Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Kitov Pharma — Investor Presentation (September 2019)
46 slides from Purple Biotech's investor presentation, Sep 10, 2019
Slide 1: Corporate Presentation September 2019
Thank you Corporate Presentation September 2019
Slide 2: Forward-Looking Statements and Kitov's Safe Harbor Statement
Forward - Looking Statements and Kitov' s Safe Harbor Statement This presentation is not a prospectus or offer of securities for subscription or sale in any jurisdiction . Certain statements in this presentation are forward - looking statements within the meaning of the safe harbor provisions of the
Slide 3: About Kitov
About Kitov • Publicly traded on TASE 2013 ; IPO on NASDAQ in November 2015 • Tickers: KTOV (ADSs); KTOVW (Warrants) • Cash on hand (as of June 30 , 2019 ): Ε $ 8 M + $ 3.5 M of investment pending closing of CM - 24 transaction • Market Cap: ~$ 27 M* • ~ 35 % of the shares held by blue - chip, insti
Slide 4: Commercial and Development Pipeline
Program Indication Preclinical Phase 1 Phase 2 Phase 3 Market Partners Consensi™ Osteoarthritis Pain and Hypertension Commercial partners: Coeptis Pharmaceuticals - U.S. CSBio - China Kuhnil Pharmaceuticals - S. Korea CM - 24 Non - Small Cell Lung Cancer (combination with nivolumab) Bristol - Myers
Slide 5: CM-24
CM - 24
Slide 6: About CM-24
About CM - 24 6 Targets a Novel Immune Checkpoint CM - 24 is a first - in - class mAb blocking CEACAM1, a novel immune checkpoint inhibitor, conceptually analogous to PD1 - PDL1 Well Tolerated in a Phase 1 Study CM - 24 was well tolerated as a monotherapy in a Phase 1 study in doses up to 10 mg/kg D
Slide 7: CEACAM is a Member of the Human CEA Family
CEACAM 1 is a Member of the Human CEA Family ( Carcinoembryonic Antigen Cell Adhesion Molecule) Gray - Owen and Blumberg, CEACAM1: contact - dependent control of immunity, Nature Review Immunology , 2006, DOI: https://doi.org/10.1038/nri1864 • Known to interact with both CEACAM1 and CEACAM5 • Also k
Slide 8: CEACAM Expression in Tumor and Tumor-Infiltrating Immune Cells
CEACAM 1 Expression in Tumor and in Tumor - Infiltrating Immune Cells CEACAM 1 staining with MGR 1 (murine version of CM - 24 ) on various tissue microarrays from different cancer types % CEACAM 1 staining in tumor CEACAM 1 + Immune cells Bladder carcinoma Colon Pancreas Melanoma ( 70 %) Bladder ( 9
Slide 9: CM-24 Mechanism of Action
CM - 24 - Mechanism of Action (Tumor) CEACAM 1 / 5 – (T - cell) CEACAM 1 interaction prevents killing of tumor cells through : a) inhibition of the immune activity of TILs b) lowering phosphorylation of immuno - receptors, and c) reduction of the phosphorylation level of ZAP 70 in T cells Markel et
Slide 10: Sustained Inhibition of Lung Tumor Growth Following Treatment with CM-24 + TIL
Sustained Inhibition of Lung Tumor Growth Following Treatment with CM - 24 + TIL Tumor weight reduction Reduction of number of lung lesions • Xenograft, lung lesion melanoma model • Tumor burden was monitored 26 days post last CM - 24 treatment TIL + IgG TIL + CM - 24 Naive Average tumor weight ( mg
Slide 11: Synergistic Anti-Cancer Effect Following Treatment with CM-24 + Anti-PD1
Synergistic Anti - Cancer Effect Following Treatment with CM - 24 + Anti - PD 1 Combination index ( CI) = 0.15 < 1 synergism
Slide 12: Phase 1 CM-24 Trial Data
Phase 1 CM - 24 Trial Data • Open - label, multi - dose escalation study to assess the safety and tolerability of CM - 24 as a monotherapy and in combination with pembrolizumab ( Keytruda ®)* • Conducted by Merck in 4 centers (US: UCLA, Yale; Israel: Sheba, Ichilov ) • No DLTs up to 10 mg/kg • Drug
Slide 13: Phase 1 PK Data
Phase 1 PK Data Saturation was not reached with doses up to 10 mg/kg Merck’s conclusion: Saturation likely requires > 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 14: Phase 1 PK Data - TMDD Model
