Purple Biotech Ltd. · TASE:PPBT
Purple Biotech — Kitov Pharma — Investor Presentation (October 2019)
45 slides from Purple Biotech's investor presentation, Oct 18, 2019
Slide 1: Corporate Presentation October 2019
Thank you Corporate Presentation October 2019
Slide 2: Forward-Looking Statements and Safe Harbor
Forward - Looking Statements and Safe Harbor 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 Private Securiti
Slide 3: Kitov Pharma: clinical-stage company advancing first-in-class oncology therapies
Kitov Pharma CM - 24 – Inhibitor of CEACAM1 NT - 219 – Dual inhibitor of IRS 1/2 and STAT3 • NASDAQ/TASE:KTOV – 33 % of shares held by healthcare focused investors* including Orbimed Advisors, Pontifax – Market Cap: $ 22 M* ($ 0.74 /ADS) – 6 - month average trading volume: 265 K shares • $ 8 M Cash
Slide 4: Experienced Leadership
Experienced Leadership Eric K. Rowinsky , MD Chairman of the Board Formerly CMO at ImClone , Stemline , Board member at Biogen Inc. Isaac Israel Chief Executive Officer Formerly CEO of BeeContact Ltd. (TASE:BCNT), NextGen Biomed (TASE: NXGN) Bertrand Liang, MD, PhD, MBA, AMP Medical Director Oncolog
Slide 5: From Development to Commercialization
Program Indication Preclinical Phase 1 Phase 2 Phase 3 Partners Value Drivers CM - 24 Non - Small Cell Lung Cancer (combination with nivolumab ) (Clinical Collaboration) Study initiation H2:20 Phase 1 data H1:21 NT - 219 Head and Neck Cancer (combination with cetuximab) Study initiation Q 1:20 Pha
Slide 6: CM-24 – Inhibitor of CEACAM1
Advancing first - in - class Oncology Therapies CM - 24 – Inhibitor of CEACAM 1 6
Slide 7: CM-24 Immune Checkpoint Inhibitor
CM - 24 I mmune checkpoint inhibitor 7 Targets a Novel Immune Checkpoint ▪ First - in - class mAb blocking CEACAM 1 ▪ Conceptually analogous to anti - PD(L) 1 Well Tolerated in a Clinical Trial ▪ Studied as a monotherapy in a phase 1 ▪ Doses up to 10 mg/kg Demonstrated Efficacy in Preclinical Models
Slide 8: CEACAM1 Plays a Pivotal Role in the Immune System
• CEACAM 1 (Carcinoembryonic Antigen Cell Adhesion Molecule 1 ) - member of the Human CEA Family • Conceptually, analogous to PD - 1 /PDL - 1 • Interacts with both CEACAM 1 and CEACAM 5 • Regulates TIM - 3 - mediated tolerance and exhaustion * • High expression in tumor and in tumor - infiltrating i
Slide 9: CEACAM1 and TIM-3
Huang et al, CEACAM 1 regulates TIM - 3 - mediated tolerance and exhaustion; Nature, 2015 DOI: https://doi.org/ 10.1038 /nature 13848 CEACAM - 1 + TIM 3 combination introduces an innovative approach to TIM - 3 regulation • TIM - 3 is co - expressed and forms a heterodimer with CEACAM 1 • The presenc
Slide 10: CM-24 MOA: Blocks CEACAM1-Mediated Interactions
Markel et al, J Immunol 2002 , 2006 ; Immunology, 2008 ; Cancer Immunol Immunother 2010 ; Ortenberg et al, Mol Cancer Ther 2012 CM - 24 MOA: Blocks CEACAM 1 - mediated interactions • CM - 24 is a humanized IgG 4 mAb highly specific to the extracellular domain of CEACAM 1 with Nano - molar affinit
Slide 11: Anti-Cancer Effect Following Treatment with CM-24 + TIL and Anti-PD1
• Xenograft, lung lesion, Mel 526 (IV) • Tumor burden was monitored 26 days post last CM - 24 treatment TIL + IgG TIL + CM - 24 Naive Combination index ( CI) = 0.15 < 1 synergism Anti - Cancer Effect Following Treatment with CM - 24 + TIL and CM - 24 + Anti - PD 1 Significant benefits as both s
Slide 12: CM-24 Phase 1 Monotherapy Trial
