Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Investor Presentation (March 2024)
43 slides from Purple Biotech's investor presentation, Mar 6, 2024
Slide 1: Corporate Presentation March 2024
| 1 NASDAQ/TASE: PPBT March 2024 CORPOR A TE PRESEN T A TION
Slide 2: Forward-looking Statements and Safe Harbor
Fo r war d - lo o kin g Sta t em e nt s and Safe Harbor | 2 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 19
Slide 3: Corporate Highlights
Corpo r ate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of December 31, 2023 • ADS Outstanding: 25.2 M • Cash Balance: $15.3 M Str on g p osi t io n t o reac h sho r t and m i d t erm valu e creat i n g clinical data catalysts | 3 • Multiple data read - outs expected in 2024 • Two First - in -
Slide 4: A Pipeline Dedicated to Advancing Oncology Therapies
A Pipeline Dedicated to Advancing Oncology Therapies *Clinical collaboration and supply agreement with: Multi p l e data r ea d - outs ex p ecte d i n the nex t 12 months Value Drivers Development Stage Indications Target Project Phase III Phase II Phase I Pre - Clinical □ Phase 2 interim analysis 1
Slide 5: Advancing First-in-Class Oncology Therapies: CM24
Advancing Firs t - i n - Class Oncolog y Therapies CM24: an α - CEACAM1* mAb Lead indication : Pa n creat i c Ductal Ade n ocarcinom a (PDAC) *Carcinoembryonic Antigen Cell Adhesion Molecule
Slide 6: CM24: a New Multi-Functional Immune Checkpoint Inhibitor
| 6 C M 24 : a N e w 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 ne w targ e t • CM24 increases T cell and NK cells
Slide 7: CM24 MOA: Immune Check Point Inhibitor & Anti-Metastatic Activity
| 7 CM24 MOA Immune Check Point Inhibitor & Ant i - M e tas tati c Ac t ivity 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.; Ray
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 Oppor t u n it y i n 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 muta
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: • Best overall response included 1 Partial Response (PR) (PDAC) and 4 Stable Disease (SD) (3 PDAC and 1 papillary thyroid cancer (PTC
Slide 11: Phase 1 Study Results: Potential Exploratory Biomarkers
Phase 1 study results (cont.): Identification of potential exploratory b i omark e r s su pporting CM 24 ’ s m ech a n i s m o f ac t ion Higher pre - treatment levels of tumor infiltrating lymphocytes that express CEACAM1 are associated with longer survival • consistent with the CM24 MoA in suppres
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 - ma r k e r s i
Slide 13: Advancing First-in-Class Oncology Therapies: NT219
Advancing Firs t - i n - Class Oncolog y Therapies NT219: A Small Mol e cule Dual Inhibitor o f IRS 1/2 and S T A T3 Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)
Slide 14: NT219, a New Solution to Improve Treatment Outcome
| 14 N T 219 , a ne w soluti o n t o improv e tr e atment outc o me for cancer patients • NT219 is a First - in - Class , small molecule • Dual inhibitor of IRS1/2 and STAT3 I nn o v a ti v e MOA • Outstanding efficacy in various PDX models in monotherapy and in combination • Uniquely positioned to
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 PI3K/AKT, MEK/ERK a
Slide 16: NT219 Restores Sensitivity to EGFRi in PDX Models
| 16 NT 21 9 Res t o r es Sensitiv i t y t o E G FRi i n 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 carc
Slide 17: NT219 Induces PDL1 and Re-sensitizes aPD1-Refractory Model
| 17 NT219 induces PDL1 and re - sensitizes aPD1 - refractory model 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 Days following tumor challenge 0 50 0 100 0 150 0 200 0 Tu m o r v o l um e ( m m 3 ) Control (n=10) α - PD - 1 (n=10) NT219 (n=10) NT 219 + α - P D - 1 (n =10) PD1 - resistant melanoma cells (FACS an
Slide 18: NT219 Combination with aPD1 Reprograms the TME
| 18 N T 21 9 combination with α PD 1 achiev e s a p r ofound r e pr o gr a m i n g o f the TME NT219 and aPD1 combination converted immuno - suppressive TME t o im m uno - re active * Collaboration with Prof. Bareli and Prof. Curran, M.D. Anderson cancer center, presented at AACR 2023 Activated cyt
Slide 19: First Market Opportunity: Recurrent or Metastatic SCCHN
| 19 Fir s t Market Opportu n i ty 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 glob
Slide 20: Phase 1 Dose Escalation in Combination with Cetuximab
| 20 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 D
