Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (March 2024)
43 slides from Purple Biotech's investor presentation, March 2024
Slide 1: Corporate Presentation
CORPORATE PRESENTATION NASDAQ/TASE: PPBT March 2024 |1
Slide 2: Forward-looking Statements and Safe Harbor
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 forward-look
Slide 3: Corporate Highlights
Corporate Highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Multiple data read-outs expected in 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of December 31, 2023 • A preclinical tri-sp
Slide 4: A Pipeline Dedicated to Advancing Oncology Therapies
A Pipeline Dedicated to Advancing Oncology Therapies Project Target Indications Development Stage Value Drivers Pre-Clinical Phase I Phase II Phase III ❖ Phase 2 interim analysis 1H24 CEACAM1 Pancreatic Cancer CM24* ❖ Phase 2 top line mAb (+nivolumab+SoC) results 2H24 Solid tumors (monotherapy) STAT
Slide 5: 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 6: CM24: a New Multi-Functional Immune Checkpoint Inhibitor
CM24: a New Multi-Functional Immune Checkpoint Inhibitor • CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells Attractive new target • CEACAM1 interacts with CEACAM1 and CEACAM5 and creates a tumor-protective environment Demonstrated • CM24 increases T cell and NK cells cyt
Slide 7: CM24 MOA Immune Check Point Inhibitor & Anti-Metastatic Activity
CM24 MOA Immune Check Point Inhibitor & Anti-Metastatic Activity A. Immune Response Activation B. CM24 Suppresses Neutrophil Extracellular Trap (NET)-Induced Migration and Metastasis of Cancer Cells Primary Tumor Metastasizing Tumor CM24 CEACAM1 CEACAM5 Metastatic Tumor CM24 Direct Binding of CM24 t
Slide 8: CEACAM1 is Over-Expressed in Pancreatic Cancer
CEACAM1 is Over-Expressed in Pancreatic Cancer Comparison between CEACAM1 staining Representative examples of CEACAM1 immunohistochemical images of pancreatic intensity in pancreatic cancer (38 cases/76 cores) adenocarcinoma and normal tissues and normal (10 cases/20 cores) tissues |8
Slide 9: Large Market Opportunity in Pancreatic Cancer
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 burden (TM
Slide 10: CM24 Phase 1 Dose Escalation Results
CM24 Phase 1 Dose Escalation Results Encouraging data in 2L/3L Pancreatic Ductal Adenocarcinoma (PDAC) patients Study Results 14 patients were evaluable for efficacy: SD PR • Best overall response included 1 Partial SD Response (PR) (PDAC) and 4 Stable Disease (SD) (3 PDAC and 1 papillary thyroid ca
Slide 11: Identification of potential exploratory biomarkers supporting CM24's mechanism
Phase 1 study results (cont.): Identification of potential exploratory biomarkers supporting CM24’s mechanism of action Higher pre-treatment levels of tumor infiltrating lymphocytes CM24 treatment significantly reduced NET marker in serum that express CEACAM1 are associated with longer survival • co
Slide 12: Phase 2 Combination Study Design (NCT04731467)
Phase 2 Combination Study Design (NCT04731467) A study of CM24 in combination Primary endpoint : Interim analysis: 1H24 Measurement of with nivolumab plus OS Top line data: 2H24 CEACAM1 and chemotherapy in PDAC patients in other bio-markers Secondary endpoints: 2L treatment is ongoing PFS, OS rate @
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 new solution to improve treatment outcome for cancer patients
NT219, a new solution to improve treatment outcome for cancer patients Innovative • NT219 is a First-in-Class, small molecule MOA • Dual inhibitor of IRS1/2 and STAT3 Robust • Outstanding efficacy in various PDX models in monotherapy and in combination preclinical • Uniquely positioned to tackle res
Slide 15: NT219 blocks 2 critical signalling pathways at once
