Ibio, Inc. · NASDAQ:IBIO
Ibio — Investor Presentation (April 2023)
46 slides from Ibio's investor presentation, Apr 24, 2023
Slide 1: AI-Powered Precision Antibody Therapeutics
ito Al-Powered Precision Antibody Therapeutics
Slide 2: Forward-looking Statements
Forward-looking Statements Certain statements in this presentation constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "may," "might," "will," "should," "believe," "expect," "anticipate," "estimate," "continue,
Slide 3: Executive Summary
EXECUTIVE SUMMARY iBio’s technology stack delivers precision antibodies designed to minimize downstream development risk through AI-guided epitope-steering and mAb optimization Patented* epitope-steering AI engine allows us to target specific regions of proteins The Ab-optimizing StableHu™ AI-Engine
Slide 4: Antibody Engineering is Hard: iBio's Precision AI Technology Provides 4 Solutions
Antibody Engineering is Hard: iBio’s Precision AI Technology Provides 4 Solutions Antibodies are built from stretches of amino acids, which are the words and sentences that make up the natural language of biology. We are using AI to decipher that language with a goal to explore novel biology and cre
Slide 5: AI Tech Stack Yields Precision-Targeted Antibodies with Lower Downstream Risk
AI Tech Stack Yields Precision-Targeted Antibodies with Lower Downstream Risk *U.S. Patent No. 11,545,238 (issued January 3, 2023) 5 Epitope Engineering Engine • Patented* epitope engineering • AI-engineered epitope maintains target structure Proprietary Antibody Library 3 StableHu™ Antibody Optimiz
Slide 6: Our Discovery Engine in Action
Our Discovery Engine in Action *U.S. Patent No. 11,545,238 (issued January 3, 2023) 6 1 AI-powered precision targeting of conformational & sub-dominant epitopes Epitope-specific antigens built to efficiently & selectively discover antibodies AI-generated naïve antibody library, free of sequence liab
Slide 7: Therapeutics Pipeline Growth and Maturation Driven Primarily by Cancer
Therapeutics Pipeline Growth and Maturation Driven Primarily by Cancer 7 Autoimmune PD-1 Autoimmune Disease s Solid Tumors Solid Tumors Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Oncology OPTIMIZATION Immunotherapies PROGRAMS EARLY
Slide 8: We Believe Our AI Platform Powers a Focused, Capital Efficient Business Plan
We Believe Our AI Platform Powers a Focused, Capital Efficient Business Plan 8 • Advancing a select few “fast followers” • Potential licensing and asset sales for other molecules • Partner existing molecules or discovery projects against new targets • Potential for upfront, milestone payments and/or
Slide 9: Potential Pipeline Value is Validated by Robust Early-Stage Deals
Potential Pipeline Value is Validated by Robust Early-Stage Deals 9 2018 SEP 2018 IBIO-101 (CD25) Roche / Tusk Therapeutics: $81M upfront, $758M total deal value 2019 2020 SEP 2020 CCR8 Gilead / Jounce: Original Deal: $85M upfront, $35M equity investment, $685M milestones 2023 Buyout by Gilead: $67M
Slide 10: IBIO-101 IL-2 Sparing Anti-CD25
IBIO-101 IL-2 Sparing Anti-CD25 10
Slide 11: IBIO-101 for Regulatory T-Cell (Treg) Depletion
IBIO-101 for Regulatory T-Cell (Treg) Depletion Recent Transactions PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT *Roche / Tusk Therapeutics (Sep, 2018) $81M upfront, $758M total deal value **Roche Ph1 Data (Apr, 2023) Well-tolerated: manageable safety profile Confirmed MOA: Red
Slide 12: IBIO-101 Reduces Tumor Growth in Preclinical Studies by Selectively Depleting Tregs
IBIO-101 Reduces Tumor Growth in Preclinical Studies by Selectively Depleting 1st Gen CD25 Immunosuppressive Tregs without Affecting Cancer Killing Teffs Blocked IL-2 pathways IL-2 CD25 (IL-2Rα) JAK JAK Treg JAK Teff JAK Indiscriminate depletion of Treg + Teff TUMOR 1 st gen CD25 mAbs depleted immun
Slide 13: IBIO-101 Selectively Depletes Tregs
IBIO-101 Selectively Depletes Tregs IBIO-101 potently binds recombinant CD25 while preserving IL-2 signaling which leads to Treg depletion while sparing Teffs RG6292 is Roche’s monoclonal antibody that targets CD25 (IL-2Rα). 13 IBIO-101 data on file.
