Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (May 2024)
44 slides from Purple Biotech's investor presentation, May 2, 2024
Slide 1: Corporate Presentation May 2024
| 1 NASDAQ/TASE: PPBT May 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 December 31, 2023 • ADS Outstanding: 25.2 M • Cash Balance: $15.3 M Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2024 • Two First - in - Class clinical stag
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 1H24 □
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 • C M24 increases T cell and NK cells cytotox
Slide 7: CM24 MOA Immune Check Point Inhibitor & Anti-Metastatic Activity
| 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: CM24 Phase 1 Dose Escalation Results
| 10 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 11: Phase 1 study results: exploratory biomarkers
| 11 Phase 1 study results (cont.): Identification of potential exploratory biomarkers supporting CM24’s mechanism of action Higher pre - treatment level s of tumor infiltrating lymphocytes that express CEACAM1 are associated with longer s urvival • consistent with the CM24 MoA in suppressing the im
Slide 12: Phase 2 Combination Study Design
| 12 n=60 PDAC patients progressing on or after 1L SoC Chemotherapy Ongoing - enrollment completed A study of CM24 in combination with nivolumab plus chemotherapy in PDAC patients in 2L treatment 18 centers are currently active in US, EU & Israel Measurement of CEACAM1 and other bio - markers is ong
Slide 13: Phase 2 interim data
| 13 Phase 2 interim data (cut off Feb 2024): • CM24/nivolumab + Nal - IRI/5FU/LV experimental arm vs. the Nal - IRI/5FU/LV control arm suggests: • Reduced risk of progression or death as demonstrated by PFS • Higher objective response rate (ORR) and disease control rate (DCR) • Decreasing CA19 - 9
Slide 14: 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 15: NT219, a new solution to improve treatment outcome
| 15 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 MOA • Outstanding efficacy in various PDX models in monotherapy and in combination • Uniquely positioned to tackle resistance t
Slide 16: NT219 blocks critical signalling pathways at once
| 16 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 17: NT219 Restores Sensitivity to EGFRi in PDX Models
| 17 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 18: NT219 induces PDL1 and re-sensitizes aPD1-refractory model
| 18 NT219 induces PDL1 and re - sensitizes aPD1 - 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 a PD 1 - resistant melanoma cells (FACS analysis) PDL1 expressi
Slide 19: NT219 combination with αPD1 reprograms the TME
| 19 NT 219 combination with α PD 1 achieves a profound reprograming of the TME NT219 and aPD1 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 (% CD
Slide 20: First Market Opportunity: Recurrent or Metastatic SCCHN
| 20 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 21: Phase 1 dose escalation in combination with cetuximab
| 21 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 22: Phase 1 Dose Escalation: anti-tumor activity
| 22 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: 3.4
Slide 23: Conditionally-Activated Tri-Specific Antibody Platform
Advancing First - in - Class Oncology Therapies Conditionally - Activated Tri - Specific Antibody Platform Lead candidate: IM1240 ( CD3x5T4xNKG2A)
Slide 24: A Novel Mechanism of Action: Tri-Specific Antibody Activated in TME
| 24 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 maski
Slide 25: Unleashing both Innate and Adaptive Immune Systems
| 25 NK - cells CD 4 + - T - cells CD 8 + - NKG 2 A + - T - cells NK cell activation by inhibition of HLAE - NKG 2 A/CD 94 binding CD 4 + - T - cells activation through CD 3 binding CD8 + - NKG2A + T - cells double activation through CD3 binding and NKG2A - HLA - E axis blocking Unleashing both Inna
Slide 26: Promising Proof of Concept Data
| 26 Promising Proof of Concept Data • Tribody induces p M EC 50 against A 549 cells • 20 - fold more potent than CD 3 x 5 T 4 variant • Cell killing validated on multiple 5 T 4 + cell lines (MDA - MB - 231 , HCT 116 , NCI - H 226 ) • Sustained tumor regressions in Breast Cancer xenograft humanized
Slide 27: 5T4: a Novel Target in Oncology
| 27 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/ajcr0074519 5T4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patient stratific
Slide 28: Corporate Highlights
| 28 Corporate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of December 31 , 2023 • ADS Outstanding: 25.2 M • Cash Balance: $ 15.3 M Strong position to reach short and mid term value creating clinical data catalysts • Multiple data read - outs expected in 2024 • Two First - in - Class clinical s
Slide 29: Contact Us / Thank You
| 29 Contact Us: ir@purple - biotech.com THANK YOU
Slide 30: Appendix A: CM24
Appendix A | CM 24
Slide 31: CEACAM Plays a Key Role in Cancer Biology
| 31 CEACAM 1 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 CEACAM 1 as a putative therapeutic target to prevent metastatic progression of c
Slide 32: CM24 Reduces Tumor Burden & Synergetic with α-PD-1
| 32 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
Slide 33: Phase 1 Interim Results: CM24 Safe in Combination with Nivolumab
| 33 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 34: CM24 Phase 1 Combination Study Demographics
| 34 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 35: Confirmed Partial Response in a 3L PDAC Patient
| 35 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 36: Appendix B: NT219
Appendix B | NT219
Slide 37: Novel MOA: IRS Degradation By NT219
| 37 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 38: NT219 Re-sensitizes Tumors Refractory to α-PD1
| 38 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 39: Novel MOA: STAT3 Inhibition
| 39 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 40: Simultaneous Blockade of STAT and AKT Pathways Overcomes Resistance to EGFRi
| 40 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 41: Selected Publications
| 41 Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox
Slide 42: NT219 Suppresses β-Catenin activity in CRC Cells
| 42 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 b - catenin activity. Targeted inhibition o
Slide 43: Pancreatic Cancer in Combination with Gemcitabine
| 43 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 44: RNA Sequencing Analysis of Tumors Following Treatment
| 44 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