Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (September 2023)
44 slides from Purple Biotech's investor presentation, Sep 13, 2023
Slide 1: Corporate Presentation September 2023
| 1 NASDAQ/TASE: PPBT September 2023 CORPORATE PRESENTATION
Slide 2: Forward-looking Statements and Safe Harbor
Forward - looking Statements and Safe Harbor | 2 Certain statements in this press release 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
Slide 3: Corporate Highlights
Corporate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of June 30, 2023 • ADS Outstanding: 21.4 M • Cash Balance : $18 M Strong position to reach short and mid term value creating clinical data catalysts | 3 • Multiple data read - outs expected in 2023 & 2024 • Two First - in - Class clinical st
Slide 4: Leadership Team
Leadership Team Hadas Reuveni, PhD VP Research & Development Formerly at Keryx (NASDAQ:KERX) Michael Schickler, PhD Head of Clinical and Regulatory Affairs Formerly at Hoffmann - La Roche, CEO at CureTech Gil Efron Chief Executive Officer Former Deputy CEO & CFO at Kamada (NASDAQ:KMDA) Fabien Sebill
Slide 5: A Pipeline Dedicated to Advancing Oncology Therapies
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 2 H 23 & 1
Slide 6: Advancing First-in-Class Oncology Therapies: CM24
Advancing First - in - Class Oncology Therapies CM24: an α - CEACAM1* mAb Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC) *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 7: CM24: a New Multi-Functional Immune Checkpoint Inhibitor
| 7 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 • CM24 increases T cell and NK cells cytotoxi
Slide 8: CM24 MOA
| 8 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 9: CEACAM1 is Over-Expressed in Pancreatic Cancer
| 9 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 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 11.5% 1 • Immuno - oncology approaches have been limited to patients with high microsatellite instability (MSI - H) or high tumor mutatio
Slide 11: CM24 Phase 1 Dose Escalation Results
| 11 CM24 Phase 1 Dose Escalation Results Encouraging 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 cancer
Slide 12: CM24 with nivolumab plus chemotherapy in PDAC: Phase 2 study
| 12 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 ongoing 2023 2024 Primary endpoint : OS Secondary endpoints: PFS, OS rate @ 6 & 12 months, PFS ra
Slide 13: 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 14: NT219 - A Novel Approach to Overcome Resistance to EGFRi
| 14 NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond • NT219 is a First - in - Class small molecule • Dual inhibitor of IRS1/2 and STAT3, two major drivers of resistance to cancer therapies Novel MOA • Significant efficacy in multiple in - vivo models • Modulation of the tumor mi
Slide 15: NT219 blocks critical signalling pathways at once
| 15 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 PI 3 K/AKT, MEK/ERK
Slide 16: Strong Efficacy in Monotherapy
Animal model Head & Neck Cancer (SCC - 9) NSG Ρ , immuno - competent Drugs α - PD1 Cetuximab NT219 Strong Efficacy in Monotherapy • NSG mice were injected SC with SCC - 9 cells. • PBMCs (18*10 6 cells per mouse) administered 4 weeks prior to first treatment. • NT219 (IV), α - PD1 (IP), and cetuximab
Slide 17: NT219 Restores Sensitivity to EGFRi in PDX Models
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 head
Slide 18: First Market Opportunity: Recurrent or Metastatic SCCHN
| 18 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 estimates of patient numbers based on external research,8 major global te
Slide 19: NT219 Phase 1 Monotherapy Interim Results
NT219 Phase 1 Dose Escalation Monotherapy Interim Results Study Design • As of data cutoff date of May 12 th , 2022, a total of 14 patients were enrolled and 12 patients were evaluable for dose limiting toxicity (DLT) determination (4 colorectal cancer, 3 pancreatic cancer, 2 breast cancer, 1 GEJ, 1
Slide 20: NT219 Interim Results: Encouraging Initial Efficacy Signals
NT219 Phase 1 Dose Escalation Monotherapy Interim Results: Encouraging Initial Efficacy Signals • For the 12 evaluable patients, best overall response included one confirmed Partial Response (gastroesophageal junction ( GEJ) patient, > 5.5 months duration of response following end of treatment), and
Slide 21: NT219 Monotherapy and Combination Phase 1/2 Study Design
| 21 NT219 Monotherapy and Combination Phase 1/2 Study Design (NCT04474470) Study Title A Phase 1/2 study with open - label, dose escalation phase followed by single - arm expansion to assess the safety, tolerability, PK, PD and efficacy of NT219, alone in adults with recurrent or metastatic solid t
Slide 22: IM1240: CD3x5T4xNKG2A Tri-Specific Antibody
Advancing First - in - Class Oncology Therapies IM1240: CD3x5T4xNKG2A Conditionally - Activated Tri - Specific Antibody
Slide 23: A Novel Mechanism of Action Tri-Specific Antibody
