Enlivex Ltd. · NASDAQ:ENLV
Enlivex — Enlivex Therapeutics — Investor Presentation (February 2021)
36 slides from Enlivex's investor presentation, February 2021
Slide 1: Beyond CD47, SIRPα, IL-6 & TNF-α
Ticker: ENLV Beyond CD47, SIRP⍺, IL-6 & TNF-⍺ Off-the-shelf, universal, macrophage reprogramming cell therapies for life-threatening diseases February 2021
Slide 2: Forward-Looking Statements
Forward-Looking Statements These slides and the accompanying oral presentation contain forward-looking statements and information. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels or activi
Slide 3: Macrophage reprogramming
Macrophage reprogramming Paradigm shift – homeostasis instead of “anti-inflammatory (M2)” or “”pro- inflammatory (M1)”
Slide 4: Macrophages are tissue-resident immune cells critical for innate immunity
Macrophages are tissue-resident or infiltrated immune cells critical for innate immunity • Macrophages’ function is a sum of their designation, the local environment in which they reside, and the type of situation or pathogen to which they are exposed VIEW S E R I E S :outRofEtheir • Reprogrammed P
Slide 5: Macrophage homeostasis implies proper function for its specific tissue, environment and challenge
Macrophage homeostasis implies proper function for its specific tissue, environment and challenge Reprogramming imbalanced macrophage populations can lead to disease resolution Sepsis, COVID-19 ARDS, ARF post heart surgery Macrophage Homeostasis Pro-homeostasis Pro-inflammatory Pro-organ restoration
Slide 6: Solid cancer: kill or reprogram non-homeostatic, pro-tumor macrophages (TAMs) in the TME
Solid cancer: kill or reprogram non-homeostatic, pro-tumor macrophages (TAMs) in the tumor microenvironment (TME) Multiple axes for homeostatic macrophage functionality multiple strategies to kill or reprogram non-homeostatic, pro- within the tumor microenvironment (TME), tumor macrophages (TAMs) Re
Slide 7: Sepsis: negative macrophage reprogramming, no homeostasis
Sepsis: negative macrophage reprogramming, no homeostasis Source: EMBO Molecular Medicine 12:e10128 | 2020 2020 Corporate Presentation I 7
Slide 8: Allocetra Mechanism of Action
AllocetraTM Mechanism of Action Restoring immune homeostasis through reprogramming of macrophages
Slide 9: Allocetra for macrophage reprogramming
Allocetra™ for macrophage reprogramming Proprietary, universal, off-the-shelf, macrophage-reprogramming cells AllocetraTM characteristics AllocetraTM delivery into macrophages via engulfment AllocetraTM cell q Mononuclear cells collected from healthy donors q Modified through a proprietary process t
Slide 10: Allocetra for macrophage reprogramming: pipeline of indications
Allocetra™ for macrophage reprogramming Pipeline of reprogrammable macrophage-modulated indications Global EU Conditional Post EU Marketing Indication Pre-Clinical Phase Ib Phase IIb Market Size Marketing Approval US Phase 3 Phase IIb Initiation Organ failure associated with Sepsis $33B Completed Q1
Slide 11: Allocetra: Reprogramming macrophages responsible for organ failure in sepsis and COVID-19
AllocetraTM Reprogramming macrophages responsible for organ failure in sepsis and COVID-19
Slide 12: Sepsis is the 3rd leading cause of death in the U.S. – $33B target market
Sepsis is the 3rd leading cause of death in the U.S. – $33B target market* There are currently no FDA approved drugs for the treatment of sepsis SEPSIS CATEGORIES Each year, at least 1.7 million adults in America develop sepsis. Nearly 270,000 Americans die as a result of sepsis each year. Organ Mil
Slide 13: Cytokine/Chemokine network in sepsis
