Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Kitov Pharma — Investor Presentation (November 2020)
39 slides from Purple Biotech's investor presentation, Nov 12, 2020
Slide 1: Corporate Presentation | November 2020
1 CORPORATE PRESENTATION | NOVEMBER 2020
Slide 2: Forward-Looking Statements and Safe Harbor
2 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 for
Slide 3: Our Transformation into Oncology
3 OUR TRANSFORMATION INTO ONCOLOGY 2020 2017 2013 2018 2017 2015 2011 2019 Established TASE listing CONSENSI® Phase III positive results & NASDAQ IPO CONSENSI® NDA submission CONSENSI® NDA approval & China partnership Acquisition of TyrNovo / NT 219 Acquisition of FameWave / CM24 NT219 – Phase 1/2 i
Slide 4: Advancing clinical-stage novel oncology therapies
4 Advancing clinical - stage novel oncology therapies x CM 24 - First - in - class α - CEACAM 1 mAb , clinical collaboration with x NT 219 - First - in - class, small molecule, dual inhibitor of IRS 1 / 2 and STAT 3 x H 2:21 - Two phase 1 study readouts x Strong balance sheet and cash position Marke
Slide 5: Expanding Pipeline
5 EXPANDING PIPELINE Multiple data read - outs expected in the next 12 months Program Indication Preclinical Phase 1 Phase 2 Phase 3 Partner Value Drivers CM 24 (CEACAM - 1 ) Solid tumors (monotherapy) Solid tumors (combination with nivolumab ) Initiation: Q4:20 Topline : H2:21 NSCLC (combination wi
Slide 6: Experienced Leadership
6 6 Eric K. Rowinsky, MD Chairman of the Board Former CMO at ImClone, Stemline, Board member at Biogen Inc. Isaac Israel Chief Executive Officer Former CEO of BeeContact Ltd. (TASE:BCNT), NextGen Biomed (TASE: NXGN) Bertrand Liang, MD, PhD, MBA, AMP Chief Medical Officer Formerly at Biogen Idec, Amg
Slide 7: Advancing First-in-Class Oncology Therapies: CM24
7 Advancing First - in - Class Oncology Therapies CM24 - an α - CEACAM1 mAb
Slide 8: CEACAM1 role in immuno-oncology
8 ADHESION: IMMUNE CELLS/IMMUNE EXCLUSION: IMMUNO - ONCOLOGY: “ CEACAM1 creates a pro - angiogenic tumor microenvironment that supports tumor vessel maturation ” Horst, 2011 “ Neutrophil extracellular trap - associated CEACAM1 as a putative therapeutic target to prevent metastatic progression of col
Slide 9: CM24: Selective Blocking of CEACAM1
9 CM24: SELECTIVE BLOCKING OF CEACAM1 IgG4 humanized monoclonal antibody, similar to anti - PD - 1 IO agents (no elicitation of ADCC or CDC) Nanomolar efficiency of binding to extracellular domain of CEACAM1 Anticipated to impact triple mechanisms of action of CEACAM1 in the neoplastic phenotype
Slide 10: Preclinical data with CM24 + TIL and CM24 + anti-PD1
10 Xenograft, lung lesion, Mel 526 (IV) Tumor burden was monitored 26 days post last CM24 treatment TIL + IgG TIL + CM 24 Naïve Combination index ( CI) = 0.15 < 1 synergy ANTI - CANCER EFFECT FOLLOWING TREATMENT PRECLINICAL DATA WITH CM24 + TIL AND CM24 + α - PD1 Significant benefits as both single
Slide 11: CM24 Phase 1 Monotherapy Trial
11 CM 24 PHASE 1 MONOTHERAPY TRIAL Open - label, multi - dose escalation monotherapy study to assess safety and tolerability Heavily pre - treated patients with a median of 3 prior regimens (range 2 - 8) and a median of 4 prior regimens at the 3mg/kg & 10mg/kg Overall, treatment was well tolerated M
Slide 12: PK/PD Modeling Provides Dosage & Schedule Guidance
12 PK/PD MODELING PROVIDES DOSAGE & SCHEDULE GUIDANCE Simulated TMDD 1 saturation at Ctrough with Q2W regimen Predictions with Q 3 W regimen Modeling with increased interval between doses demonstrates lower TMDD at 10 mg/kg dose With Q 3 W, 20 mg/kg dosing is not sufficient for saturation across pop
