Ibio, Inc. · NASDAQ:IBIO
Ibio — Investor Presentation (October 2023)
53 slides from Ibio's investor presentation, Oct 2, 2023
Slide 1: AI-Powered Precision Antibody Therapeutics
October 2023 AI-Powered Precision Antibody Therapeutics
Slide 2: Forward-looking Statements
2 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," "continu
Slide 3: Executive Summary
* U.S. Patent No. 11,545,238 iBio’s technology stack delivers precision antibodies designed to minimize downstream development risk through AI-guided epitope-steering and mAb optimization 3 Patented* epitope-steering AI-engine allows us to target specific regions of proteins Ab-optimizing StableHu™
Slide 4: Harnessing iBio's Tech Stack: From Precision Antibody Identification to Tailored Bispecifics
• Patented* epitope engineering • AI-engineered epitope maintains target structure 1 Epitope Engineering *U.S. Patent No. 11,545,238 (issued January 3, 2023) 4 Harnessing iBio’s Tech Stack: From Precision Antibody Identification and Optimization to Tailored Bispecifics Multiple validations with diff
Slide 5: AI Epitope Engine: Engineered Epitopes Generalizable to Complex Drug Binding Sites
Match Engineered Structure to Target Refined for Greater Stability Optimized for Water Solubility Unlocking High-Value Drug Targets: AI-Engineered Epitopes are Generalizable to a Broad Set of Complex Structural Drug Binding Sites Junctional Epitopes Complex Secondary Structures Membrane Proteins (e.
Slide 6: StableHu Antibody Optimization & Mammalian Display Screening
Input Antibody StableHu AI-Engine Mammalian Display Output Antibody Template CDR Predict library of human CDR variants Single-cell screen mammalian display CDR library Optimized antibody with fully human CDRs Accelerate Success: StableHu Antibody Optimization & Mammalian Display Screening Propel Fas
Slide 7: EngageTx CD3-Based T-Cell Engager Panel
7 EngageTx, a CD3-Based T-Cell Engager Panel, Addresses 3 Key Challenges: Cytokine Release, NHP Cross-Reactivity and Immunogenicity Risk Numerous tumor antigen arms Diverse CD3 engager arms 1 Sequence Diversity 2 Hu-Cyno Cross-Reactivity 3 Range of Cytokine Release Increased humanness and broad CD3
Slide 8: From Idea To Clinical Candidate: Discovery Platform
8 From Idea To Clinical Candidate: We Believe Our Discovery Platform Improves Probability of Success, Speed, and Developability AI-powered sequence optimization to improve performance AI-powered precision targeting of conformational & sub-dominant epitopes Epitope-specific antigens built to efficien
Slide 9: Capitalizing on AI: Focused, Capital Efficient Business Plan
Capitalizing on AI: We Believe Our Platform Powers a Focused, Capital Efficient Business Plan 9 AI Discovery Platform • Partner existing molecules or discovery projects against new targets • Potential for upfront, milestone payments and/or royalties Strategic Partnerships • Advancing a select few “f
Slide 10: Catalyzing Innovation: Technology Stack Spurs Rapid Pipeline Growth
PROGRAMS EARLY DISCOVERY LATE DISCOVERY LEAD OPTIMIZATION IND-ENABLING CLINICAL Oncology IBIO-101 Trop-2 x CD3* MUC16 Target 5 EGFRvIII CCR8 Target 8 Autoimmune PD-1 10 Catalyzing Innovation: Technology Stack Spurs Rapid Pipeline Growth and Maturation in Cancer Immunotherapies Immuno-Oncology Immuno
Slide 11: Market-Tested Potential: Competitor Early-Stage Deals
* Acquisition / Merger + License or collaboration 11 Market-Tested Potential: Competitor Early-Stage Deals Signal Promising Opportunities for Our Pipeline FEB 2021 Pre-2019 2020 2021 2022 CCR8 Gilead / Jounce+: $85M upfront, $35M equity investment, $685M milestones SEP 2020 PD-1 agonist Merck / Pand
Slide 12: iBio Company Highlights
12 iBio Company Highlights • Ticker: IBIO (NYSE A); ~27.6M shares outstanding as of 6/30/23 • Reduced costs by ~67% post CDMO divestment from FY 23 Q1 to Q4 • Significantly reduced debt upon consummation of facility sale Financial AI-driven discovery tech stack • Patented epitope-engineering technol
Slide 13: Preclinical Pipeline
Preclinical Pipeline 13
Slide 14: IBIO-101 IL-2 Sparing Anti-CD25
