Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (March 2025)
58 slides from Purple Biotech's investor presentation, Mar 18, 2025
Slide 1: Corporate Presentation March 2025
| 1 NASDAQ/TASE: PPBT March 2025 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: Corporate highlights
| 3 Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of December 31, 2024 • ADS Outstanding: 2.6 M • Cash Balance: $8.2 M Well positioned to advance next clinical milestones • Two First - in - Class clinical stage drugs • A preclinical tri - specific immuno - engagers platform • Lean & glo
Slide 4: A pipeline dedicated to advancing oncology therapies
| 4 collaborator Value Drivers Development Stage Indications Target Project Phase III Phase II Phase I Pre - Clinical □ Initiation of Phase 2b 2H25 Pancreatic Cancer (+ nivolumab+SoC ) CEACAM1 mAb CM24 □ Initiation of Phase 2 1H25 Head and Neck (+Cetuximab/ pembrolizumab) STAT3xIRS1/2 Dual Inhibitor
Slide 5: CM24: an α-CEACAM1 mAb
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
| 6 CM24: POC of a potential CEACAM1 - targeting therapy • CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells • CEACAM1 is a part of the Neutrophil Extracellular Traps (NETs) structure Attractive new target • C M24 increases T cell and NK ce lls - mediated cytotoxicity aga
Slide 7: CM24 MOA (#1) Immune modulation
| 7 CD CM24 MOA (#1) Immune modulation 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. ; Gerstel, D. et al. CEACAM1 creates a pro
Slide 8: CM24 MOA (#2) Blocks NET oncogenic potential
| 8 CM24 MOA (#2) B locks NET oncogenic potential thr o u gh CEACAM1 blockage • Neutrophil extracellular traps ( NETs) are web - like structures involved in: » Tumor immune evasion (1, 3) » Tumor progression (1, 2, 6) » Metastasis (2, 3, 5, 6) » Cancer - associated thrombosis (4) • CEACAM1 is a part
Slide 9: CM24 MOA (#2 cont.)
| 9 CM24 MOA (#2 cont.) B locks NET oncogenic potential thru CEACAM1 blockage MPO ( green ) DAPI ( blue ), CM24 ( red ) CM24 ( red ) CM24 Inhibits NET - Induced migration of CEACAM1 expressing cancer cells CM24 binds to CEACAM1 on NETs Level of MPO in patient serum (% of Pre - treatment) p = 0.034 p
Slide 10: CM24 opportunity in PDAC
| 10 CM24 opportunity in PDAC • Pancreatic Cancer accounts for ~60K new cases/year in the US alone; with a 5 - year relative survival rate of 12. The 5 - year overall survival rate with chemotherapy in 2 nd line patients is 3% 4 • Two main interchangeable regimens are used worldwide in 2 nd line wit
Slide 11: Phase 2 combination study design
| 11 A study of CM24 in combination with nivolumab* plus chemotherapy in patients with PDAC in the 2 nd line 18 centers in the US, Spain & Israel Each cohort was a separate study Patients were randomized after assignment to chemo regimen Measurement of biomarkers: CEACAM1, NET marker (Myeloperoxidas
Slide 12: Population demographics and patient characteristics
| 12 Nal - IRI/5FU/LV Control (n=15) Experimental (n=16) Characteristic 68.0 66.0 Age (median) 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, %) 23.1 23.4 BMI (median) 3 (20.0) 5 (31.3) ECOG (n, %) 0 12 (80.0) 11 (68.8) 1 ϭϳ͘ϲ ͘ ϭϳ 8 Time from init
Slide 13: Phase 2 safety analysis
| 13 Nal - IRI/5FU/LV Grade ≥3 TEAE Control (n=15) N (%) Experimental (n=16) N (%) 0 ( 0.0) 2 ( 12.5) Neutropenia 1 ( 6.7) 4 ( 25.0) Diarrhea 0 ( 0.0) 2 ( 12.5) Fatigue 0 ( 0.0) 0 ( 0.0) Anaemia 0 ( 0.0) 1 ( 6.3) Nausea 0 ( 0.0) 1 ( 6.3) Vomiting 0 ( 0.0) 0 ( 0.0) Thrombocytopenia 0 ( 0.0) 0 ( 0.0)
Slide 14: Progression free survival and overall survival
| 14 Phase 2 final analysis CM24+nivolumab+Nal - IRI/5FU/LV sub - study Progression Free Survival Overall Survival » 19 % reduction in risk of death (HR=0. 81 ) and 2 5 % reduction in the risk of progression or death (HR=0.7 5 ) » Prolongation of 2. 3 months in median overall survival and 1.9 months
Slide 15: Objective response and disease control rates
| 15 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 Median CA 19 - 9 levels % change in tumor size
Slide 16: Efficacy summary