Slide 13: Large Market Opportunity: NSCLC & Pancreatic Cancer
13 LARGE MARKET OPPORTUNITY | NSCLC & PANCREATIC CANCER CEACAM1 expression correlates with poor prognosis in NSCLC and Pancreatic cancer 1 Preclinical data supports significant synergy Receptor saturation with CM24 is better achieved with a Q2W regimen, aligning with the nivolumab schedule Combining
Slide 14: CM24 Phase 1/2 Combination Study Design
14 CM 24 PHASE 1 / 2 COMBINATION STUDY DESIGN 13 A Phase 1 / 2 open label multi center study of CM 24 in combination with: Nivolumab in selected cancer indications (Phase 1 ) and NSCLC (Phase 2 ) Nivolumab and nab - paclitaxel in Pancreatic cancer (Phase 2 ) Measurement of CEACAM 1 based bio - marke
Slide 15: Advancing First-in-Class Oncology Therapies: NT219
15 Advancing First - in - Class Oncology Therapies NT 219 – A Dual Inhibitor of IRS 1 / 2 and STAT 3
Slide 16: NT219 Dual Inhibitor of IRS1/2 & STAT3
16 16 NT 219 - DUAL INHIBITOR OF IRS 1 / 2 & STAT 3 IRS 1 / 2 STAT3 Scaffold proteins, mediating mitogenic , metastatic, angiogenic and anti - apoptotic signals from IGF 1 R, IR, IL 4 R and other oncogenes, overexpressed in multiple tumor types 1 Regulates major survival pathways such as the PI 3 K/
Slide 17: Novel MOA: IRS Degradation by NT219
17 1 Reuveni et al. Cancer Res 2013 NOVEL MOA: IRS DEGRADATION BY NT 219 BLOCKING IGF 1 R - AKT PATHWAY 1 17 Covalent binding to IRS1/2 leads to the dissociation of IRS1/2 from IGF1R Serine phosphorylation prevents re - binding of IRS 1 / 2 to the receptor Ser - phosphorylation Binding to IRS 02 01
Slide 18: NT219 Efficacy as Monotherapy
18 NT 219 | EFFICACY AS MONOTHERAPY 18 Animal model Head & Neck Cancer (SCC - 9 ) NSG Ρ , PBMCs - injected 1 Drugs α - PD 1 Cetuximab (Erbitux®) NT 219 20 mg/kg NT 219 60 mg/kg 1 NSG mice were injected SC with SCC - 9 cells . PBMCs ( 18 * 10 6 cells per mouse) administered 4 weeks prior to first tre
Slide 19: STAT3 and IRS Are Essential in Therapeutic Resistance
19 STAT 3 AND IRS ARE ESSENTIAL IN THERAPEUTIC RESISTANCE ϭϵ STAT 3 IRS EGFR MEK Tumor Regression Erlotinib ERK PI 3 K AKT Tumor Survival Tumor Survival Buparlisib Ruxolitinib Blocking survival pathways NT 219 NT 219 STAT 3 IRS ONCOPROTEIN DRUG MEK / ERK TUMOR REGRESSION Proof of Concept: PDX model
Slide 20: NT219 + Targeted Therapies: Established Efficacy in PDX Models
20 NSCLC Exon 19 deletion EGFR and T 790 M, biopsy of bone marrow metastasis, patient previously progressed on afatinib and osimertinib NT 219 + TARGETED THERAPIES ESTABLISHED EFFICACY IN PDX MODELS R/M HNSCC metastasis, patient previously progressed on chemoradiation, several chemotherapies, and pe
Slide 21: NT219 + anti-PD1 Re-sensitizes Refractory Tumors
21 NT 219 + α - PD 1 RE - SENSITIZES TO REFRACTORY α - PD 1 TUMORS 21 * Double autologous model - Tumors & PBMCs are from the same patient (#RA 236 ) | Keytruda - 6 mg/kg IP, NT 219 - 60 mg/kg IV PDX model Humanized PDX of Esophagus Cancer (refractory to pembrolizumab) Drug Pembrolizumab (Keytruda ®
Slide 22: First Market Opportunity: Recurrent or Metastatic SCCHN
22 FIRST MARKET OPPORTUNITY | RECURRENT OR METASTATIC SQUAMOUS CELL CARCINOMA OF HEAD AND NECK (SCCHN) EGFR and PD(L) - 1 are the only clinically validated targets in SCCHN Cetuximab inhibits EGFR signaling and promotes ADCC in EGFR expressing tumors STAT 3 and IRS - to - AKT activation contributes
Slide 23: NT219 Monotherapy and Combination Phase 1/2 Study Design
23 NT 219 MONOTHERAPY AND COMBINATION PHASE 1 / 2 STUDY DESIGN 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 NT 219 , alone in adults with recurrent or metastatic solid tumors and in c
