Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (June 2024)
52 slides from Purple Biotech's investor presentation, Jun 4, 2024
Slide 1: Corporate Presentation June 2024
| 1 NASDAQ/TASE: PPBT June 2024 CORPORATE PRESENTATION
Slide 2: Forward-looking Statements and Safe Harbor
Forward - looking Statements and Safe Harbor | 2 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: Corporate highlights
Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of March 31, 2024 • ADS Outstanding: 26.6 M • Cash Balance: $10.8 M Strong position to reach short and mid term value creating clinical data catalysts | 3 • Multiple data read - outs expected in 2024 • Two First - in - Class clinical stage d
Slide 4: A pipeline dedicated to advancing oncology therapies
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 2H24 □ Phas
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
Slide 6: CM24: a new multi-functional immune checkpoint inhibitor
| 6 CM24: 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 • CM24 increases T cell and NK cells cytotoxi
Slide 7: CM24 MOA
| 7 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 RF,
Slide 8: CEACAM1 is over-expressed in pancreatic cancer
| 8 Representative examples of CEACAM1 immunohistochemical images of pancreatic adenocarcinoma and normal tissues Comparison between CEACAM1 staining intensity in pancreatic cancer (38 cases/76 cores) and normal (10 cases/20 cores) tissues CEACAM1 is over - expressed in pancreatic cancer
Slide 9: Large Market Opportunity in Pancreatic Cancer
| 9 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
Slide 10: Phase 2 combination study design
| 10 A study of CM24 in combination with nivolumab plus chemotherapy in patients with PDAC in the 2 nd line The study is conducted in 18 centers in the US, Spain & Israel Measurement of CEACAM1 and other bio - markers is ongoing 2023 Primary endpoint : OS Secondary endpoints: OS rate @ 6 & 12 months
Slide 11: Phase 2 interim data: patient characteristics
Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal/IRI/5FU/LV sub - study | 11 Control (n=15) Experimental (n=16) Characteristic 68 66 Age (median) 4 (26.7) 8 (50.0) Age ≥65 (n, %) 8 (53.3) 10 (62.5) Male (n, %) 7 (46.7) 6 (37.5) Female (n, %) 14 (93.3) 15 (93.8) Race/ white (n, %)
Slide 12: Phase 2 interim data: survival
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
Slide 13: Phase 2 interim data: response rates
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 Median CA 19 - 9 levels | 13 % change in tum
Slide 14: Phase 2 interim data: efficacy summary
| 14 Phase 2 interim data (cut off date - May 8, 2024) Efficacy summary Control (n=15) Experimental (n=16) Parameter 5.62 (3.22 - 7.89) 7.72 (4.00 - 8.11) OS (mo, median; 95% CI) 0.74 (0.31 - 1.77) OS HR (95% CI) 38.9 52.7 6 mo OS (%) 1.9 (0.9 - 3.6) 3.8 (1.8 - 5.0) PFS (mo, median; 95% CI) 0.72 (0.
