pathways are Required to Overcome Resistance to EGFRi Overcoming drug resistance Proof of Concept: PDX model of Head and Neck Cancer Erlotinib Control (n=6) Erlotinib (n=8) EGFRi Erlotinib+NT219 (n=6) EGFR Erlotinib+Ruxolitinib (n=6) EGFR Erlotinib+Buparlisib (

  48. Slide 48: Selected Publications

    Selected Publications Michael Alexander Karin Levitzki Menashe Michael Bar-Eli Cox | 48

  49. Slide 49: NT219 Suppresses β-Catenin activity in CRC Cells

    NT219 Suppresses β-Catenin activity in CRC Cells and Inhibited CRC Brain Metastasis In Vitro In Vivo 5-FU Silencing IRS2 inhibits NT219 downregulates IRS2 and suppresses the -catenin activity CRC Cell Viability (72hr) -catenin activity DMEM β-catenin luciferase activity 1.5 *** iAKT DMEM (Relative

  50. Slide 50: NT219 | Pancreatic Cancer in Combination with Gemcitabine

    NT219 | Highly effective anti cancer activity exhibited by NT219 Pancreatic Cancer in combination with Gemcitabine in Combination with Gemcitabine PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar®) | 50

  51. Slide 51: RNA Sequencing | Analysis of Tumors Following Treatment

    Reduced expression of IRS1, Ki67, FOXM1 & TGFb is RNA Sequencing | exhibited by pancreatic cancer treated with NT219 alone and Analysis of Tumors in combination with gemcitabine Following Treatment PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar®) | 51

  52. Slide 52: NT219 suppresses CSC-mediated resistance to KRASG12C inhibitors

    NT219 suppresses cancer stem cell (CSC)-mediated resistance to KRASG12C inhibitors and synergizes with sotorasib to combat NSCLC NT219+sotorasib leads to disaggregation Enrichment of CSC population in established of established NSCLC spheroids Effect on CSC viability spheroid is suppressed by NT219

  53. Slide 53: NT219 overcomes resistance to KRASG12D inhibitors

    NT219 overcomes resistance to KRASG12D inhibitors and synergizes with MRTX1133 to combat pancreatic cancer A B AsPC1 IC50: IC50: 2.3M 0.3µM MRTX1133-R AsPC1 C D Control NT219 MRTX1133 NT219 +MRTX1133 Higher sensitivity of mKRAS(G12D)i resistant PDAC and synergy of NT219 with MRTX1133. a MRTX1133-re

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