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 STAT3 multiple tumors • Well-established transcription factor • Regulates major survival
Slide 16: NT219 Restores Sensitivity to EGFRi in PDX Models
* Tumor Volume (mm3) 2,000 NT219 Restores 1,500 Sensitivity to EGFRi 1,000 in PDX Models 500 0 Control NT219 Osimertinib Osimertinib+NT219 Lung Cancer Osimertinib 5 mg/kg, NT219 65 mg/kg, mean tumor volume at the end point, 3 mice/group; Non-small cell lung cancer (NSCLC) Exon 19 deletion EGFR and T
Slide 17: NT219 induces PDL1 and re-sensitizes aPD1-refractory model
NT219 induces PDL1 and re-sensitizes aPD1-refractory model NT219+aPD1 reverse resistant tumors NT219 induces PDL1 expression 2000 Control (n=10) Control α-PD-1 (n=10) aPD1-resistant melanoma α-PD-1 NT219 (n=10) cells (FACS analysis) Tumor volume (mm3) NT219 1500 NT219+α-PD-1 (n=10) NT219+α-PD-1 ✱✱✱✱
Slide 18: NT219 combination with aPD1 achieves a profound reprograming of the TME
NT219 combination with αPD1 achieves a profound reprograming of the TME NT219+aPD1 leads to a significant increase in NT219+aPD1 leads to a significant reduction in cytotoxic effector cells (T & NK cells) myeloid derived suppressor cells (MDSC) cells (% CD8+GZMB +) Activated cytotoxic T (out of CD45
Slide 19: First Market Opportunity
First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Targeting the unmet medical need • SCCHN is the 6th most common cancer type ; 175k new cases/year are expected by 2024 • 1L standard of care has shifted from chemotherapy towards immuno-oncology + chemo
Slide 20: Phase 1 dose escalation in combination with cetuximab
Phase 1 dose escalation in combination with cetuximab: Well tolerated, target exposure reached, patient’s responses observed • No DLTs reported, NT219 was well tolerated as monotherapy and in combination with cetuximab • Dose-proportional increase in AUC and Cmax values • Human Equivalent Dose expos
Slide 21: Phase 1 Dose Escalation: Anti-tumor activity at target exposure level
Phase 1 Dose Escalation (cont.): Anti-tumor activity at target exposure level, 2 confirmed responses in SCCHN patients Efficacy overview of monotherapy arm: • 20 evaluable patients (all doses): 2 PR (confirmed-GEJ, unconfirmed-PDAC), 5 SD Best % change from baseline Efficacy overview of combination
Slide 22: Advancing First-in-Class Oncology Therapies: Tri-Specific Antibody Platform
Advancing First-in-Class Oncology Therapies Conditionally-Activated Tri-Specific Antibody Platform Lead candidate: IM1240 (CD3x5T4xNKG2A)
Slide 23: A Novel Mechanism of Action Tri-Specific Antibody
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 features: • D
Slide 24: Unleashing both Innate and Adaptive Immune Systems
Unleashing both Innate and Adaptive Immune Systems NK-cells CD4+-T-cells CD8+-NKG2A+-T-cells NK cell activation by CD4+-T-cells activation CD8+-NKG2A+ T-cells inhibition of HLAE- through CD3 binding double activation through NKG2A/CD94 binding CD3 binding and NKG2A- HLA-E axis blocking | 24
Slide 25: Promising Proof of Concept Data
Promising Proof of Concept Data Increased cytotoxicity with Cleavable Control tribody format capping leads to Non-cleavable Cap improved in vivo efficacy CD3x5T4xNKG2A CD3x5T4 No Cap EC50 tribody: 0.003 nM EC50 bispecific: 0.066 nM Cleavable Cap • Tribody induces pM EC50 against A549 cells • Sustain
Slide 26: 5T4: a Novel Target in Oncology
5T4: a Novel Target in Oncology 5T4 is highly expressed on certain tumors 5T4 is a Tumor Associated Antigen and correlates with poor prognosis prevalent to several large indications Am J Cancer Res 2018;8(4):610-623 www.ajcr.us /ISSN:2156-6976/ajcr0074519 Opportunity of patient stratification strate
Slide 27: Corporate Highlights