CM - 24 Phase 1 Monotherapy Trial • Open - label, multi - dose escalation study to assess safety and tolerability of CM - 24 • Conducted by Merck in 4 centers US: UCLA, Yale; Israel: Sheba, Sourasky • Heavily pre - treated patients with a median of 3 prior regimens (range 2 - 7 ) and a median of 4 p
Slide 13: Merck Concluded that Saturation Likely Requires >10 mg/kg
Merck Concluded that Saturation Likely Requires > 10 mg/kg Merck models 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 3 W, 10 mg/kg is
Slide 14: Market opportunity: Non-Small Cell Lung Cancer
Market opportunity: Non - Small Cell Lung Cancer • Preclinical data supports significant synergistic benefit • Receptor saturation with CM - 24 is better achieved with a Q 2 W regimen and is aligned with the Opdivo protocol • Collaboration with Bristol - Myers Squibb, a leader in immuno - Oncolog
Slide 15: CM-24 Accelerated Biomarker-driven Clinical Development
CM - 24 Accelerated Biomarker - driven Clinical Development Non Small Cell Lung Cancer (NSCLC) patients Phase 1 Dose escalation N <= 15 CM - 24 + nivolumab 15 Phase 2 Expansion cohort CEACAM 1 + CM - 24 + nivolumab Accelerated approval strategy if compelling clinical benefit data Pivotal study or 1
Slide 16: NT-219 – Dual inhibitor of IRS1/2 and STAT3
Advancing first - in - class oncology therapies NT 219 – Dual inhibitor of IRS 1 / 2 and STAT 3 16
Slide 17: NT-219 Drug Resistance Prevention
NT - 219 Drug Resistance Prevention 17 Unique MoA ▪ Inhibits two key resistance signaling proteins: IRS 1 / 2 and STAT 3 Enhances Every Treatment Regimen ▪ In combination with immuno - oncology, targeted and chemo therapies Efficacious in Multiple PDX Models ▪ Prevents, delay and reverses resistance
Slide 18: IRS1/IRS2 and STAT3 Role in Cancer Drug Resistance
IRS 1 / 2 IRS 1 / 2 and STAT 3 Role in Cancer Drug Resistance STAT 3 • Part of the IGFR complex • Phosphorylated on tyrosine residues and triggers activation of PI 3 K/AKT and MEK/ERK signaling pathways • Regulates cell proliferation, protein synthesis, survival, gene expression and apoptosis • A
Slide 19: NT-219 MOA: Inhibition of Both STAT3 and IRS
NT - 219 MOA: Inhibition of Both STAT 3 and IRS is R equired to Overcome Resistance 19 STAT 3 IRS EGFR MEK Tumor Regression Erlotinib ERK PI 3 K AKT Tumor Survival Tumor Survival Buparlisib Ruxolitinib Overcoming drug resistance NT 219 NT 219 STAT 3 IRS ONCOPROTEIN DRUG MEK / ERK TUMOR REGRESSION By
Slide 20: Efficacy Demonstrated in Combination with Multiple Drug Classes
Efficacy Demonstrated in Combination with Multiple Drug Classes in Preclinical Models Increased efficacy Expanded target population Extended treatment duration Head & Neck Colon ( wt KRAS) Lung Melanoma Thyroid Uterine Pancreatic Esophagus Prostate Targeted Drugs Chemotherapy Immunotherapy 20
Slide 21: NT-219 Prevents Acquired Resistance to Erlotinib
NT 219 Prevents Acquired Resistance to Erlotinib 21 PDX model Head & Neck Cancer Drugs Erlotinib ( Tarceva ®) Vehicle (n= 8 ) Erlotinib (n= 8 ) NT 219 (n= 8 ) 0 200 400 600 800 1,000 1,200 1,400 1,600 0 2 4 6 8 10 12 14 16 18 Tumor Volume (cm 3 ) 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 Erlotinib Response
Slide 22: NT-219 Reverses Erlotinib-acquired Resistance
NT 219 Reverses Erlotinib - acquired Resistance 22 PDX model Head & Neck Cancer Drugs Erlotinib ( Tarceva ®) 2.5 2.0 1.5 1.0 0.5 0 Erlotinib Response Acquired resistance Treatment initiated after resistance has been acquired Days NT 219 + Erlotinib
