Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (June 2022)
41 slides from Purple Biotech's investor presentation, June 2022
Slide 1: Corporate Presentation
CORPORATE PRESENTATION NASDAQ/TASE: PPBT June 2022 |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: Business Highlights
Business Highlights We are a clinical-stage company committed to the development of first-in-class, effective therapies by harnessing the power of the tumor microenvironment (TME) to overcome drug resistance and improve treatment outcomes for cancer patients • Two first-in-class drug candidates Stro
Slide 4: Harnessing the Power of the TME
Harnessing the Power of the TME • Hammering cancer cells is not sufficient (i.e, chemotherapy, radiotherapy) • Tumors rely on a favorable environment to strive and escape the Immune surveillance • Multiple resistance mechanisms prevent long-term survival • Concept fully validated with the rise of Im
Slide 5: A Pipeline Dedicated to Advancing Oncology Therapies
A Pipeline Dedicated to Advancing Oncology Therapies Program Indication Phase 1 Phase 2 Phase 3 Value Drivers Solid tumors (monotherapy) Completed √ RP2D in combination: 20 mg/kg √ Initiation of phase II in 2L PDAC Solid tumors (combination with nivolumab*) CM24 Pancreatic Cancer (combination with n
Slide 6: Advancing First-in-Class Oncology Therapies CM24: an α-CEACAM1 mAb
Advancing First-in-Class Oncology Therapies CM24: an α-CEACAM1* mAb *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 • CM24 inhibits the immunosuppressive effect of CEACA
Slide 8: 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 9: CM24 MOA | Immuno-Oncology & Adhesion
CM24 MOA | Immuno-Oncology & Adhesion Tumor Neutrophil extracellular trap-associated CEACAM1 as a putative therapeutic target to prevent metastatic progression: CEACAM1 CEACAM5 Primary Tumor Metastasizing CEACAM1 CEACAM1 CM2 CD8+T & NK Cells 4 Metastatic Activation of Tumor enhanced cytotoxic activi
Slide 10: 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 11: CEACAM1 is Highly Over-Expressed in PDAC
CEACAM1 is Highly Over-Expressed in PDAC 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 | 11
Slide 12: 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 13: CM24 Phase 1 Dose Escalation Interim Results (cont.)
CM24 Phase 1 Dose Escalation Interim Results (cont.) Sustained Clinical Benefit Even After Treatment Cessation For the 11 evaluable patients as of March 8th, 2022, best Overall Survival overall response included 1 confirmed PR (PDAC patient) 3 SD (2 PDAC and 1 PTC) for a disease control rate of 36%
Slide 14: 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 15: Large Market Opportunity in Pancreatic Cancer
Large Market Opportunity in Pancreatic Cancer • Pancreatic Cancer accounts for ~60K new cases/year in the US; with a 5-year relative survival rate of 10%1 • I/O approaches have been limited to patients with high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H) • 5-year over
Slide 16: CM24 Phase 2 Combination Study Design (NCT04731467)
CM24 Phase 2 Combination Study Design (NCT04731467) A Phase 2 open-label multicenter study Primary efficacy endpoint: Measurement of CEACAM1 based of CM24 in combination with: ORR bio-marker • Nivolumab and 5-fluorouracil and liposomal Secondary endpoints: irinotecan or nab-paclitaxel in 2L pancreat
Slide 17: 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
Slide 18: NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond
NT219 - A Novel Approach to Overcome Resistance to EGFRi and Beyond 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 • Modulation of the tumor microenviron
Slide 19: NT219 - Dual Inhibitor of IRS1/2 & STAT3
NT219 - Dual Inhibitor of IRS1/2 & STAT3 IRS1/2 • Scaffold proteins, mediating mitogenic, metastatic, angiogenic and anti-apoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumors STAT3 • Regulates major survival pathways such as • Well-established transcription fa
Slide 20: 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 21: 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 play
Slide 22: 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 23: NT219 Efficacy as Monotherapy
NT219 Efficacy as Monotherapy Animal model Head & Neck Cancer (SCC-9) NSG™, PBMCs- injected1 Drugs α-PD1 Cetuximab (Erbitux®) NT219 20mg/kg NT219 60mg/kg 1 NSG mice were injected SC with SCC-9 cells. PBMCs were injected to the mice (18M cells per mouse) and treatments initiated when tumors were esta
Slide 24: NT219 Restores Sensitivity to EGFRi in PDX Models
* NT219 Restores Tumor Volume (mm3) 2,000 Sensitivity to 1,500 EGFRi in PDX 1,000 500 Models 0 Control NT219 Osimertinib Osimertinib+NT219 Osimertinib 5 mg/kg, NT219 65 mg/kg, mean tumor volume at the end point, 3 mice/group; NSCLC Exon 19 deletion EGFR and T790M, biopsy of bone ** marrow metastasis
Slide 25: NT219 Resensitizes Tumors Refractory to α-PD1
NT219 1200 Resensitizes 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®) Day
Slide 26: 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 27: 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 line) response included one confirmed PR (GEJ patient, > 5.5 months duration of response following end of treatment), and 3 SD with on
Slide 28: Confirmed PR as Single Agent in a GEJ Cancer Patient
Confirmed PR as 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 (right) Baseline scan
Slide 29: First Market Opportunity
First Market Opportunity Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) Targeting the unmet medical need • 1L Standard of care has shifted from chemotherapy towards immuno-oncology + chemotherapy • < 20% of R/M SCCHN patients respond to Pembrolizumab • SCCHN is the 6th most
Slide 30: 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 MTD tolerability, PK, PD and e
Slide 31: Business Highlights
Business Highlights We are a clinical-stage company committed to the development of first-in-class, effective therapies by harnessing the power of the tumor microenvironment (TME) to overcome drug resistance and improve treatment outcomes for cancer patients • Two first-in-class drug candidates Stro
Slide 32: Thank You
THANK YOU We are committed to provide cancer patients with first-in-class therapies to OVERCOME tumor drug resistance, ENHANCE treatment response and SLOW tumor progression Contact Us: ir@purple-biotech.com | 32
Slide 33: Appendix A | CM24
Appendix A | CM24
Slide 34: PK/PD Modeling Provides Dosage & Schedule Guidance
PK/PD Modeling Provides Dosage & Schedule Guidance • CM24 completed Phase 1 monotherapy open-label, Simulated TMDD1 saturation dose-escalation study to assess safety and tolerability at Ctrough2 with Q2W regimen • Heavily pre-treated 24 evaluable patients with a median of 4 prior regimens • Overall,
Slide 35: 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 36: Appendix B | NT219
Appendix B | NT219
Slide 37: Selected Publications
Selected Publications Michael Alexander Karin Levitzki Menashe Michael Bar-Eli Cox | 37
Slide 38: 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 (Relati
Slide 39: Highly effective anti cancer activity exhibited by NT219
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®) | 39
Slide 40: 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®) | 40
Slide 41: 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 (%