Slide 14: IBIO-101 Increases Teff/Treg Ratio in Preclinical Studies Inhibiting Tumor Growth
IBIO-101 Increases in Teff/Treg Ratio in Preclinical Studies Inhibiting Tumor Growth Potently increases T-eff/T-reg ratio1 Tumor growth inhibition correlates with T-eff/T-reg ratio * Significant vs hIgG1 Isotype 1hCD25 animal model - Data on file. 14 * Significant vs Negative Control
Slide 15: IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy
IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy *hCD25 animal model - Data on file. 15 * Significant vs Negative Control # Significant vs Anti-PD-1 IBIO-101 + PD-1 Checkpoint Inhibitor In PreClinical Studies Enhances Tumor Suppression
Slide 16: IBIO-101 is an Antibody With Favorable Characteristics for CMC Development
IBIO-101 is an Antibody With Favorable Characteristics for CMC Development 16 Potential for Master Cell Bank (MCB) Development From 8 Promising Cell Lines Unoptimized Cell Lines Already Show Promising IBIO-101 Yields • Identified manufacturing partner to produce IBIO-101 for Phase 1&2 clinical trial
Slide 17: Anti-CCR8 High ADCC
Anti-CCR8 High ADCC Anti-CCR8 for the Depletion of T-regulatory Cells 17
Slide 18: CCR8 for Tumor-Infiltrating Treg Depletion
CCR8 for Tumor-Infiltrating Treg Depletion Recent Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT *Fibrogen / HiFiBio (Jun. & Dec. 2021): $25M option fee, $35M option exercise, $1.1B milestones **Gilead / Jounce (Dec. 2022): Original deal: $85M upfront, $
Slide 19: CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive
CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive Depletion of CCR8+ Treg cells has potential to evoke potent tumor immunity Zheng, et al. Cell 169.7 (2017): 1342-1356; Whiteside, et al. Immunology 163(4) (2021): 512-520; Kidani, et al. PNAS 119(7) (2022): e2114282119 19 CCR4+ cel
Slide 20: Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1 Antagonism and Cell Killing
Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1 Antagonism and CCR8-Specific Cell Killing Data on file 20 CCR8 overexpressed cell hCCR8 overexpressed cells hCCR4 overexpressed cells % of cell killing High Specificity CCR8 Cell Binding Potent binding to CCR8 overexpressing cells 10 8
Slide 21: Unlocking the Power of Bi-Specific Antibodies with Our Versatile CD3 mAb Panel
Unlocking the Power of Bi-Specific Antibodies with Our Versatile CD3 mAb Panel Wide Range of Affinities, Non-Human Primate (NHP) Cross Reactivity, High Developability 21
Slide 22: Next Generation Anti-CD3 T Cell Engagers
Next Generation Anti-CD3 T Cell Engagers Recent Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT *Eli Lilly / Merus (July 2021): $40M cash upfront, $20M investment, $540M milestones, plus royalties **Amgen / Teneobio (July 2021): $900M acquisition upfront,
Slide 23: CD3 T Cell Engager Panel Overcomes Key Challenges
CD3 T Cell Engager Panel Overcomes Key Challenges 23 Sequence Diversity 2 Hu-Cyno Cross-Reactivity 3 Range of Cytokine Release Broad CD3 activity for optimized paring with tumor antigen arms Risk reduction via cyno monkey toxicity study compatibility Tailored cytokine release for expanded therapeuti
Slide 24: Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies
Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies Data on file 24 Activation Binding Structural-Epitope Immunization & Screening StableHu Optimizer Hu/Cyno CD3 & T Cell T Cell ID 1 2 3 4 5 6 (-) Ctl Template 1 Template 2 2 Template Antibodies Optimized Antibodies TCR CD3 Engineered Epitopes
Slide 25: Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies
Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies Data on file 25 Library Screen: StableHu Mammalian-Display Epitope-Steered Immunization Human T Cell Binding High Medium Low Selected Hit Not Selected
Slide 26: CD3 Panel is Selected for a Diversity of T Cell Binding and Activation
CD3 Panel is Selected for a Diversity of T Cell Binding and Activation Data on file 26 T Cell Assay: EC50: 3 – 570 nM EC50: 2.5 – 70 nM Hit Clones Hit Clones Ab Concentration (nM) ID 1 2 3 4 5 (-) Ctl SP34 Gen1 benchmark SP34 Gen 1 benchmark Binding Activation Cytokines Human T Cell Binding EC50 (nM
Slide 27: Anti-EGFRvIII High ADCC
Anti-EGFRvIII High ADCC mAb Against Tumor-Specific EGFRvIII Cells 27
Slide 28: EGFRvIII for Glioblastoma and Other Cancers
EGFRvIII for Glioblastoma and Other Cancers Recent Transactions PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT *Seagen / LAVA Therapeutics (Sep. 2022): $50M upfront, $650M in milestones **Taiho / Cullinan Oncology (May 2022): $275M upfront, $130M in milestones *Seagen transaction
Slide 29: iBio's Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells
iBio’s Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells and Non EGFRvIII specific mAbs kill cancer cells but can cause toxicity by binding to EGFR1 in skin cells Not EGFR1-Expressing Cells in Healthy Tissues iBio mAb binding specifically to EGFRvIII Tumor Size Reduction Non-EGFRvIII
Slide 30: iBio's EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells
iBio’s EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells iBio EGFRvIII mAbs bind recombinant EGFRvIII but not binding wild-type EGFR1 which leads to tumor cell killing and thus not affecting healthy cells Data on file 30
Slide 31: Anti-MUC16 Tumor Associated Epitope
Anti-MUC16 Tumor Associated Epitope Non-Shed Epitope Anti-MUC16 Antibody 31
Slide 32: MUC16 Potential for Ovarian and Other Cancers
MUC16 Potential for Ovarian and Other Cancers 32 Recent Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT 2seventy – Regeneron (Jan 2022): CAR T 2023 IND planned Genentech (Sept 2021): ADC Ph. 1: Favorable safety & efficacy Eureka – Juno/BMS (Jan 2016): CAR
Slide 33: MUC16 Is Overexpressed and Shed by Tumor Cells
MUC16 Is Overexpressed and Shed by Tumor Cells 33 O-glycosylation N-glycosylation N-terminal and tandem repeat (TR) domains that are shed Tumor associated epitope that is not shed MUC16 epitope shedding Shedding eliminates the epitope and creates an antigen sink for most MUC16 antibodies Antibodies
Slide 34: Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding
Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding 34 Structural-epitope Immunization & Screening OVCAR-3 MUC16high Cell Binding Screen Engineered Epitope Prime + MUC16 Cell Boost higher cell binding Hybridoma Screen Weeks 1–2 MEM Nanoparticle Weeks 3–4 MUC16 Expressing Cells
Slide 35: Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope Closest to the Membrane
Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope Closest to the Membrane 35 N-terminal and tandem repeat (TR) domains that are shed Epitope time Hits do not bind shed 230-mer 1D7 8G4 21G6 Hits bind non-glycosylated non-shed 29-mer KD = 8.0 nM KD = 5.4 nM KD = 14 nM Aglycosylated non-shed