| 16 Phase 2 final analysis - Efficacy summary CM24+nivolumab+Nal - IRI/5FU/LV sub - study Concordant and consistent improvement in the primary and all secondary efficacy endpoints Nal - IRI/5FU/LV Parameter Control Experimental 5.55 (3.45, 7.56) 7.92 (4.14, 8.02) OS (median, m; 95% CI) 0.81 (0.38,1
Slide 17: Biomarker analysis: pre-treatment serum CEACAM1
| 17 Phase 2 final biomarker analysis data Results for p re - 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
Slide 18: Biomarker analysis: serum CEACAM1 or MPO levels
| 18 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 %
Slide 19: Biomarker analysis: CEACAM1 and PDL1 in tumors
| 19 Overall Survival (%) HR = 0.1 (0.01 - 0.89) Median = 7.9m vs 3.9m = 4m P = 0.013 Statistically significant results for patients with High CEACAM1 (H - score>1 00 ) and Low PDL1 ( CPS ≤ 1 ) expression in tumors : » 90 % reduction in risk of death ( HR = 0. 1 ) and 81 % reduction in the risk of p
Slide 20: CM24 path forward
| 20 CM24 path forward Novel MoA - directed opportunity • Multiple opportunities to leverage the novel MoA in other clinical settings and indications (e.g., pancreatic, GI, BTC, Lung, Colon, melanoma) • Potential targeting patients per pre - treatment serum CEACAM1 and MPO levels • Biomarkers data o
Slide 21: 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 22: NT219, a new solution to improve treatment outcome
| 22 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 23: NT219 blocks critical signalling pathways at once
| 23 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 PI3K/AKT, MEK/ERK a
Slide 24: NT219 restores sensitivity to EGFRi in PDX models
| 24 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 25: NT219 re-sensitizes PD1-refractory model
| 25 NT219 re - sensitizes PD1 - refractory model 6 8 10 12 14 16 18 20 22 0 500 1000 1500 2000 Control α-PD-1 NT219 NT219+α-PD-1 Days post tumor challenge T u m o r v o l u m e ( m m 3 ) Days following tumor challenge PD 1 - resistant melanoma cells (FACS analysis) PDL1 expression (MFI) NT219 ( M)
Slide 26: Combination with αPD1 reprograms the TME
| 26 NT 219 combination with α PD 1 achieves a profound reprograming of the TME NT 219 and PD 1 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 (% C
Slide 27: First Market Opportunity: Recurrent or Metastatic SCCHN
| 27 First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Global Data Epidemiology and Market Size for 8MM, accessed March 2025. Rationale for combining cetuximab or pembrolizumab + NT 219 • EGFR and PD(L) - 1 are the only clinically validated targets in
Slide 28: Phase 1 dose escalation in combination with cetuximab
| 28 Phase 1 dose escalation in combination with cetuximab: Well tolerated, target exposure reached, patient ’ s responses observed • No DLTs reported, NT 219 was well tolerated as monotherapy and in combination with cetuximab • Dose - proportional increase in AUC and Cmax values • Human Equivalent
Slide 29: Phase 1 dose escalation: anti-tumor activity
| 29 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 * : • 16 evaluable patients (all doses 6, 12, 24, 50, 100 mg/kg ) • Median follow - up of 9.4 months (95% CI: 3.4
Slide 30: Activated IGF1R and STAT3 as potential predictive biomarkers
| 30 Activated IGF 1 R and STAT 3 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 31: 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 32: CAPTN Platform
| 32 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 sever
Slide 33: CAPTN-platform technology advantages
33 CAPTN - 3 platform technology a dvantages CAP / cleavage site: ▪ Safety: Activation only in the TME ▪ Efficacy: better PK Human Serum Albumin (HSA) ▪ Improved stability in blood circulation CD 3 arm: ▪ T cell engager ▪ T cell activation Efficient anti - tumor effect NK cell arm: ▪ NK cell engager
Slide 34: Unleashing both innate and adaptive immune systems
| 34 Unleashing both innate and adaptive immune systems
Slide 35: Synergistic effect of CD3 and NKG2A arms
