Enlivex Ltd. · NASDAQ:ENLV
Enlivex — Enlivex Therapeutics — Investor Presentation (August 2021)
37 slides from Enlivex's investor presentation, August 2021
Slide 1: Off-the-shelf, universal, macrophage reprogramming cell therapies
Off-the-shelf, universal, macrophage reprogramming cell therapies for life- threatening diseases NASDAQ Ticker: ENLV
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 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, Macrophage population homeostasis ARF post heart surgery Pro-homeostasis Pro-inflammatory Pro-organ
Slide 4: Allocetra Mechanism of Action
AllocetraTM Mechanism of Action Restoring immune homeostasis through reprogramming of macrophages
Slide 5: Allocetra for macrophage reprogramming
Allocetra™ for macrophage reprogramming Proprietary, universal, off-the-shelf, macrophage-reprogramming cells Allocetra™ characteristics Allocetra™ delivery into macrophages via engulfment Allocetra™ cell “eat me” signals PtdSer • Mononuclear cells collected from healthy donors Direct Gas6 Indirect
Slide 6: Allocetra for macrophage reprogramming: pipeline
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 Organ failure associated with Phase IIb Initiatied Completion of Phase $33B
Slide 7: 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 8: 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 Morality 50% Severe Organ Each year, at least 1.7 million adults in America 25% Damage Mortality develop sepsis. Nearly 270,000 Americans
Slide 9: 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 TREM-1 sTNFR1 Activation Inhibition Gro-α/β MCP-1 Chemotaxis Bacterial TNFα infection Downregulated in most of the patients IL
Slide 10: Phase Ib clinical trial of macrophage reprogramming in sepsis patients
AllocetraTM Phase Ib clinical trial of macrophage reprogramming in sepsis patients
Slide 11: 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 5000 IL-6 B 150 TNF-a C 20 IL-1b 3000 100 15 10 1000 50 5 900 50 5 700 40 4 TNF-⍺ pg/ml pg/ml IL-1-β pg/ml 500 IL-6 300 30 3 100 20 2 100 50 1
Slide 12: 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 IL-10 IL-1R⍺ G-CSF E F G 50 IL-10 40000 IL-1Ra 1000 G-CSF 30 800 20000 600 10 10 10000 300 8 250 pg/ml pg/ml pg/ml 7500 6 200 5000 150 4 100 2
Slide 13: 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's
Slide 14: 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 15: Allocetra macrophage reprogramming leads to improved outcomes for sepsis patients
Allocetra™ macrophage reprogramming leads to improved outcomes for sepsis patients Alive and organs recovered on day 28: 100% vs 41% Maximal change in SOFA score, diagnosis to day 28 # Total Controls 37 Patients Treated 10 Day 28 # % Controls 10 27% – Died Treated 0 0 – Alive Day 28 of SOFA Day 28 a
Slide 16: Statistically significant improvement in hospitalization and SOFA vs. matched controls
Allocetra™ macrophage reprogramming leads to improved outcomes for sepsis patients Statistically significant improvement in hospitalization and SOFA vs. matched controls Time to ICU discharge Average SOFA score during 28 days Drastic difference in organ failure resolution 5 4.4 4.1 4.1 4.0 4 3.47 Av
Slide 17: 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 18: Sepsis 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 Month
Slide 19: Phase Ib & II Clinical Trials in COVID-19
AllocetraTM Phase Ib & II Clinical Trials in COVID-19 Patients in Severe or Critical Condition
Slide 20: COVID-19 as a business segment
COVID-19 as a business segment • We believe COVID-19 will transfer from a pandemic state to an endemic state, and will remain a problem, although for a smaller population • The primary reasons: • Vaccine effectiveness less than 100% • 10-15% of vaccinated population do not show sufficient levels of
Slide 21: Positive Phase Ib and top line Phase II results in COVID-19
TM Allocetra : Positive Phase Ib and top line Phase II results in COVID-19 Hospitalization Clinical Outcome # Patients Post Administration of AllocetraTM Clinical Trial Disease Severity enrolled Recovered Mortality Discharged Duration Day 28 Day 28 Day 28 (days, avg.) Phase Ib 5 2 Severe, 3 Critical
Slide 22: Allocetra: COVID-19 regulatory pathway
