Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (September 2023)
44 slides from Purple Biotech's investor presentation, September 2023
Slide 1: Corporate Presentation
CORPORATE PRESENTATION NASDAQ/TASE: PPBT September 2023 |1
Slide 2: Forward-looking Statements and Safe Harbor
Forward-looking Statements and Safe Harbor 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 forward-loo
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 2023 & 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of June 30, 2023 • A preclinical tri
Slide 4: Leadership Team
Leadership Team Eric K. Rowinsky, MD Gil Efron Lior Fhima Chairman of the Board Chief Executive Officer Chief Financial Officer Former CMO at ImClone, Stemline, Former Deputy CEO & CFO at Formerly at Kamada Board member at Biogen Inc. Kamada (NASDAQ:KMDA) (NASDAQ:KMDA) Michael Schickler, PhD Hadas R
Slide 5: 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 2H23 & CEACAM1 Pancreatic Cancer CM24* 1H24 mAb (+nivolumab+SoC) ❖ Phase 2 top line results 2H24 Solid tumors (monotherap
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
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 8: 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
Slide 9: 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 |9
Slide 10: 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 11.5%1 • Immuno-oncology approaches have been limited to patients with high microsatellite instability (MSI-H) or high tumor mutational burden (
Slide 11: 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 12: Phase 2 Combination Study Design (NCT04731467)
Phase 2 Combination Study Design (NCT04731467) Primary endpoint : Interim analysis: Measurement of A study of CM24 in combination - PFS 2H23 CEACAM1 and with nivolumab plus OS other bio-markers chemotherapy in PDAC patients in Secondary endpoints: - OS 1H24 is ongoing 2L treatment Top line data: PFS
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 and Beyond
NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond Novel • NT219 is a First-in-Class small molecule • Dual inhibitor of IRS1/2 and STAT3, two major drivers of resistance MOA to cancer therapies Robust • Significant efficacy in multiple in-vivo models preclinical • Modulation of the
Slide 15: NT219 blocks 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: Strong Efficacy in Monotherapy
Strong Efficacy in Monotherapy Animal model Head & Neck Cancer (SCC-9) NSG™, immuno- competent Drugs α-PD1 Cetuximab • NSG mice were injected SC with SCC-9 cells. NT219 • PBMCs (18*106 cells per mouse) administered 4 weeks prior to first treatment. • NT219 (IV), α-PD1 (IP), and cetuximab (IP) were a
Slide 17: 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 18: 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 19: NT219 Phase 1 Dose Escalation Monotherapy: Interim Results
NT219 Phase 1 Dose Escalation Monotherapy Interim Results Study Design Safety • No DLTs were observed across all dose levels. • As of data cutoff date of May 12th, 2022, a total of 14 • Nine Grade 3 adverse events (AEs) were observed, two of patients were enrolled and 12 patients were evaluable whic
Slide 20: NT219 Phase 1 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 BOR Cancer Type (prior lines) response included one confirmed Partial Response (gastroesophageal junction (GEJ) patient, > 5.5 months duration of response fol
Slide 21: NT219 Monotherapy and Combination Phase 1/2 Study Design
NT219 Monotherapy and Combination Phase 1/2 Study Design (NCT04474470) Study Title Endpoints A Phase 1/2 study with open-label, dose escalation phase Primary endpoints: followed by single-arm expansion to assess the safety, Safety, pharmacokinetics and to determine the tolerability, PK, PD and effic
Slide 22: Advancing First-in-Class Oncology Therapies: IM1240
Advancing First-in-Class Oncology Therapies IM1240: CD3x5T4xNKG2A Conditionally-Activated Tri-Specific Antibody
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: 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 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 sub-nM EC50 against A549 cells • Sus
Slide 26: 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 2023 & 2024 Purple Biotech (NASDAQ/TASE: PPBT) • Two First-in-Class clinical stage drugs As of June 30, 2023 • A preclinical tri
Slide 27: Thank You
THANK YOU Contact Us: ir@purple-biotech.com | 27
Slide 28: Appendix A | CM24
ce foe i ~©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 post
Slide 30: 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 31: 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 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 Respo
Slide 33: 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 34: Appendix B | NT219
Appendix B | NT219
Slide 35: 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 36: 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 37: 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 38: 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 39: NT219 Phase 1 Dose Escalation Monotherapy: Demographics
NT219 Phase 1 Dose Escalation Monotherapy Demographics As of data cutoff date of May 12th , 2022, a total Demographics of patients treated with NT219 (3, 6, 12, 24mg/kg) of 14 patients were enrolled to 4 NT219 dose Median age, years (range) 67 (39-79) Diagnosis , n (%) levels (3 - 24mg/kg) Sex, n (%
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
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 Baseline sca
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