Slide 15: 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 Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)
Slide 16: NT219, a new solution to improve treatment outcome
| 16 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 • Covalently binds to IRS1/2 and leads to their degradation • Affects both the tumor and the TME • Suppresses cancer stem cells Innovative M
Slide 17: NT219 blocks critical signalling pathways at once
| 17 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 multiple tumors • Regulates major survival pathways such as the PI 3 K/AKT, MEK/ERK
Slide 18: NT219 restores sensitivity to EGFRi in PDX models
| 18 NT219 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: NT219 re-sensitizes PD1-refractory model
| 19 NT219 re - sensitizes PD1 - refractory model 6 8 10 12 14 16 18 20 22 Days following tumor challenge 0 500 1000 1500 2000 Tumor volume (mm 3 ) Control (n=10) α - PD - 1 (n=10) NT219 (n=10) NT219+α - PD - 1 (n=10) PD1 - resistant melanoma cells (FACS analysis) PDL1 expression (MFI) NT219 (
Slide 20: NT219 with αPD1 reprograms the TME
| 20 NT219 combination with α PD1 achieves a profound reprograming of the TME NT219 and PD1 combination converted immuno - suppressive TME to immuno - reactive * Collaboration with Prof. Bareli and Prof. Curran, M.D. Anderson cancer center, presented at AACR 2023 Activated cytotoxic T cells (% CD8
Slide 21: First Market Opportunity: Recurrent or Metastatic SCCHN
First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Rationale for combining Cetuximab + NT219 • EGFR and PD(L) - 1 are the only clinically validated targets in SCCHN • < 15% of R/M SCCHN patients respond to Cetuximab • Cetuximab inhibits EGFR signaling a
Slide 22: Phase 1 dose escalation 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 e
Slide 23: Phase 1 efficacy overview
| 23 Efficacy overview of monotherapy arm : • 20 evaluable patients (all doses): 2 PR (confirmed - GEJ, unconfirmed - PDAC), 5 SD Efficacy overview of combination arm in SCCHN patients * : • 15 evaluable patients (all doses 6, 12, 24, 50, 100 mg/kg) • Median follow - up of 9.4 months (95% CI: 3.4 -
Slide 24: Activated IGF1R and STAT3 as potential predictive biomarkers
| 24 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)
Slide 25: 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)
Slide 26: A novel mechanism of action tri-specific antibody
| 26 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 aCD3 masking moiety Tumor cell T cell NK cell Cancer microenvironment Protease cleavage Removal of T cell engager’s masking
Slide 27: CAPTN Platform Technology Advantages
CAPTN - 3 Platform Technology Advantages CAP / cleavage site: ▪ Safety: Activation only in the TME ▪ Efficacy: better PK Human Serum Albumin (HSA) ▪ Improved stability in blood circulation CD3 arm: ▪ T cell engager ▪ T cell activation Efficient anti - tumor effect NK cell arm: ▪ NK cell engager
Slide 28: Unleashing both innate and adaptive immune systems
NK cells CD4 + /CD8 + T cells CD8 + NKG2A + T cells NK cell activation by inhibition of HLAE - NKG2A/CD94 binding CD4 + /CD8 + T cells activation through CD3 binding CD8 + NKG2A + T cells double activation through CD3 binding and NKG2A - HLA - E axis blocking Unleashing both innate and adaptive immu
Slide 29: Synergistic effect of CD3 and NKG2A arms
| 29 5 38 49 94 0 20 40 60 80 100 Control IM1242 IM1340 IM1240 cResponse Score CD3x5T4xNKG2A (cleavable cap IM1240 5T4xNKG2A (non - cleavable) capped CD3) 5T4xCD3 (cleavable cap; mutated NKG2A) • Synergistic effect of the CD3 and NKG2A arms in suppressing 5T4 + NCSLC Patient - Derived Explant
Slide 30: Cleavable capping leads to improved in vivo efficacy
Cleavable capping leads to improved in vivo efficacy 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 - CD3x5T4xNKG2A, performed better than the uncapped variant • PK analysis in
Slide 31: 5T4: a Novel Target in Oncology
5T4: a Novel Target in Oncology 5T4 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/ajcr0074519 5T4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patient stratification st
Slide 32: Corporate highlights
Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of March 31, 2024 • ADS Outstanding: 26.6 M • Cash Balance: $10.8 M Strong position to reach short and mid term value creating clinical data catalysts | 32 • Multiple data read - outs expected in 2024 • Two First - in - Class clinical stage