Slide 21: Phase 1 Dose Escalation: Anti-tumor Activity at Target Exposure
| 21 Efficacy overview of monotherapy 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 22: Advancing First-in-Class Oncology Therapies: IM1240
Advancing Firs t - i n - Class Oncolog y Therapies Conditionall y - Activat e d T ri - Sp e cific Antibody Platf o rm Lead candidate: IM1240 (CD3x5T4xNKG2A)
Slide 23: A Novel Mechanism of Action
| 23 A Nov e l Me c hanis m o f Acti o n T r i - Sp e cific Antibody C a ncer bin d e r a - T A A A bs a - NK bin d e r A bs T - cell - binder a - CD 3 A bs aCD3 masking moiety Tumor cell T cell N K ce ll Cancer microenvironment P r o t ea s e cl eava g e Removal of T cell engager’s masking by prote
Slide 24: Unleashing both Innate and Adaptive Immune Systems
| 24 N K - c ells CD4 + - T - cells CD8 + - NKG2A + - T - cells NK cell activation by inhibition of HLAE - NKG 2 A/CD 94 binding CD4 + - T - cells activation through CD3 binding CD8 + - NKG2A + T - cells double activation through CD3 binding and NKG2A - HLA - E axis blocking Unleashing both Innate a
Slide 25: Promising Proof of Concept Data
| 25 Promising Proof o f Conce p t Data • Tribody induces pM 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 tumor regressions in Breast Cancer xenograft humanized model (MDA
Slide 26: 5T4: a Novel Target in Oncology
5 T 4 : a N o ve l T ar g e t i n Oncolo g y 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 stra
Slide 27: Corporate Highlights
Corpo r ate Highlights Purple Biotech (NASDAQ/TASE: PPBT) As of December 31, 2023 • ADS Outstanding: 25.2 M • Cash Balance: $15.3 M Str on g p osi t io n t o reac h sho r t and m i d t erm valu e creat i n g clinical data catalysts | 27 • Multiple data read - outs expected in 2024 • Two First - in -
Slide 28: Contact Us / Thank You
| 28 Co n tac t Us: i r @p u rp le - b i otec h . com TH A NK YOU
Slide 29: Appendix A | CM24
Appe n d i x A | CM24
Slide 30: CEACAM1 Plays a Key Role in Cancer Biology
CEACAM1 Plays a K e y Role i n Cancer Biolo g y 0 1 | AD H ES I O N 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
Slide 31: CM24 Reduces Tumor Burden & Synergetic with a-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 32: Phase 1 Dose Escalation Interim Results: CM24 Safe and Well Tolerated
Phase 1 Dose E scalatio n Int e ri m 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
Slide 33: CM24 Phase 1 Combination Study Demographics
CM24 Phase 1 Combination Study ( NCT0 4 7314 6 7) 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 34: Confirmed Partial Response in a 3L PDAC Patient
Confirm e d Partial Re s pon se i n a 3L PDAC Pati e nt 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
Slide 35: Appendix B | NT219
Appe n d i x B | NT2 1 9
Slide 36: Novel MOA: IRS Degradation by NT219
No v e l MO A : IRS Deg r adation By NT2 1 9 Blocki n g I G F1 R - AKT Pathwa y 1 Binding to IRS 1 1 Reuveni et al. Cancer Res 2013 ; Ibuki et al. Mol Cancer Ther 2014 2 Ser - phosphorylation Degrad a ti on 3 Covalent binding to IRS1/2 leads to the dissociation of IRS1/2 from IGF1R Serine phosphoryl
Slide 37: NT219 Re-sensitizes Tumors Refractory to a-PD1 PDX Model
0 2 00 4 00 6 00 8 00 1 0 0 0 1 2 0 0 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 T u m or s Refra cto r y t o α - PD 1 PDX Model Humanized PDX of GastroEsopha
Slide 38: Novel MOA: STAT3 Inhibition
| 38 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 No v e l MOA Signal Transducer and Activator of Transcription 3 (STAT3) Inhibition • Point of convergence for numerous oncogenic signaling pathw
Slide 39: Simultaneous Blockade of STAT3 and AKT Pathways Overcomes EGFRi Resistance
| 39 Simultaneous Blockade of STAT3 and AKT Pat h wa ys are Req u i re d t o O v e rcom e Re s i s ta n ce t o EGFRi Overcoming drug resistance NT219 NT219 S T A T 3 IRS E G F R E G F Ri MEK / ERK TUMOR R E GR E SS ION Proof of Concept: PDX model of Head and Neck Cancer Control (n=6) Erlotinib (n=8)
Slide 40: Selected Publications
Selected Publ i ca t ions Mich a el Karin A l ex a n der Levitzki Menashe Bar - Eli Michael Cox | 40
Slide 41: NT219 Suppresses b-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 | P a ncreat i c 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®) RN A Seq u enc i n g | Analysis of Tumors Fo l lo w ing Treatment Reduced expression of IRS1, Ki67, FOXM1 & TGFb is exhibited by pancreatic cancer treated with NT219 alone and in combination with gemcitabine | 43