Slide 36: Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron Benchmark
Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron Benchmark 36 Clone ID: Unstained Secondary Only OVCAR-3 Cells 8G4 top clone higher cell binding Regeneron benchmark Mode Normalized
Slide 37: 8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in a Fully Human Framework
8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in a Fully Human Framework 37 8G4 with fully human framework reduces immunogenicity risk Cell binding OVCAR-3 Cells Iso. Ctl higher cell binding Glycosylated MUC16 membrane-proximal epitope SPR: KD = 5.1 nM Epitope binding
Slide 38: PD-1 Agonist Supports Restoration of Homeostasis for Inflammatory Diseases
PD-1 Agonist Supports Restoration of Homeostasis for Inflammatory Diseases 38
Slide 39: PD-1 Agonist to Alleviate Inflammatory Disease
PD-1 Agonist to Alleviate Inflammatory Disease 39 Recent transactions and milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT Merck / Pandion: Acquired for $1.85B (multiple assets, most advanced Ph 1a) Gilead / Mirobio: Acquired for $405M (two checkpoint agonists, most adva
Slide 40: Antagonizing PD-1 with PD-L1 Blocking Worsens Autoimmunity and Systemic Inflammation
Antagonizing PD-1 with PD-L1 Blocking Worsens Autoimmunity and Systemic Inflammation 40 Worsened Autoimmunity Increased & systemic inflammation Strong T-cell inhibition TCR MHC PD-1 PD-L1 Antigen presenting cell No T-cell inhibition T-cell PD-1 Antagonist Antibody Weak T-cell inhibition No T-cell in
Slide 41: Agonizing PD-1 Without Blocking PD-L1 Restores Activated T-Cell Suppression
Agonizing PD-1 Without Blocking PD-L1 Restores Activated T-Cell Suppression 41 Improved Autoimmunity Healthy Tissue Low-inflammation preserved Diseased Tissue Reduced inflammation Strong T-cell inhibition TCR MHC Strong T-cell inhibition PD-1 PD-L1 Antigen presenting cell T-cell PD-1 Agonist Antibod
Slide 42: In vitro PD-1 Agonism Equals or Surpasses Benchmarks and PD-L1
In vitro PD-1 Agonism Equals or Surpasses Benchmarks and PD-L1 Data on file 42 Ab ID EC50 (nM) SD-671823 0.88 SD-300670 0.31 SD-030629 0.36 SD-136366 0.28 SD-759028 0.52 SD-313018 (bispecific) 0.30 AnaptysBio APE12095 17.4 BMS/Celgene PD1AB6 0.76 IgG1 isotype control inactive AnaptysBio APE12095 BMS
Slide 43: Primary T-Cell Suppression Equals or Surpasses Benchmarks and PD-L1
Primary T-Cell Suppression Equals or Surpasses Benchmarks and PD-L1 Data on file 43 iBio Molecules Benchmark Molecules Natural Agonist Mean of 6 donors IL-2 at 24 hrs. 300 CD69 at 72 hrs. 200 200 100 Anti-HEL IgG1 Isotype Control 100 Anti-HEL IgG1 Isotype Control 0 0 Mean of 6 donors % IL-2 Release
Slide 44: In Summary
iBto In Summary 44
Slide 45: Our Leadership Team Brings Drug Discovery and Development Experience
Our Leadership Team Brings Drug Discovery and Development Experience Martin Brenner, DVM, Ph.D. Interim CEO & CSO Felipe Duran Interim CFO Marc Banjak GC Lisa Middlebrook CHRO 45
Slide 46: Summary
Summary Pipeline of difficult to find biologics • Pipeline of 10 preclinical primarily immuno-oncology (I/O) biologics • Targets have been of interest to major I/O companies • Lead asset (IBIO-101) is a next-generation anti-CD25 (fast follower to Roche’s RG6292) • IBIO-101 CMC development is underwa