| 35 5 38 49 94 0 20 40 60 80 100 Control IM1242 IM1340 IM1240 cResponse Score CD 3 x 5 T 4 x NKG 2 A (cleavable cap) IM 1240 5 T 4 xNKG 2 A (non - cleavable) capped CD 3 ) 5 T 4 xCD 3 (cleavable cap; mutated NKG 2 A) • Synergistic effect of the CD 3 and NKG 2 A arms in suppressing 5 T 4 + NCSLC Pat
Slide 36: In vivo efficacy - tumor regression
| 36 In vivo efficacy - significant and sustained tumor regression • Effective cleavage leads to significant tumor regression by both capped and non - capped tribodies ( p< 0.0001 ). • No tumor recurrence observed • Frequency of administration - QOD TNBC MDA - MB - 231 cells were s.c. inoculated 1:1
Slide 37: Improved safety profile: cytokine release
| 37 Improved safety profile: Cytokine release is 5 T 4 - 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 5 T 4 - expressing cancer cells the non - capped variant showed a decreased IFN
Slide 38: 5T4: a Novel Target in Oncology
| 38 5T4: 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/ajcr0074519 5 T 4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patient stratifi
Slide 39: Corporate highlights
| 39 Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of December 31 , 2024 • ADS Outstanding: 2.6 M • Cash Balance: $ 8.2 M Well positioned to advance next clinical milestones • Two First - in - Class clinical stage drugs • A preclinical tri - specific immuno - engagers platform • Lean &
Slide 40: Thank you
| 40 Contact Us: ir@purple - biotech.com THANK YOU
Slide 41: Appendix A | CM24
Appendix A | CM24 Ae 2 Se
Slide 42: CEACAM1 Plays a Key Role in Cancer Biology
| 42 CEACAM1 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 c
Slide 43: CM24 Reduces Tumor Burden & Synergetic with α-PD-1
| 43 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 44: Phase 1 Dose Escalation Interim Results
| 44 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 45: CM24 Phase 1 Combination Study Demographics
| 45 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 46: Confirmed Partial Response in a 3L PDAC Patient
| 46 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 47: CM24 Phase 1 Dose Escalation Results
| 47 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 cance
Slide 48: Appendix B | NT219
Appendix B | NT219
Slide 49: Novel MOA: IRS Degradation By NT219
| 49 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 50: NT219 Re-sensitizes Tumors Refractory to α-PD1
| 50 NT 219 Re - sensitizes Tumors Refractory to α - PD 1 PDX Model Humanized PDX of GastroEsophageal Junction (GEJ) Cancer (refractory to pembrolizumab) Drug Pembrolizumab (Keytruda®) 0 200 400 600 800 1000 1200 0 5 10 15 20 Tumor volume (mm 3 ) Days following treatment initiation Control (n=3) NT2
Slide 51: Novel MOA: STAT3 Inhibition
| 51 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 52: Simultaneous Blockade of STAT and AKT Pathways
| 52 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 53: Selected Publications
| 53 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 54: NT219 publications and data in colon cancer
| 54 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 - catenin activity. Targeted inhibition of
Slide 55: Pancreatic Cancer in Combination with Gemcitabine
| 55 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 56: RNA Sequencing Analysis of Tumors Following Treatment
| 56 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
Slide 57: NT219 suppresses CSC-mediated resistance to KRAS G12C inhibitors
| 57 NT 219 suppresses cancer stem cell (CSC) - mediated resistance to KRAS G 12 C inhibitors and synergizes with sotorasib to combat NSCLC Control NT 219 Sotorasib Sotorasib +NT 219 Effect on CSC viability 5 4 3 2 1 cell viability (luminescencex 10 4 ) 3 D growth (H 358 NSCLC Spheroids) 2 D growth
Slide 58: NT219 overcomes resistance to KRAS G12D inhibitors
| 58 NT 219 overcomes resistance to KRAS G 12 D inhibitors and synergizes with MRTX 1133 to combat pancreatic cancer B C D A NT 219 Control MRTX 1133 NT 219 +MRTX 1133 IC 50 : 0.3 µM IC 50 : 2.3 M AsPC 1 AsPC 1 MRTX 1133 - R Collaboration n with Dr. Azmi, Karmanos . Presented at AACR Annual Meeting