Phase 1 PK Data 2 - compartment PK model including TMDD was performed by Merck. Model was simulated to characterize TMDD saturation: Simulated TMDD saturation at Ctrough with Q 2 W regimen Predictions with Q 3 W regimen ( not clinically tested) • Keytruda®’s administration regimen is Q 3 W • With Q
Slide 15: CM-24 Clinical Development Plan
CM - 24 Clinical Development Plan Non Small Cell Lung Cancer (NSCLC) patients Phase 1 Dose escalation N <= 15 CM - 24 + nivolumab 15 Phase 2 Expansion cohort N = 30 CM - 24 + nivolumab Accelerated approval strategy if compelling clinical benefit data Pivotal study or • In Collaboration with Bristol
Slide 16: NT-219
NT - 219
Slide 17: About NT-219
About NT - 219 17 Unique MoA NT - 219 is an inhibitor of two signaling proteins involved in drug resistance: Insulin Receptor Substrate 1 and 2 (IRS 1 / 2 ) and Signal Transducer and Activator of Transcription 3 (STAT 3 ) Enhances Every Treatment Regimen Efficacy in PDX models was demonstrated in co
Slide 18: IRS1/2 and STAT3 Key Signal Transducers in Drug Resistance
Adapted from Clinics vol. 73 supl. 1 2018 IRS 1 / 2 : IRS 1 / 2 and STAT 3 Key Signal Transducers Activated as a Feedback Response to Anti - Cancer Drugs, Leading to Drug Resistance STAT 3 : • Part of the IGFR complex • Phosphorylated on tyrosine residues and triggers activation of PI 3 K/AKT and ME
Slide 19: NT-219 Mechanism of Action
NT 219 - Mechanism of Action 19 TUMOR REGRESSION Initial Response Drug resistance Overcoming drug resistance NT 219 NT 219 Feedback STAT 3 TUMOR PROGRESSION IRS TUMOR PROGRESSION AKT Feedback ONCOPROTEIN DRUG MEK / ERK STAT 3 IRS ONCOPROTEIN DRUG MEK / ERK TUMOR REGRESSION DRUG ONCOPROTEIN MEK / ERK
Slide 20: Inhibition of Both STAT3 and IRS/PI3K is Required to Overcome Resistance
Inhibition of Both STAT 3 and IRS/PI 3 K is Required to Overcome Resistance 20 PDX of H&N cancer STAT 3 IRS EGFR MEK Tumor Regression Erlotinib ERK PI 3 K AKT Tumor Survival Tumor Survival Drug - resistance Buparlisib Ruxolitinib
Slide 21: Efficacy Demonstrated in Combination with Multiple Drug Classes in Preclinical Models
Efficacy Demonstrated in Combination with Multiple Drug Classes in Preclinical Models Expected outcomes are: Increased efficacy Expanded target population Extended treatment duration Head & Neck Colon ( wt KRAS) Lung Melanoma Thyroid Uterine Pancreatic Esophagus Prostate Targeted Drugs Chemotherapy
Slide 22: NT-219 Prevents Acquired Resistance to Erlotinib
22 NT 219 Prevents Acquired Resistance to erlotinib PDX model Head & neck cancer Drugs Erlotinib (Tarceva®)
Slide 23: NT-219 Reverses Erlotinib-Acquired Resistance
23 NT 219 Reverses erlotinib - acquired Resistance PDX model Head & neck cancer Drugs Erlotinib (Tarceva®)
Slide 24: NT-219 Delays Tumor Recurrence
24 NT 219 Delays Tumor Recurrence PDX model Head & neck cancer Drug Cetuximab (Erbitux®)
Slide 25: Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN) • EGFR and PD(L) - 1 are the only clinically validated targets in SCCHN • Cetuximab inhibits EGFR signaling and promotes ADCC • STAT 3 and IRS - to - AKT activation contributes to resistance to cetuximab in HNSCC * G
Slide 26: NT-219 Clinical Development Plan
NT - 219 Clinical Development Plan Recurrent or metastatic SCCHN patients Phase 1 Dose escalation N <= 24 4 - week cycle NT - 219 + cetuximab 26 Phase 2 Expansion cohort N = 30 NT - 219 + cetuximab Accelerated approval strategy if compelling clinical benefit data Pivotal study NT - 219 + cetuximab v
Slide 27: Consensi
Consensi™ “wwe 27
Slide 28: About Consensi
About Consensi™ • Approved for marketing by U.S. FDA on May 31 , 2018 • Clinical data showed Consensi™ 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 different dosag
Slide 29: Consensi U.S. Target Markets
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.arth
Slide 30: Consensi Commercialization Partners