| 23 A Novel Mechanism of Action Tri - Specific Antibody 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 masking by proteases of the tumor microenvironment T
Slide 24: 5T4, a Novel Target in Oncology
5T4, 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 stratification st
Slide 25: Promising Proof of Concept Data
Promising Proof of Concept Data • Tribody induces sub - nM EC 50 against A549 cells • 20 - fold more potent than CD3x5T4 variant • Cell killing validated on multiple 5T4 + cell lines (MDA - MB - 231, HCT116, NCI - H226) • Sustained regressions in Breast Cancer xenograft model (MDA - MB - 231) • The
Slide 26: Corporate Highlights
Corporate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of June 30, 2023 • ADS Outstanding: 21.4 M • Cash Balance : $18 M Strong position to reach short and mid term value creating clinical data catalysts | 26 • Multiple data read - outs expected in 2023 & 2024 • Two First - in - Class clinical s
Slide 27: Contact Us / Thank You
| 27 Contact Us: ir@purple - biotech.com THANK YOU
Slide 28: Appendix A | CM24
Appendix A | CM24
Slide 29: 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 p
Slide 30: CM24 Safe and Well Tolerated in Combination with Nivolumab
Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combination with Nivolumab Total Grade 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 2 2 Co
Slide 31: CM24 Phase 1 Combination Study Demographics
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 determi
Slide 32: 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
Slide 33: CEACAM1 Plays a Key Role in Cancer Biology
CEACAM1 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 CEACAM1 as a putative therapeutic target to prevent metastatic progression of colon ca
Slide 34: Appendix B | NT219
Appendix B | NT219
Slide 35: Novel MOA: IRS Degradation By NT219
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 2 Ser - phosphorylation Degradation 3 Covalent binding to IRS1/2 leads to the dissociation of IRS1/2 from IGF1R Serine phosphorylation prevents re
Slide 36: NT219 Re-sensitizes Tumors Refractory to α-PD1
0 200 400 600 800 1000 1200 0 5 10 15 20 Tumor volume (mm3) Days following treatment initiation Control (n=3) NT219 (n=3) Keytruda (n=3) Keytruda + NT219 (n=3) Autologous PBMCs (2.1 M/mouse) NT219 Re - sensitizes Tumors Refractory to α - PD1 PDX Model Humanized PDX of GastroEsophageal Junction (GEJ)
Slide 37: Novel MOA: STAT3 Inhibition
| 37 Zou, S., Tong, Q., Liu, B. et al. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer 19, 145 (2020). https://doi.org/10.1186/s12943 - 020 - 01258 - 7 Novel MOA Signal Transducer and Activator of Transcription 3 (STAT3) Inhibition • Point of convergence for numerous oncogenic signaling pathways
Slide 38: Simultaneous Blockade of STAT3 and AKT Pathways
| 38 Simultaneous Blockade of STAT3 and AKT Pathways are Required to Overcome Resistance to EGFRi Overcoming drug resistance NT219 NT219 STAT3 IRS EGFR EGFRi MEK / ERK TUMOR REGRESSION Proof of Concept: PDX model of Head and Neck Cancer Control (n=6) Erlotinib (n=8) Erlotinib+NT219 (n=6) Erlotinib+R
Slide 39: NT219 Phase 1 Monotherapy Demographics
NT219 Phase 1 Dose Escalation Monotherapy Demographics As of data cutoff date of May 12th , 2022, a total of 14 patients were enrolled to 4 NT219 dose levels (3 - 24mg/kg) • 12 patients were evaluable for DLT determination including 4 CRC, 3 pancreatic cancer, 2 breast cancer, and one of each of the
Slide 40: Selected Publications
Selected Publications Michael Karin Alexander Levitzki Menashe Bar - Eli Michael Cox | 40
Slide 41: NT219 Suppresses β-Catenin Activity in CRC Cells
Colon cancer LS - 513 cells overexpressing IRS2 demonstrate enhanced - catenin activity. Targeted inhibition of IRS2 by NT219 or IRS2 - SH RNA, suppresses the increased - catenin activity and inhibit LS - 513 cell viability. Combination of 5 - FU and NT219 significantly inhibited the growth of CRC t
Slide 42: Pancreatic Cancer in Combination with Gemcitabine
PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar ® ) NT219 | Pancreatic Cancer in Combination with Gemcitabine | 42 Highly effective anti cancer activity exhibited by NT219 in combination with Gemcitabine
Slide 43: RNA Sequencing Analysis of Tumors Following Treatment
PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar®) RNA Sequencing | Analysis of Tumors Following Treatment Reduced expression of IRS1, Ki67, FOXM1 & TGFb is exhibited by pancreatic cancer treated with NT219 alone and in combination with gemcitabine | 43
Slide 44: Confirmed Partial Response as a Single Agent in a GEJ Cancer Patient
Confirmed Partial Response as a Single Agent in a GEJ Cancer Patient • In a patient with refractory GE junction disease (mutated KRAS, TP53), NT219 administration (3mg/kg as a single agent) was associated with a confirmed partial response (PR): • Complete remission at the largest target lesion (righ
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