14 IBIO-101 IL-2 Sparing Anti-CD25
Slide 15: IBIO-101 for Regulatory T-Cell (Treg) Depletion
Recent Transactions & Milestones *Roche acquisition of Tusk Therapeutics completed for €70M upfront, acquiring worldwide rights to anti-CD25 program. Values converted to dollars as reported in public press releases **Data presented by Roche at AACR 2023 15 IBIO-101 for Regulatory T-Cell (Treg) Deple
Slide 16: IBIO-101 Reduces Tumor Growth by Selectively Depleting Tregs
Data on file. Treg = Regulatory T Cells; Teff = Effector T Cells; ADCC = Antibody Dependent Cellular Cytotoxicity 16 IBIO-101 Reduces Tumor Growth in Preclinical Studies by Selectively Depleting Immunosuppressive Tregs without Affecting Cancer Killing Teffs Indiscriminate depletion of Treg + Teff TU
Slide 17: IBIO-101 Selectively Depletes Tregs while Preserving IL-2 Signaling
RG6292 is Roche’s monoclonal antibody that targets CD25 (IL-2Rα). IBIO-101 data on file. 17 IBIO-101 Selectively Depletes Tregs while preserving IL-2 signaling IBIO-101 potently binds recombinant CD25 which leads to Treg depletion while sparing Teffs
Slide 18: IBIO-101 Increases Teff/Treg Ratio Inhibiting Tumor Growth
18 IBIO-101 Increases in Teff/Treg Ratio in Preclinical Studies Inhibiting Tumor Growth Tumor growth inhibition correlates with T-eff/T-reg ratio Potently increases T-eff/T-reg ratio1 1hCD25 animal model - Data on file. * Significant vs * Significant vs Negative Control hIgG1 Isotype
Slide 19: IBIO-101 in Combination With a Checkpoint Inhibitor
19 IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy IBIO-101 + PD-1 Checkpoint Inhibitor In PreClinical Studies Enhances Tumor Suppression *hCD25 animal model - Data on file. * Significant vs Negative Control # Significant vs Anti-PD-1
Slide 20: IBIO-101 Favorable Characteristics for CMC Development
20 IBIO-101 is an Antibody With Favorable Characteristics for CMC Development • Identified manufacturing partner to produce IBIO-101 for Phase 1&2 clinical trials • Discovered suitable cell lines for manufacturing MCB • Established IBIO-101 CMC methodology for producing high yield, high purity, stab
Slide 21: Anti-CCR8 High ADCC
21 Anti-CCR8 High ADCC Anti-CCR8 for the Depletion of T-regulatory Cells
Slide 22: CCR8 for Tumor-Infiltrating Treg Depletion
*Fibrogen / HiFiBio: Fibrogen purchased option to multiple programs in June 2021, then exercised the option for excl. license to CCR8 program in Dec. 2021. **Gilead / Jounce: Exclusive worldwide license to anti-CCR8 antibody. *** Coherus / Surface Oncology: acquisition, announced in June 2023, adds
Slide 23: CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive
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 23 CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive Depletion of CCR8+ Treg cells has potential to evoke potent tumor immunity • Systemi
Slide 24: Afucosylated Anti-CCR8 Antibody Exhibits High Specificity and Cell Killing
Data on file 24 Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1 Antagonism and CCR8-Specific Cell Killing High Specificity CCR8 Cell Binding 0.0001 0.001 0.01 0.1 1 10 0 2 4 6 8 10 hCCR8 overexpressed cells Ab. (nM) MFI hIgG1 isotype mIgG2A isotype Anti -hCCR4 - EC50 = NA Anti-mCCR8
Slide 25: CCR8-Specific High ADCC Antibody Induces Tumor Regression
25 iBio’s CCR8-Specific High ADCC Antibody Induces Tumor Regression in a Transgenic Human CCR8 Mouse Model Day -7 Day 0 Day 0, 3, 7, 10 Tumor implantation Subsequent dosing Test article dosing (i.p) 0 2 4 6 8 10 12 14 0 50 100 150 200 250 300 Days after treatment Tumor Volume (mm3 ) * * * * p<0.05 v
Slide 26: EngageTx, Our Versatile CD3 mAb Panel
26 Unlocking the Power of Bi-Specific Antibodies with EngageTx, Our Versatile CD3 mAb Panel Wide Range of Affinities, NHP Cross Reactivity, High Developability
Slide 27: Next Generation Anti-CD3 T Cell Engagers
*Eli Lilly / Merus: Fibrogen Research collaboration using Merus’ proprietary platform to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies. ** GSK WuXi: License of WuXi’s preclininical CD3 bi-specific, plus 3 earlier stage programs ***Amgen / Teneobio: Teneobio was d