Cytokine/Chemokine network in sepsis: the impossible task of resolving sepsis with inhibition of a certain cytokine or signaling pathway Ghrelin G-CSF MΦ: Macrophages GM-CSF Activation TREM-1 Inhibition sTNFR1 Chemotaxis Gro-α/β MCP-1 Bacterial Downregulated in most of the patients TNFα infection Do
Slide 14: Allocetra Phase Ib clinical trial of macrophage reprogramming in sepsis patients
AllocetraTM Phase Ib clinical trial of macrophage reprogramming In sepsis patients
Slide 15: Reprogrammed macrophages in sepsis patients return to homeostatic state (1)
Reprogrammed macrophages in sepsis patients return to homeostatic state (1) Phase Ib clinical trial data, change from screening, pro-inflammatory cytokines A B C 5000 3000 IL-6 IL-6 150 100 TNF-⍺ TNF-a 20 15 IL-1-β IL-1b 10 1000 50 5 900 50 5 700 40 pg/ml 4 pg/ml pg/ml 500 300 30 3 100 20 2 100 50 1
Slide 16: Reprogrammed macrophages in sepsis patients return to homeostatic state (2)
Reprogrammed macrophages in sepsis patients return to homeostatic state (2) Phase Ib clinical trial data, change from screening, anti-inflammatory cytokines E 50 IL-10 IL-10 5000 F 40000 IL-1R⍺ IL-1Ra IL-6 G 1000 G-CSF Normal values 30 3000 20000 800 600 G-CSF 10 10 10000 300 Patient 001 Patient 008
Slide 17: Sequential Organ Failure Assessment (SOFA) Score
Sequential Organ Failure Assessment (SOFA) Score The sequential organ failure assessment score (SOFA score), previously known as the sepsis- related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person'
Slide 18: High degree of matching: treated vs controls
High degree of matching: treated vs controls Treated (n=10) Matched Controls (n=37) Average age 71.5 (51-83) 71.25 (50-83) Male/female 80/20 80/20 Average diagnosis SOFA 3.4 (2-6) 3.47 (2-7) Average diagnosis Apache II score 12.3 (8-21) 14.25 (5-24) Sepsis source Pneumonia 50% 53% Biliary infections
Slide 19: Allocetra macrophage reprogramming leads to improved outcomes for sepsis patients
Allocetra macrophage reprogramming leads to improved outcomes for sepsis patients TM # Total Controls 37 Maximal change in SOFA score, diagnosis to day 28 patients Treated 10 Day 28 # % Died Controls 10 27% -- p<0.0001 T-test Treated 0 0 -- Alive Day 28 SOFA Day 28 alive Avg. Recovery delta vs pre-
Slide 20: Statistically significant improvement in hospitalization and SOFA vs. matched controls
Allocetra macrophage reprogramming leads to improved outcomes for sepsis patients TM Statistically significant improvement in hospitalization and SOFA vs. matched controls Time to ICU discharge Average SOFA score during 28 days 100 Drastic difference in organ failure resolution Proportion of hospita
Slide 21: Clinical summary of macrophage reprogramming in sepsis Phase Ib
Clinical summary of macrophage reprogramming in sepsis Phase Ib: complete recovery from any organ failure for all 10 patients and 100% 28-day survival Sepsis clinical characteristics and organ recovery Organ Dysfunction Each patient had at least 2 organ dysfunctions, maximum of 5 Kidney 3/9 patients
Slide 22: Sepsis – Allocetra Phase IIb clinical plan
Sepsis – AllocetraTM macrophage reprogramming Phase IIb clinical plan Sepsis Phase IIb Addressable global market $33 Billion market (severe Sepsis only) Type Controlled, randomized, multi-center (10 centers) Patients 120-160, SOFA < 10, Pneumonia-sourced Duration 28 days / patient Recruitment 12 Mon
Slide 23: Allocetra Phase Ib & II Clinical Trials in COVID-19 Patients
AllocetraTM Phase Ib & II Clinical Trials in COVID-19 Patients in Severe or Critical Condition
Slide 24: Allocetra: positive Phase Ib and interim Phase II results in COVID-19