Slide 23: NT-219 Delays Tumor Recurrence
NT 219 Delays Tumor Recurrence PDX model Head & Neck Cancer Drug Cetuximab (Erbitux®) Treatment period 9 days Days 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 NT 219 (n= 3 ) Vehicle (n= 3 ) Cetuximab (n= 4 ) NT 219 + Cetuximab (n= 4 ) 23
Slide 24: Market Opportunity: Recurrent or Metastatic SCCHN
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 • STAT 3 and IRS - to - AKT activation contributes to resistance to cetuximab
Slide 25: 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 25 Phase 2 Expansion cohort N = 30 NT - 219 + cetuximab Accelerated approval strategy if compelling clinical benefit data Pivotal study NT - 219 + cetuximab v
Slide 26: Kitov Commercial Drug: Consensi
Kitov Commercial Drug: 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 th
Slide 27: 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
Slide 28: Consensi commercialization partners
Consensi ™ commercialization partners South Korea - Exclusively licensed to Kuhnil Pharmaceuticals (March 2017 ) U.S. - Exclusively licensed to Coeptis Pharmaceuticals. Milestone payments up to $ 99.5 M, 20 % royalties (January 2019 ) China - Exclusively licensed to Changshan Pharma. Milestone pa
Slide 29: Milestones
Milestones Q 4 2019 Q 4 2019 Q 4 2019 Q 1 2020 Q 1 2020 Q 1 2020 H 1 2020 H 2 2020 CM - 24 Transaction closing NT - 219 IND clarance NT - 219 Initiation of phase 1 / 2 clinical study NT - 219 Collaboration agreement with potential strategic partner Consensi ™ complete manufacturing and prepare fo
Slide 30: Attractive opportunity
Attractive opportunity A clinical - stage company advancing first - in - class oncology therapies x Two clinical stage assets targeting significant unmet needs x Strong partners and collaborators x Commercial stage drug to provide additional cash flow x Institutional healthcare focused investors x C
Slide 31: Thank you
Thank you We are committed to providing 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 32: Appendix A - CM-24
Appendix A - CM 24
Slide 33: 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 34: Phase 1 PK Data
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 35: Appendix B - NT-219
Appendix B - NT 219
Slide 36: NT-219 Re-sensitizes Tumors to Anti-PD1
NT 219 Re - sensitizes Tumors to Anti - PD 1 36 * 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 37: NT-219 Overcomes Resistance to Gemcitabine in Pancreatic Cancer PDX Models
NT 219 Overcomes Resistance to Gemcitabine in Pancreatic Cancer PDX Models 37 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 38: RNAseq Analysis of Tumors Following Treatment
RNAseq Analysis of Tumors Following Treatment C onfirming NT - 219 Mechanism of Action 38 PDX model Pancreatic Cancer Drug Gemcitabine ( Gemzar ® )
Slide 39: Selected Publications
Selected Publications 39 Menashe Bar - Eli Michael Karin Michael Cox Alexander Levitzki
Slide 40: Appendix C - Consensi Clinical Data
Appendix C - Consensi ™ Clinical Data
Slide 41: 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
Slide 42: 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 Anal
Slide 43: 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 f
Slide 44: 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 pr
Slide 45: 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.