Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (August 2024)
53 slides from Purple Biotech's investor presentation, Aug 19, 2024
Slide 1: Corporate Presentation August 2024
| 1 NASDAQ/TASE: PPBT August 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 June 30, 2024 • ADS Outstanding: 29.0 M • Cash Balance: $7.3 M • Additional $2 M raised in July 2024 Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2024 • Two
Slide 4: A pipeline dedicated to advancing oncology therapies
| 4 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 3Q24 □
Slide 5: Advancing First-in-Class Oncology Therapies: CM24
Advancing First - in - Class Oncology Therapies CM 24 : an α - CEACAM 1 * mAb Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC) *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 6: CM24: a new multi-functional CEACAM1 inhibitor
| 6 CM24: a new multi - functional CEACAM1 inhibitor • 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 cell s - mediated cytotoxicity against
Slide 7: CM24 MOA (#1): Immune check point inhibitor
| 7 CD CM24 MOA (#1) Immune check point inhibitor 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 cre
Slide 8: CM24 MOA (#2): Blocks NET oncogenic potential through CEACAM1 blockage
| 8 CM 24 MOA (# 2 ) B locks NET oncogenic potential thru CEACAM 1 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 o
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 CM 24 binds to CEACAM 1 on NETs Level of MPO in patient serum (% of Pre - treatment) p = 0.034
Slide 10: Large Market Opportunity in Pancreatic Cancer
| 10 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 mutationa
Slide 11: Phase 2 combination study of CM24 with nivolumab plus chemotherapy in PDAC
| 11 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 2024 Primary endpoint : OS Secondary endpoints: OS rate @ 6 & 12 m
Slide 12: Phase 2 interim data: Nal-IRI/5FU/LV sub-study
| 12 Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal/IRI/5FU/LV sub - study Control (n=15) Experimental (n=16) Characteristic 68 66 Age (median) 11 (73.3) 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 13: Phase 2 interim data: survival results
| 13 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 -
Slide 14: Phase 2 interim data: response rates
| 14 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 % change in tum
Slide 15: Phase 2 interim data: efficacy summary
| 15 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
Slide 16: Interim biomarker analysis: NET marker
| 16 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
Slide 17: Advancing First-in-Class Oncology Therapies: NT219
Advancing First - in - Class Oncology Therapies NT 219 : A Small Molecule Dual Inhibitor of IRS 1 / 2 and STAT 3 Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)
Slide 18: NT219, a new solution to improve treatment outcome
| 18 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 19: NT219 blocks critical signalling pathways at once
| 19 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 20: NT219 restores sensitivity to EGFRi in PDX models
| 20 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 21: NT219 re-sensitizes anti-PD-1 refractory model
| 21 NT 219 re - sensitizes PD 1 - 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
Slide 22: NT219 with anti-PD-1 reprograms the TME
| 22 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 (%
Slide 23: First Market Opportunity: Recurrent or Metastatic SCCHN
| 23 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 24: Phase 1 dose escalation in combination with cetuximab
| 24 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 25: Phase 1 efficacy overview
| 25 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 26: Activated IGF1R and STAT3 as potential predictive biomarkers
| 26 Activated IGF 1 R and STAT 3 as potential predictive biomarkers Biomarker analysis at the 50 mg/kg dose of NT 219 with cetuximab: • Significant differences in the activated pIGF 1 R and pSTAT 3 were revealed in the 2 responders (PR) compared to the 2 non - responders (PD)
Slide 27: Advancing First-in-Class Oncology Therapies: CAPTN-3
Advancing First - in - Class Oncology Therapies CAPTN - 3: Conditionally - Activated Tri - Specific Antibody Platform Lead candidate: IM1240 ( CD3x5T4xNKG2A)
Slide 28: A novel mechanism of action tri-specific antibody
| 28 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 aCD 3 masking moiety Tumor cell T cell NK cell Cancer microenvironment Protease cleavage Removal of T cell engager ’ s mask
Slide 29: CAPTN-3 Platform Technology Advantages
| 29 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 en
Slide 30: Unleashing both innate and adaptive immune systems
| 30 NK cells CD 4 + / CD 8 + T cells CD 8 + NKG 2 A + T cells NK cell activation by inhibition of HLAE - NKG2A/CD94 binding CD 4 + / CD 8 + T cells activation through CD 3 binding CD8 + NKG2A + T cells double activation through CD3 binding and NKG2A - HLA - E axis blocking Unleashing both innate an
Slide 31: Synergistic effect in patient-derived explant
| 31 5 38 49 94 0 20 40 60 80 100 Control IM1242 IM1340 IM1240 cResponse Score CD3x5T4 x NKG2A (cleavable cap IM1240 5 T 4 xNKG 2 A (non - cleavable) capped CD 3 ) 5T4xCD3 (cleavable cap; mutated NKG2A) • Synergistic effect of the CD 3 and NKG 2 A arms in suppressing 5 T 4 + NCSLC Patient - De
Slide 32: Cleavable capping leads to improved in vivo efficacy
| 32 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 33: 5T4: a Novel Target in Oncology
| 33 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 /ajcr 0074519 5 T 4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patient
Slide 34: Corporate highlights
| 34 Corporate highlights Purple Biotech (NASDAQ/TASE: PPBT) As of June 30 , 2024 • ADS Outstanding: 29.0 M • Cash Balance: $ 7.3 M • Additional $ 2 M raised in July 2024 Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2024 •
Slide 35: Contact Us / Thank You
| 35 Contact Us: ir@purple - biotech.com THANK YOU
Slide 36: Appendix A: CM24
Appendix A | CM 24
Slide 37: CEACAM1 Plays a Key Role in Cancer Biology
| 37 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 CEACAM1 as a putative therapeutic target to prevent metastatic progression of co
Slide 38: CM24 Reduces Tumor Burden and Is Synergistic with anti-PD-1
| 38 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 26
Slide 39: Phase 1 Dose Escalation Interim Results: Safety
| 39 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 40: CM24 Phase 1 Combination Study Demographics
| 40 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 41: Confirmed Partial Response in a 3L PDAC Patient
| 41 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 42: CM24 Phase 1 Dose Escalation Results
| 42 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 43: Appendix B: NT219
Appendix B | NT219 af
Slide 44: Novel MOA: IRS Degradation by NT219
| 44 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 45: NT219 Re-sensitizes Tumors Refractory to anti-PD-1
| 45 0 200 400 600 800 1000 1200 0 5 10 15 20 Tumor volume (mm 3 ) Days following treatment initiation Control (n=3) NT219 (n=3) Keytruda (n=3) Keytruda + NT219 (n=3) Autologous PBMCs ( 2.1 M/mouse) NT 219 Re - sensitizes Tumors Refractory to α - PD 1 PDX Model Humanized PDX of GastroEsophageal Junc
Slide 46: Novel MOA: STAT3 Inhibition
| 46 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 47: Simultaneous Blockade of STAT3 and AKT Pathways Overcomes EGFRi Resistance
| 47 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 48: Selected Publications
| 48 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 49: NT219 Suppresses Beta-Catenin Activity in CRC Cells
| 49 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 o
Slide 50: Pancreatic Cancer in Combination with Gemcitabine
| 50 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 51: RNA Sequencing Analysis of Tumors Following Treatment
| 51 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 52: NT219 suppresses CSC-mediated resistance to KRAS G12C inhibitors
| 52 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 53: NT219 overcomes resistance to KRAS G12D inhibitors
| 53 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 Meetin