TM Allocetra : COVID-19 regulatory pathway • Objective: obtain emergency/conditional approval for AllocetraTM in Europe, indicated for severe/critical patients • No guidance received from EMA re emergency/conditional approval in Europe • In the case AllocetraTM obtains emergency/conditional approval
Slide 23: Macrophage reprogramming in solid tumor microenvironment
AllocetraTM Macrophage reprogramming in solid tumor microenvironment Unique & differentiated value proposition
Slide 24: Tumor-associated macrophages: pro-tumor, immunosuppressive activities
Tumor-associated macrophages: pro-tumor, immunosuppressive activities Immunosuppressive functions1 • inhibit T cell, DC and NK cell activation • suppress anti-tumor T cell functions through inhibitory Direct pro-tumor functions • Promote resistance to therapy, angiogenesis, tumor cell survival and m
Slide 25: Effective solid cancer therapy requires changes to macrophages in the TME
Effective solid cancer therapy requires changes to macrophages in the TME Multiple strategies to kill or reprogram non-homeostatic, pro-tumor macrophages (TAMs)1 Kill or inhibit recruitment of TAMs Reprogram TAMs SIRPa inhibitors Trabectedin SIRP1a Immune checkpoints PD-L1 inhibitors Caspase 8 Bisph
Slide 26: The Enlivex differentiation: resident vs infiltrating macrophages
The Enlivex differentiation: Balance of resident macrophages vs bloodborne infiltrating macrophages and the effect on anti-tumor activity Cancer-induced changes to macrophage sub-populations: • Elimination of resident macrophages • Accumulation of pro-tumor TAMs originating from infiltrating macroph
Slide 27: Macrophage reprogramming in solid tumor microenvironment: Preclinical data
AllocetraTM Macrophage reprogramming in solid tumor microenvironment Preclinical data
Slide 28: Allocetra: reprogramming of peritoneal pro-tumor macrophages
Allocetra™: 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 1 6 12 18 24 30 40 Days 0 10 20 30 4
Slide 29: 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 100 HeLa-CD19 + CAR-T HeLa-CD19 + CAR-T + Allocetra-OTS 80 HeLa-CD19 + CAR-T + D89E_Allocetra-OTS % Survival 60 Complete remissi
Slide 30: The Enlivex differentiation: resident vs infiltrating macrophages
The Enlivex differentiation: Balance of resident macrophages vs bloodborne infiltrating macrophages and the effect on anti-tumor activity Cancer-induced changes to macrophage sub-populations: • Elimination of resident macrophages • Accumulation of pro-tumor TAMs originating from infiltrating macroph
Slide 31: Peritoneal cell clustering, additive effect of Allocetra on top of CAR-T
Peritoneal cell clustering, potential additive effect of Allocetra on top of CAR-T in different cell clusters Clusters 100% Percent of cells 50% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Bg-Hela CAR-T Mock CAR-T + Allocetra 31
Slide 32: Allocetra macrophage reprogramming research collaborations
Allocetra macrophage reprogramming research collaborations Collaborations aim to evaluate the potential of Allocetra™ in combination with immune-checkpoint inhibitors in solid cancer patients that do not respond to stand-alone checkpoint inhibitor therapies 32
Slide 33: Planned/executed milestones
Planned/executed milestones Q1 2021 Q3 2021 Q4 2021 or Q1 2022 Q2 2022 Top-line data from Phase IIb initiation; Interim data Top line data macrophage macrophage Designed to obtain macrophage reprogramming sepsis reprogramming COVID- Emergency-use designation reprogramming sepsis Phase IIb & Phase II
Slide 34: Financial Summary
Financial Summary NASDAQ GS ENLV Cash $90MM (Jun 30, 2020) Debt None Shares Outstanding 18.2 MM Funded Through Q1-2024 34
Slide 35: Management
Management Founder and President of PROLOR Biotech, Sold in 2013 ($560mm transaction). Lead product Shai Novik partnered to Pfizer, $295 million down payment, $275 upon FDA & other regulatory approvals. BLA filed Executive Chairman by Pfizer late 2020. Oren Hershkovitz Former Director of CMC, VP R&D
Slide 36: Board Of Directors
Board Of Directors Shai Novik Founder and President of PROLOR Biotech, Sold in 2013 ($560mm transaction). Lead product partnered to Pfizer, Executive Chairman $295 million down payment, $275 upon FDA & other regulatory approvals. BLA filed by Pfizer late 2020. Sangwoo Lee Executive Director of the I
Slide 37: Thank You
Thank You
Enlivex Therapeutics — Investor Presentation (August 2021) on 6ix