Slide 28: Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies
Data on file 28 Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies Hu/Cyno CD3 & T Cell TCR CD3 Engineered Epitopes T Cell Template 1 Template 2 Structural-Epitope Immunization & Screening StableHu Optimizer AI Discovery Engine AI-Engineered Immunogens Epitope & T Cell Immunization Epitope &
Slide 29: Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies
Data on file 29 Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies Epitope-Steered Immunization Human T Cell Binding Selected Hit Low Medium High StableHu Mammalian-Display Not Selected Library Screen:
Slide 30: EngageTx Selected for Diversity of T Cell Binding and Activation
Data on file 30 EngageTx is Selected for a Diversity of T Cell Binding and Activation EC50: 3 – 570 nM EC50: 2.5 – 70 nM Human T Cell Binding EC50 (nM) CD69 T Cell Activation EC50 (nM) Hit Clones Hit Clones T Cell Assay: Ab Concentration (nM) IFN-γ (pg/mL) TNF-⍺ (pg/mL) IL-2 (pg/mL) ID 1 2 3 5 (-) C
Slide 31: Anti-EGFRvIII High ADCC mAb
31 Anti-EGFRvIII High ADCC mAb Against Tumor-Specific EGFRvIII Cells
Slide 32: EGFRvIII for Glioblastoma and Other Cancers
**Seagen / LAVA Therapeutics (Sep 2022): $50M upfront, $650M milestones ***Taiho / Cullinan Oncology (May 2022): $275M upfront, $130M milestones * Pierre Fabre / Scorpion: Scorpion licensed two preclinical-stage programs to Pierre Fabre which are targeted to specific EGFR mutations in lung cancer. *
Slide 33: Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells
Skin toxicity No skin damage 33 iBio’s Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells and Not EGFR1-Expressing Cells in Healthy Tissues iBio mAb binding specifically to EGFRvIII Tumor Size Reduction iBio mAb doesn’t bind to EGFR1 in skin Non-EGFRvIII specific mAb binds to EGFR1 in
Slide 34: EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells
34 iBio’s EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells iBio EGFRvIII mAbs bind recombinant EGFRvIII which leads to tumor cell killing but not binding wild-type EGFR1 and thus not affecting healthy cells Data on file
Slide 35: EGFRvIII-Specific High-ADCC Antibody Inhibits Tumor Growth in Xenograft Model
35 iBio’s EGFRvIII-Specific High-ADCC Antibody Inhibits Tumor Growth in an EGFRvIII Tumor Xenograft Mouse Model Day -7 Day 0 Day 0, 3, 8, 11, 14, 17 Tumor implantation Subsequent dosing Test article dosing (i.v.) 0 5 10 15 20 25 0 200 400 600 800 1000 1200 1400 1600 1800 Days after treatment Tumor V
Slide 36: Anti-MUC16
36 Anti-MUC16 Tumor Associated Epitope Non-Shed Epitope Anti-MUC16 Antibody
Slide 37: MUC16 Potential for Ovarian and Other Cancers
+Regeneron MUC16xCD3 (Sept 2022): Ph. 1 31% ORR Ph. 2 enrollment 37 MUC16 Potential for Ovarian and Other Cancers Bind a membrane-proximal MUC16 epitope Membrane-proximal binding avoids epitope elimination by tumors Bind a non-glycosylated epitope to avoid altered glycosylation on tumors • Ovarian •
Slide 38: MUC16 Is Overexpressed and Shed by Tumor Cells
38 MUC16 Is Overexpressed and Shed by Tumor Cells O-glycosylation N-glycosylation MUC16 epitope shedding Shedding eliminates the epitope and creates an antigen sink for most MUC16 antibodies Antibodies that bind the non-shed domain maintain activity N-terminal and tandem repeat (TR) domains that are
Slide 39: Immunizations Steered to a MUC16 Epitope that Avoids Shedding
Weeks 1–2 Weeks 3–4 Week 5 39 Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding Engineered Epitope Prime + MUC16 Cell Boost AI Discovery Engine MUC16 Engineered Epitope Structural-epitope Immunization & Screening Engineered Epitope ELISA Screen MUC16 OVCAR-3 MUC16high Cell B
Slide 40: Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope
40 Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope Closest to the Membrane 1D7 8G4 21G6 Hits do not bind shed 230-mer Hits bind non-glycosylated non-shed 29-mer binding time O-glycosylation N-glycosylation N-terminal and tandem repeat (TR) domains that are shed Epitope KD = 8.0 nM KD =