Slide 24: Advancing clinical-stage novel oncology therapies
24 Advancing clinical - stage novel oncology therapies x CM 24 - First - in - class α - CEACAM 1 mAb , clinical collaboration with x NT 219 - First - in - class, small molecule, dual inhibitor of IRS 1 / 2 and STAT 3 x H 2:21 - Two phase 1 study readouts x Strong balance sheet and cash position Mark
Slide 25: Committed to providing cancer patients first-in-class therapies
25 We are committed to providing cancer patients with first - in - class therapies to OVERCOME tumor drug resistance, ENHANCE treatment response and SLOW tumor progression
Slide 26: Appendix A - CM24
26 Appendix A - CM 24
Slide 27: Inhibition of Melanoma Growth Following CM24 and CM24 + TIL
27 INHIBITION OF MELANOMA GROWTH FOLLOWING CM 24 AND CM 24 + TIL TREATMENT CM 24 ACTIVITY IS DEMONSTRATED AS SINGLE AGENT AND IN COMBINATION WITH TILS * P< 0.05 TGI 71 % * P< 0.05 TGI 45 % 27
Slide 28: Phase 1 PK Data: Saturation Not Reached up to 10 mg/kg
28 PHASE 1 PK DATA SATURATION WAS NOT REACHED WITH DOSES UP TO 10 MG/KG Slower clearance with increasing dose Higher half - life with increasing dose 0.1 mg/ kg 0.3 mg/ kg 1 mg/ kg 3 mg/ kg 10 mg/ kg
Slide 29: Appendix B - NT219
29 Appendix B - NT 219
Slide 30: Selected Publications
30 SELECTED PUBLICATIONS Menashe Bar - Eli Michael Karin Michael Cox Alexander Levitzki
Slide 31: NT219 Suppresses β-Catenin Activity in CRC Cells
31 Prof. Ido Wolf, Head of Oncology Division, Tel Aviv Sourasky Medical Center The colon cancer SW 403 cells, where IRS 2 is overexpressed, demonstrate enhanced b - catenin activity, IRS 1 / 2 inhibitor NT 219 , as well as the PI 3 K inhibitor Alpelisib , suppress the increased b - catenin activity
Slide 32: NT219 Pancreatic Cancer in Combination with Gemcitabine
32 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® ) NT 219 | PANCREATIC CANCER IN COMBINATION WITH GEMCITABINE 32
Slide 33: RNA Sequencing Analysis of Tumors Following Treatment
33 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® ) RNA SEQUENCING | ANALYSIS OF TUMORS FOLLOWING TREATMENT
Slide 34: Appendix C - CONSENSI
34 Appendix C - CONSENSI®
Slide 35: CONSENSI: From IND to the U.S. Market
35 CONSENSI® | FROM IND TO THE U.S. MARKET CONSENSI ® is the only NSAID whose labeling indicates reduction of blood pressure and consequent risk reduction of heart attack, stroke and death Full U.S. Prescribing Information is available at http://www.consensi.com Celecoxib , a COX - 2 selective NSAID
Slide 36: CONSENSI Phase III Trial Results
36 CONSENSI ® PHASE III TRIAL RESULTS Primary efficacy endpoint was successfully achieved (P= 0.001 ) Demonstrated 2.5 x better blood pressure reduction than FDA requirement ( 50 % of amlodipine arm) Demonstrated consistent reduction in all measures of blood pressure Observed beneficial renal functi
Slide 37: Kitov Commercial Drug: CONSENSI
37 KITOV COMMERCIAL DRUG: CONSENSI® Approved for marketing by U.S. FDA on May 31 , 2018 Clinical data showed Consensi Ρ was more effective at lowering blood pressure than amlodipine alone Clinical data also demonstrated beneficial renal function measures Formulated with 200 mg celecoxib and three di
Slide 38: CONSENSI U.S. Target Markets
38 CONSENSI ® U.S. TARGET MARKETS CONSENSI® targets osteoarthritis (OA) patients currently treated with NSAIDs (celecoxib as well as others) who also suffer from existing or newly diagnosed hypertension OSTEOARTHRITIS 50 million patients* NSAIDs 60 % of all OA Rxs * Arthritis Foundation: http://www.
Slide 39: Thank You
39 Thank You