Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (December 2024)
57 slides from Purple Biotech's investor presentation, Dec 6, 2024
Slide 1: Corporate Presentation December 2024
| 1 NASDAQ/TASE: PPBT December 2024 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 September 30, 2024 • ADS Outstanding: 1.7 M • Cash Balance: $6.3 M • Additional $4.0 M raised Dec 24 Well positioned to advance next clinical milestones • Two First - in - Class clinical stage drugs • A preclinical tri - specific immu
Slide 4: A pipeline dedicated to advancing oncology therapies
| 4 A pipeline dedicated to advancing oncology therapies Clinical Benefit Demonstrated for CM24 & NT219 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 □ Initiatio
Slide 5: Advancing First-in-Class Oncology Therapies 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 through CEACAM1 blockage
| 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 ) • CEA
Slide 9: CM24 MOA (#2 cont.) Blocks NET oncogenic potential
| 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 CM 24 opportunity in PDAC • Pancreatic Cancer accounts for ~ 60 K 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 lin
Slide 11: Phase 2 study of CM24 with nivolumab plus chemotherapy in 2nd line PDAC
| 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: Phase 2 final analysis: ITT population demographics
| 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 final analysis: safety population
| 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: Phase 2 final analysis: PFS and OS
| 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: Phase 2 final analysis: ORR and DCR
| 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: Phase 2 final analysis - 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: Phase 2 final biomarker analysis: 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: Phase 2 final biomarker analysis: 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: Phase 2 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: 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 21: NT219, a new solution to improve treatment outcome for cancer patients
| 21 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 22: NT219 blocks critical signalling pathways at once
| 22 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 23: NT219 restores sensitivity to EGFRi in PDX models
| 23 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 24: NT219 re-sensitizes PD1-refractory model
| 24 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 25: NT219 combination with α-PD1 reprograms the TME
| 25 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 26: First Market Opportunity: Recurrent or Metastatic SCCHN
| 26 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 27: Phase 1 dose escalation in combination with cetuximab
| 27 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 Do
Slide 28: Phase 1 Dose Escalation: anti-tumor activity at target exposure
| 28 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 * : • 15 evaluable patients (all doses 6 , 12 , 24 , 50 , 100 mg/kg ) • Median follow - up of 9.4 months ( 95 % CI
Slide 29: Activated IGF1R and STAT3 as potential predictive biomarkers
| 29 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 30: 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 31: A Novel Mechanism of Action Tri-Specific Antibody
| 31 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 fe
Slide 32: CAPTN Platform Technology Advantages
32 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 CD 3 arm: ▪ T cell engager ▪ T cell activation Efficient anti - tumor effect NK cell arm: ▪ NK cell engager
Slide 33: Unleashing both innate and adaptive immune systems
| 33 Unleashing both innate and adaptive immune systems
Slide 34: IM1240 synergistic effect in NSCLC patient-derived explant
| 34 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 35: Cleavable capping leads to improved in vivo efficacy
| 35 Cleavable capping leads to improved in vivo efficacy • Sustained tumor regressions in TNBC xenograft model (MDA - MB - 231 ) in CD 34 engrafted humanized mice • T he Pro - Tribody , Capped - CD 3 x 5 T 4 xNKG 2 A, performed better than the uncapped variant • PK analysis in normal mice showed 3
Slide 36: Improved safety profile: cytokine release suppressed by the cap
| 36 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 5T4 - expressing cancer cells the non - capped variant showed a decreased IFN rele
Slide 37: 5T4: a Novel Target in Oncology
| 37 5 T 4 : 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 /ajcr 0074519 5 T 4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patien
Slide 38: Corporate highlights
| 38 Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of September 30 , 2024 • ADS Outstanding: 1.7 M • Cash Balance: $ 6.3 M • Additional $ 4.0 M raised Dec 24 Well positioned to advance next clinical milestones • Two First - in - Class clinical stage drugs • A preclinical tri - specific
Slide 39: Contact Us / Thank You
| 39 Contact Us: ir@purple - biotech.com THANK YOU
Slide 40: Appendix A: CM24
Appendix A | CM 24
Slide 41: CEACAM Plays a Key Role in Cancer Biology
| 41 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 42: CM24 Reduces Tumor Burden and Synergizes with α-PD-1
| 42 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 43: Phase 1 Dose Escalation Interim Results: CM24 Safe in Combination with Nivolumab
| 43 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 44: CM24 Phase 1 Combination Study Demographics
| 44 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 45: Confirmed Partial Response in a 3L PDAC Patient
| 45 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 46: CM24 Phase 1 Dose Escalation Results
| 46 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 47: Appendix B: NT219
Appendix B | NT219
Slide 48: Novel MOA: IRS Degradation by NT219
| 48 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 49: NT219 Re-sensitizes Tumors Refractory to α-PD1
| 49 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 50: Novel MOA: STAT3 Inhibition
| 50 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 51: Simultaneous Blockade of STAT3 and AKT Pathways to Overcome EGFRi Resistance
| 51 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 52: Selected Publications
| 52 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 53: IRS2 and β-catenin pathway data in colon cancer
| 53 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 54: NT219 in Pancreatic Cancer in Combination with Gemcitabine
| 54 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 55: RNA Sequencing Analysis of Tumors Following Treatment
| 55 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 56: NT219 suppresses CSC-mediated resistance to KRAS G12C inhibitors
| 56 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 57: NT219 overcomes resistance to KRAS G12D inhibitors
| 57 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
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