Consensi™ Commercialization Partners South Korea - Exclusively licensed to Kuhnil Pharmaceuticals (March 2017 ) U.S. - Exclusively licensed to Coeptis Pharmaceuticals. Milestone payments $ 3.5 M, 60 % - 40 % profit sharing (January 2019 ) China - Exclusively licensed to Changshan Pharma. Milestone p
Slide 31: Upcoming Milestones
Upcoming Milestones Expected Date Milestone Q 3:19 CM - 24 - Closing of the transaction Q 4:19 NT - 219 - IND submission to FDA Q 1:20 NT - 219 - Initiation of a phase 1/2 clinical study H 2:19 NT - 219 - Collaboration agreement with potential strategic partner H 2:19 Consensi™ - Complete manufactur
Slide 32: About Kitov
About Kitov • Publicly traded on TASE 2013 ; IPO on NASDAQ in November 2015 • Tickers: KTOV (ADSs); KTOVW (Warrants) • Cash on hand (as of June 30 , 2019 ): Ε $ 8 M + $ 3.5 M of investment pending closing of CM - 24 transaction • Market Cap: ~$ 27 M* • ~ 35 % of the shares held by blue - chip, insti
Slide 33: Thank you
Thank you Our mission is to provide cancer patients with first - in - class therapies to overcome tumor drug resistance, enhance treatment response and slow tumor progression Contact us: Email: IR@kitovpharma.com www.kitovpharma.com
Slide 34: Appendix A - CM-24
Appendix A - CM 24
Slide 35: Inhibition of Melanoma Growth Following CM-24 and CM-24 + TIL Treatment
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 % 35
Slide 36: Appendix B - NT-219
Appendix B - NT 219
Slide 37: NT-219 Re-sensitizes Tumors to Anti-PD1
NT 219 Re - sensitizes Tumors to Anti - PD 1 37 * 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 Drug Pembrolizumab (Keytruda ® )
Slide 38: NT-219 Overcomes Resistance to Gemcitabine in Pancreatic Cancer PDX Models
NT 219 Overcomes Resistance to Gemcitabine in Pancreatic Cancer PDX Models 38 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® ) Additional newly released data for NT - 219 in reversing Pancreatic Cancer drug resistance is available on AACR PanCan poster: http://kitovpharma.investorroom.com/i
Slide 39: RNAseq Analysis of Tumors Following Treatment Confirming NT-219 Mechanism of Action
RNAseq Analysis of Tumors Following Treatment C onfirming NT - 219 Mechanism of Action 39 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® )
Slide 40: Selected Publications
Selected Publications 40 Menashe Bar - Eli Michael Karin Michael Cox Alexander Levitzki
Slide 41: Appendix C - Consensi Clinical Data
Appendix C - Consensi ™ Clinical Data
Slide 42: Medical Rationale
Medical Rationale Celecoxib (the active ingredient in Pfizer's Celebrex®) • The only widely prescribed selective COX - 2 NSAID approved in the U . S . (unlike non - selective NSAIDs, celecoxib carries limited gastrointestinal risks) • Since 2005 , has an FDA - mandated “ black box ” label warning of
Slide 43: Consensi Phase III Trial Design
Consensi™ Phase III Trial Desig n Demonstrate that the reduction in blood pressure in the Consensi™ arm is at least 50 % of the reduction in the amlodipine arm Measurement of pain was not required by FDA Primary endpoint Newly diagnosed hypertensive patients Data Collection and Statistical Analysis
Slide 44: Consensi Phase III Trial Results
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 fu
Slide 45: Consensi Phase III/IV Clinical Trial Design
Consensi™ Phase III/IV Clinical Trial Design Hypertensive patients (following a wash - out period) Data Collection and Statistical Analysis Double - blind, placebo - controlled, multi - center study N = 1 2 3 - arm trial 2 weeks of treatment Consensi™ Demonstrate that the reduction in blood pressure
Slide 46: Consensi Phase III/IV Clinical Trial Results
Consensi™ Phase III/IV Clinical Trial Results • Primary efficacy endpoint successfully met (p= 0.019 ), thus Phase III trial results validated • Statistically significant reduction of serum creatinine observed vs. baseline • Consensi™ enhanced the creatinine reduction by an average of 102 % vs. amlo
Kitov Pharma — Investor Presentation (September 2019) on 6ix