Slide 41: Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Benchmark
41 Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron Benchmark Regeneron benchmark Clone ID: Secondary Only Unstained OVCAR-3 Cells 8G4 top clone higher cell binding Mode Normalized Data on file
Slide 42: 8G4 Clone Maintains Binding in a Fully Human Framework
42 8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in a Fully Human Framework 8G4 with fully human framework reduces immunogenicity risk Glycosylated MUC16 membrane-proximal epitope SPR: KD = 5.1 nM Iso. Ctl OVCAR-3 Cells Epitope binding Cell binding higher cell binding Data on file
Slide 43: Anti-Trop-2 x CD3 Bi-Specific Antibody
43 Anti-Trop-2 x CD3 Bi-Specific Antibody against Tumor-Specific Trop-2 Cancer Cells
Slide 44: Trop-2 x CD3 Bi-Specific Antibody for Head & Neck and Others
Recent transactions Target mechanism Potential indications Differentiation / opportunity Gilead acquired Immunomedics (Sept 2020): $21Bn Payment Trodelvy: Approval 44 Trop-2 x CD3 Bi-Specific Antibody for Head & Neck and Others Cancer Select killing cancer cells that up-regulate Trop-2 expression wh
Slide 45: Trop-2 x CD3 Bi-Specific Antibody Selective Target
Tumor cells show significantly increased Trop-2 expression Tumor cell death with high Trop-2 expression Trop-2 x CD3 binds to tumor cells Trop-2 x CD3 recruits T cells to kill tumor cells 45 Trop-2 x CD3 Bi-Specific Antibody Selective Target Overexpress Trop-2 Cancer Cells Trop-2 Tumor cell Healthy
Slide 46: Trop-2 x CD3 Potently Kills Tumor Cells with Low Cytokine Release
46 iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low Cytokine Release 46 0.0001 0.001 0.01 0.1 1 10 0 20 40 60 80 100 Ab (nM) % of Cell Killing ID EC50 (pM) Cmax (% killing) SD-753019 1.4 92% SD-231831 7.2 92% SD-753019 (Trop-2 x CD3SP34 Gen1) SD-231831 (Trop-2 x CD3iBio)
Slide 47: Single Dose Induces Tumor Regression in Humanized Mouse Model
47 A Single Dose of iBio’s Bispecific Trop-2 x CD3 Antibody Induces Tumor Regression in a Humanized Mouse Cancer Model 0 7 14 0 50 100 150 200 250 Days after tumor implantation Tumor volume (mm 3 ) Vehicle SD-231831 (1 mg/kg) Trop-2 x CD3iBio * * * * p<0.05 vs vehicle Single dose SD-231831 36% tumor
Slide 48: PD-1 Agonist Supports Restoration of Homeostasis for Inflammatory Diseases
48 PD-1 Agonist Supports Restoration of Homeostasis for Inflammatory Diseases
Slide 49: PD-1 Agonist to Alleviate Inflammatory Disease
49 PD-1 Agonist to Alleviate Inflammatory Disease Selectively agonize PD-1 without antagonizing the natural PD-1:PD-L1 anti-inflammatory interaction • Rheumatoid arthritis • Broad application in treating inflammatory disease Target mechanism Potential indications Differentiation / opportunity Recent
Slide 50: Antagonizing PD-1 Worsens Autoimmunity and Systemic Inflammation
PD-1 PD-L1 TCR MHC T-cell Antigen presenting cell 50 Antagonizing PD-1 with PD-L1 Blocking Worsens Autoimmunity and Systemic Inflammation Inflammatory Disease Tissue Healthy Tissue Increased & systemic inflammation No T-cell inhibition No T-cell inhibition Worsened Strong T-cell inhibition Weak T-ce
Slide 51: Agonizing PD-1 Without Blocking PD-L1 Restores T-Cell Suppression
51 Agonizing PD-1 Without Blocking PD-L1 Restores Activated T-Cell Suppression Diseased Tissue Reduced inflammation Healthy Tissue Low-inflammation preserved PD-1 PD-L1 Strong TCR MHC T-cell inhibition T-cell Inflammatory Disease Tissue Healthy Tissue Weak T-cell inhibition Strong T-cell inhibition
Slide 52: In vitro PD-1 Agonism Equals or Surpasses Benchmarks
Benchmark Antibodies PD-1 Agonist Antibodies 52 In vitro PD-1 Agonism Equals or Surpasses Benchmarks and PD-L1 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
Slide 53: Primary T-Cell Suppression Equals or Surpasses Benchmarks
Data on file 53 Primary T-Cell Suppression Equals or Surpasses Benchmarks and PD-L1 IL-2 at 24 hrs. % IL-2 Release Mean of 6 donors 0 100 200 Anti-HEL IgG1 Isotype Control CD69 at 72 hrs. CD69 MFI Mean of 6 donors 0 100 200 300 Anti-HEL IgG1 Isotype Control iBio Molecules Benchmark Molecules Natural