Slide 33: Contact Us / Thank You
| 33 Contact Us: ir@purple - biotech.com THANK YOU
Slide 34: Appendix A | CM24
Appendix A | CM24
Slide 35: CEACAM1 Plays a Key Role in Cancer Biology
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 colon ca
Slide 36: 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 p
Slide 37: Phase 1 Dose Escalation Interim Results: Safety
Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combination with Nivolumab Total Grade 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 2 2 Co
Slide 38: CM24 Phase 1 Combination Study Demographics
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 determi
Slide 39: 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
Slide 40: 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: • Best overall response included 1 Partial Response (PR) (PDAC) and 4 Stable Disease (SD) (3 PDAC and 1 papillary thyroid cancer (PTC
Slide 41: Exploratory biomarkers supporting CM24 mechanism of action
Phase 1 study results (cont.): Identification of potential exploratory biomarkers supporting CM24’s mechanism of action Higher pre - treatment levels of tumor infiltrating lymphocytes that express CEACAM1 are associated with longer survival • consistent with the CM24 MoA in suppressing the immune ev
Slide 42: Appendix B | NT219
Appendix B | NT219
Slide 43: Novel MOA: IRS Degradation By NT219
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 2 Ser - phosphorylation Degradation 3 Covalent binding to IRS1/2 leads to the dissociation of IRS1/2 from IGF1R Serine phosphorylation prevents re
Slide 44: NT219 Re-sensitizes Tumors Refractory to α-PD1
| 44 0 200 400 600 800 1000 1200 5 20 Tumor volume (mm 3 ) 10 15 Days following treatment initiation Control (n=3) NT219 (n=3) Keytruda (n=3) Keytruda + NT219 (n=3) 0 Autologous PBMCs (2.1 M/mouse) NT219 Re - sensitizes Tumors Refractory to α - PD1 PDX Model Humanized PDX of GastroEsophageal Junctio
Slide 45: Novel MOA: STAT3 Inhibition
| 45 Zou, S., Tong, Q., Liu, B. et al. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer 19, 145 (2020). https://doi.org/10.1186/s12943 - 020 - 01258 - 7 Novel MOA Signal Transducer and Activator of Transcription 3 (STAT3) Inhibition • Point of convergence for numerous oncogenic signaling pathways
Slide 46: Simultaneous Blockade of STAT3 and AKT Pathways
| 46 Simultaneous Blockade of STAT3 and AKT Pathways are Required to Overcome Resistance to EGFRi Overcoming drug resistance NT219 NT219 STAT3 IRS EGFR EGFRi MEK / ERK TUMOR REGRESSION Proof of Concept: PDX model of Head and Neck Cancer Control (n=6) Erlotinib (n=8) Erlotinib+NT219 (n=6) Erlotinib+R
Slide 47: Selected Publications
Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox | 47
Slide 48: NT219 Suppresses β-Catenin activity in CRC Cells
Colon cancer LS - 513 cells overexpressing IRS2 demonstrate enhanced - catenin activity. Targeted inhibition of IRS2 by NT219 or IRS2 - SH RNA, suppresses the increased - catenin activity and inhibit LS - 513 cell viability. Combination of 5 - FU and NT219 significantly inhibited the growth of C
Slide 49: Pancreatic Cancer in Combination with Gemcitabine
PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar ® ) NT219 | Pancreatic Cancer in Combination with Gemcitabine | 49 Highly effective anti cancer activity exhibited by NT219 in combination with Gemcitabine
Slide 50: RNA Sequencing Analysis of Tumors Following Treatment
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 | 50
Slide 51: NT219 and KRAS G12C inhibitor resistance in NSCLC
NT219 suppresses cancer stem cell (CSC) - mediated resistance to KRAS G12C inhibitors and synergizes with sotorasib to combat NSCLC Control NT219 Sotorasib Sotorasib +NT219 Effect on CSC viability 5 4 3 2 1 cell viability (luminescencex10 4 ) 3D growth (H358 NSCLC Spheroids) 2D growth 3D growth (H35
Slide 52: NT219 overcomes resistance to KRAS G12D inhibitors
| 52 NT219 overcomes resistance to KRAS G12D inhibitors and synergizes with MRTX1133 to combat pancreatic cancer B C D A NT219 Control MRTX1133 NT219 +MRTX1133 Higher sensitivity of mKRAS(G 12 D)i resistant PDAC and synergy of NT 219 with MRTX 1133 . a MRTX 1133 - resistant PDAC clone was developed