Corporate Highlights Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need • Multiple data read-outs expected in 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of December 31, 2023 • A preclinical tri-sp
Slide 28: Thank You
THANK YOU Contact Us: ir@purple-biotech.com | 28
Slide 29: Appendix A | CM24
ce foe i ~©Appendix A | CM24
Slide 30: CEACAM1 Plays a Key Role in Cancer Biology
CEACAM1 Plays a Key Role in Cancer Biology 01 | ADHESION 02 | IMMUNE CELLS/ 03 | IMMUNO-ONCOLOGY IMMUNE EXCLUSION Horst, 2011 Tsuzuki, 2020 Blumberg, 2015 “CEACAM1 creates a pro-angiogenic “Immune‐checkpoint molecules on “CEACAM1 regulates tumor microenvironment that regulatory T‐cells as a potentia
Slide 31: 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 post
Slide 32: Phase 1 Dose Escalation Interim Results
Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combination with Nivolumab Study Design Safety • As of March 8th, 2022, a total of 13 patients were enrolled and 11 • No DLTs were observed across all dose levels; no Grade 4 patients were evaluable for DLT determination (8 P
Slide 33: CM24 Phase 1 Combination Study (NCT04731467)
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. Demographics of patients treated with CM24 (10, 15, 20mg/kg) • The primary objective of this part was t
Slide 34: 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 Respo
Slide 35: Appendix B | NT219
Appendix B | NT219
Slide 36: Novel MOA: IRS Degradation By NT219
Novel MOA: IRS Degradation By NT219 Blocking IGF1R-AKT Pathway1 1 Binding to IRS 2 Ser-phosphorylation 3 Degradation IGF1 IGF1R IGF1 IGF1 IGF1 IGF1R IGF1R IGF1R IRS NT pS PI3K IRS IRS pS AKT AKT AKT AKT CANCER CELL SURVIVAL CANCER CELL APOPTOSIS Covalent binding to IRS1/2 leads to the Serine phospho
Slide 37: NT219 Re-sensitizes Tumors Refractory to α-PD1
NT219 1200 Re-sensitizes Control (n=3) NT219 (n=3) Tumors Refractory 1000 Keytruda (n=3) to α-PD1 Keytruda + NT219 (n=3) Tumor volume (mm3) 800 PDX Model 600 Humanized PDX of GastroEsophageal Junction 400 (GEJ) Cancer (refractory to pembrolizumab) 200 Drug Pembrolizumab 0 0 5 10 15 20 (Keytruda®) Da
Slide 38: Novel MOA: STAT3 Inhibition
Novel MOA Signal Transducer and Activator of Transcription 3 (STAT3) 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 ecosystem and plays
Slide 39: Simultaneous Blockade of STAT3 and AKT
Simultaneous Blockade of STAT3 and AKT Pathways are Required to Overcome Resistance to EGFRi Overcoming drug resistance Proof of Concept: PDX model of Head and Neck Cancer Erlotinib Control (n=6) Erlotinib (n=8) EGFRi Erlotinib+NT219 (n=6) EGFR Erlotinib+Ruxolitinib (n=6) EGFR Erlotinib+Buparlisib (
Slide 40: Selected Publications
Selected Publications Michael Alexander Karin Levitzki Menashe Michael Bar-Eli Cox | 40
Slide 41: NT219 Suppresses β-Catenin activity in CRC Cells
NT219 Suppresses β-Catenin activity in CRC Cells and Inhibited CRC Brain Metastasis In Vitro In Vivo 5-FU Silencing IRS2 inhibits NT219 downregulates IRS2 and suppresses the b-catenin activity CRC Cell Viability (72hr) b-catenin activity DMEM β-catenin luciferase activity 1.5 *** iAKT DMEM (Relative
Slide 42: NT219 Pancreatic Cancer in Combination with Gemcitabine
NT219 | Highly effective anti cancer activity exhibited by NT219 Pancreatic Cancer in combination with Gemcitabine in Combination with Gemcitabine PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar®) | 42
Slide 43: RNA Sequencing Analysis of Tumors Following Treatment
Reduced expression of IRS1, Ki67, FOXM1 & TGFb is RNA Sequencing | exhibited by pancreatic cancer treated with NT219 alone and Analysis of Tumors in combination with gemcitabine Following Treatment PDX model Pancreatic Cancer Drug Gemcitabine (Gemzar®) | 43