AllocetraTM: positive Phase Ib and interim Phase II results in COVID-19 o 0/21 (0%) mortality on day-28 o Average duration of hospitalization post administration of AllocetraTM for discharged patients was 5.6 days o 19/21 (90.5%) patients recovered and were discharged from the o 2/21 (9.5%) patients
Slide 25: Allocetra Macrophage reprogramming in solid tumor microenvironment
AllocetraTM Macrophage reprogramming in solid tumor microenvironment Unique & differentiated value proposition
Slide 26: The TME is loaded with pro-tumor macrophages (TAMs)
The TME is loaded with pro-tumor macrophages (TAMs), which are macrophages reprogrammed by the tumor and have a drastically different gene expression D D Gene expression varies drastically in TAMs vs anti-cancer macrophages* TAMs are macrophages that Tumor to Non-Tumor Relative Expression Lung Macro
Slide 27: Allocetra: novel reprogramming of pro-tumor macrophages
AllocetraTM: novel reprogramming of pro-tumor macrophages Key company universe Novartis, 47, Trillium Infinity, Arcus Celgene Celldex Enlivex BMS, Amgen ALX, Celgene MedImmune Nektar, GSK AbbVie Macrophage properties Syndax Surface Corvus, Pfizer MedImmune Reprogramming Inhibit or trigger Inhibit or
Slide 28: Preclinical data
AllocetraTM Macrophage reprogramming in solid tumor microenvironment Preclinical data
Slide 29: Allocetra: reprogramming of peritoneal pro-tumor macrophages
AllocetraTM: reprogramming of peritoneal pro-tumor macrophages Preclinical study model: solid tumor engineered to express CD19, making it potentially responsive to CD19 CAR-T Macrophage reprogramming effect measured via single cell analysis SCID Survival/Histology Days: 1 6 12 18 24 30 40 Human Hela
Slide 30: Allocetra: reprogramming of peritoneal pro-tumor macrophages
AllocetraTM: reprogramming of peritoneal pro-tumor macrophages A B C D 2020 Corporate Presentation I 30
Slide 31: Allocetra macrophage reprogramming synergistic with CD19 CAR-T
Allocetra macrophage reprogramming synergistic with CD19 CAR-T D89* Allocetra (opsonized, not engulfed by macrophages) has no programming nor clinical effect 120 HeLaCD19 HeLa-CD19 + CAR-T 100 HeLa-CD19 + CAR-T + Allocetra-OTS 80 HeLa-CD19 + CAR-T + % Survival D89E_Allocetra-OTS 60 Complete remissio
Slide 32: Planned/executed milestones
Planned/executed milestones Q1 2021 Q2 2021 Q3 2021 Q1 2022 Top-line data from Emergency-use Interim data Initiation of macrophage macrophage designation for macrophage reprogramming PD-1 reprogramming COVID-19 reprogramming combination COVID-19 Phase II Severe/critical sepsis Phase IIb undisclosed
Slide 33: Financial Summary
Financial Summary NASDAQ GS ENLV Cash $36MM (Sep 30, 20201) Debt None Shares 14.3MM Outstanding Funded Q1-2023 Through 1 Cash balance as reported for Sep 30 2020 plus Q4 warrant exercises 33
Slide 34: Management
Management Shai Novik Founder of Prolor Biotech, Sold in 2013 ($560mm transaction). Lead product partnered to Pfizer, $295 Executive Chairman million down payment, $275 upon FDA approval. Phase III endpoint met Oct 2019. Oren Hershkovitz Former Director of CMC, VP R&D and CEO of OPKO Biologics (PROL
Slide 35: Board Of Directors
Board Of Directors Shai Novik Founder of Prolor Biotech, Sold in 2013 Brian Schwartz, M.D. Former CMO of Arqule through its $2.7 billion Executive Chairman ($560mm transaction). Lead product Director acquisition by Merck in 2020. Previously, partnered to Pfizer, $295 million down responsible for the
Slide 36: Thank You
Ticker: ENLV Thank You www.enlivex.com February 2021
Enlivex Therapeutics — Investor Presentation (February 2021) on 6ix