Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (March 2025)
59 slides from Purple Biotech's investor presentation, March 2025
Slide 1: Corporate Presentation
CORPORATE PRESENTATION NASDAQ/TASE: PPBT March 2025 |1
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
Slide 3: Corporate highlights
Corporate highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Two First-in-Class clinical stage drugs Purple Biotech (NASDAQ/TASE: PPBT) • A preclinical tri-specific immuno-engagers platform As of December 31, 2024 • Lean & gl
Slide 4: A pipeline dedicated to advancing oncology therapies
A pipeline dedicated to advancing oncology therapies Project Target Indications Development Stage Value Drivers collaborator Pre-Clinical Phase I Phase II Phase III CEACAM1 Pancreatic Cancer ❖ Initiation of CM24 mAb (+nivolumab+SoC) Phase 2b 2H25 Head and Neck ❖ Initiation of STAT3xIRS1/2 NT19 (+Cet
Slide 5: Advancing First-in-Class Oncology Therapies: CM24
Advancing First-in-Class Oncology Therapies CM24: an α-CEACAM1* mAb Significant opportunity in multiple large indications with unmet medical need Clinical POC achieved *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 6: CM24: POC of a potential CEACAM1-targeting therapy
CM24: POC of a potential CEACAM1-targeting therapy 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 tumor
Slide 7: CM24 MOA (#1) Immune modulation
CM24 MOA (#1) Immune modulation 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 Representative ex
Slide 8: CM24 MOA (#2) Blocks NET oncogenic potential
CM24 MOA (#2) Blocks NET oncogenic potential through 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 • CEA
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
Slide 10: Significant opportunity in multiple large indications with unmet medical need
Significant opportunity in multiple large indications with unmet medical need • CEACAM1 is upregulated in different cancer indications: >90% in Colon and Bladder and >70% in Lung, Gastric, breast, and other 1 • Elevated levels of neutrophil extracellular traps (NETs) have been observed in various ca
Slide 11: Phase 2 Combination Study Design
Phase 2 Combination Study Design (NCT04731467) A study of CM24 in combination A substantial rate of early Measurement of biomarkers: Primary endpoint : with nivolumab* plus discontinuation in the control CEACAM1, OS chemotherapy in patients with arm of the gemcitabine/ NET marker Secondary endpoints
Slide 12: Phase 2 final analysis: demographics
Phase 2 final analysis Intent to Treat (ITT) Population demographics and patient characteristics Nal-IRI/5FU/LV Characteristic Experimental (n=16) Control (n=15) Age (median) 66.0 68.0 Male (n, %) 10 (62.5) 8 (53.3) Female (n, %) 6 (37.5) 7 (46.7) Race/ white (n, %) 15 (93.8) 14 (93.3) BMI (median)
Slide 13: Phase 2 final analysis: safety
Phase 2 final analysis Safety Population the most frequent related Grade ≥3 TEAEs Nal-IRI/5FU/LV Grade ≥3 TEAE Experimental (n=16) Control (n=15) N (%) N (%) Neutropenia 2 ( 12.5) 0 ( 0.0) Diarrhea 4 ( 25.0) 1 ( 6.7) Fatigue 2 ( 12.5) 0 ( 0.0) Anaemia 0 ( 0.0) 0 ( 0.0) Nausea 1 ( 6.3) 0 ( 0.0) Vomit
Slide 14: Phase 2 final analysis: survival
Phase 2 final analysis CM24+nivolumab+Nal-IRI/5FU/LV sub-study ➢ 19% reduction in risk of death (HR=0.81) and 25% reduction in the risk of progression or death (HR=0.75) ➢ Prolongation of 2.3 months in median overall survival and 1.9 months in median progression-free survival Overall Survival Progre
Slide 15: Phase 2 final analysis: response rates
Phase 2 final analysis CM24+nivolumab+Nal-IRI/5FU/LV sub-study ➢ Higher objective response rate (ORR) (25% vs 6.7%) ➢ Higher disease control rate (DCR) (62.5% vs 46.7%) ➢ Consistent and continuous decrease in CA19-9 was observed % change in tumor size Median CA 19-9 levels | 15
Slide 16: Phase 2 final analysis - Efficacy summary
Phase 2 final analysis-Efficacy summary CM24+nivolumab+Nal-IRI/5FU/LV sub-study Parameter Nal-IRI/5FU/LV Experimental Control OS (median, m; 95% CI) 7.92 (4.14, 8.02) 5.55 (3.45, 7.56) OS HR (95% CI) 0.81 (0.38,1.71) 6m OS rate (%) 53.6 46.7 PFS (median, m; 95% CI) 3.91 (1.84, 5.13) 1.97 (0.95, 3.78
Slide 17: Phase 2 biomarker analysis: serum CEACAM1
Phase 2 final biomarker analysis data Results for pre-treatment serum CEACAM1 level Statistically significant results in patients with pre-treatment serum CEACAM1 level between 6K to 15K: ➢ 79% reduction in the risk of death (HR = 0.21) and > 90% reduction in the risk of progression or death (HR < 0
Slide 18: Phase 2 biomarker analysis: CEACAM1 or MPO
Phase 2 final biomarker analysis Results for pre-treatment serum CEACAM1 or NET marker MPO levels Statistically significant results in patients with defined pre-treatment serum CEACAM1 or MPO levels in 80% of patients in the study: ➢ 61% reduction in risk of death (HR = 0.39) and 72% reduction in th
Slide 19: Phase 2 biomarker analysis: CEACAM1 and PDL1 in tumors
Phase 2 final biomarker analysis data Results for CEACAM1 and PDL1 levels in tumors Statistically significant results for patients with High CEACAM1 (H-score>100) and Low PDL1 (CPS ≤ 1 ) expression in tumors: ➢ 90% reduction in risk of death (HR = 0.1) and 81% reduction in the risk of progression or
Slide 20: CM24 path forward
CM24 path forward Novel MoA-directed opportunity Completed Future development Phase 2b MOA/Biomarker- Randomized Phase 2 P2b driven study POC study in (pancreatic, 2L PDAC patients gastric/ esophageal) • Multiple opportunities to leverage the novel MoA in other clinical settings and indications (e.g
Slide 21: Advancing First-in-Class Oncology Therapies: NT219
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 22: NT219, a new solution to improve treatment outcome
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
Slide 23: NT219 blocks 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
Slide 24: 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
Slide 25: 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
Slide 26: 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
Slide 27: First Market Opportunity: SCCHN
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
Slide 28: 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
Slide 29: 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, 100 90 unconfirmed-PDAC), 5 SD 80 Best % change from baseline 70 60 Efficacy overview
Slide 30: 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) | 30
Slide 31: Planned phase 2 study evaluating NT219 in r/m SCCHN
Planned phase 2 study evaluating NT219 in r/m SCCHN Simon 2 stage design enrolling 10 patients at 1st stage at RP2D Cohort A Cohort B NT219 in combination with NT219 in combination with pembrolizumab: cetuximab: ➢ 1L (ICI naïve) ➢ 2L (failed ICI) ➢ 2L (post ICI) In collaboration with Phase 2 is plan
Slide 32: 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 33: CAPTN-3 Platform
CAPTN-3 Platform 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 • Platform displays several distinctiv
Slide 34: 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
Slide 35: Unleashing both innate and adaptive immune systems
Unleashing both innate and adaptive immune systems | 35
Slide 36: 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
Slide 37: In vivo efficacy - significant and sustained tumor regression
In vivo efficacy - significant and sustained tumor regression In vivo anti-tumor efficacy of IM1240 & IM1222 Treatment Days following treatment initiation • Effective cleavage leading to significant tumor regression by both capped and non capped tribodies (p<0.0001). • No tumor recurrence observed •
Slide 38: Improved safety profile: Cytokine release suppressed by the cap
Improved safety profile: Cytokine release is 5T4-dependent and suppressed by the cap • The capped variant vs the non capped, showed a decreased IFN release > 150-fold (Safety factor #1). • In the absence of 5T4-expressing cancer cells the non-capped variant showed a decreased IFN release ~50-fold
Slide 39: 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
Slide 40: Corporate highlights
Corporate highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Two First-in-Class clinical stage drugs Purple Biotech (NASDAQ/TASE: PPBT) • A preclinical tri-specific immuno-engagers platform As of December 31, 2024 • Lean & gl
Slide 41: Thank You
THANK YOU Contact Us: ir@purple-biotech.com | 41
Slide 42: Appendix A | CM24
ce foe i ~©Appendix A | CM24
Slide 43: 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
Slide 44: 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
Slide 45: 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
Slide 46: CM24 Phase 1 Combination Study
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
Slide 47: 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
Slide 48: 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
Slide 49: Appendix B | NT219
Appendix B | NT219
Slide 50: 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
Slide 51: 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
Slide 52: 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
Slide 53: 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 (
Slide 54: Selected Publications
Selected Publications Michael Alexander Karin Levitzki Menashe Michael Bar-Eli Cox | 54
Slide 55: NT219 inhibits the IRS to β-Catenin pathway
NT219 inhibits the IRS to β-Catenin pathway and synergizes with 5FU to suppress CRC tumor growth in mouse brain In Vitro In Vivo A. Silencing IRS2 inhibits C. DAPI IRS2 β-catenin Merge D. B. NT219 downregulates IRS2 and suppresses the -catenin activity LS513sh-IRS2 LS513sh-NS -catenin activity 1 1
Slide 56: 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®) | 56
Slide 57: 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®) | 57
Slide 58: NT219 overcomes 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
Slide 59: 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: 2.3M 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