Ibio, Inc. · NASDAQ:IBIO
Ibio — Investor Presentation (April 2025)
87 slides from Ibio's investor presentation, Apr 8, 2025
Slide 1: Breakthrough Antibodies for Obesity and Cardiometabolic Diseases
Breakthrough Antibodies for Obesity and Cardiometabolic Diseases Enabled by an AI-Platform Scalable for Future High-Value Indications Corporate Presentation April 2025
Slide 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," "continue," "predict," "forecast," "
Slide 3: An Antibody Discovery Platform for Cardiometabolic Disease and Beyond
3 An Antibody (Ab) Discovery Platform for Cardiometabolic Disease and Beyond Advancing Antibodies Against Difficult Targets With an Integrated and Validated AI Technology Stack Apply 2026 Obesity programs advance into clinic Scale 2029 Obesity programs advance to late clinical development Assets in
Slide 4: iBio's AI-Driven Antibody Discovery Platform Has Delivered
iBio's AI-Driven Antibody Discovery Platform Has Delivered Corporate Highlights • AI-driven antibody discovery Platform including patented Epitope steering, StableHu , EngageTx , and ShieldTx® • Platform has delivered Development Candidates in as little as 7 months • 11 active programs: 5 Cardiometa
Slide 5: Any Epitope on Any Drug Target
Any Epitope on Any Drug Target AI Epitope Engineering and Antibody Optimization Engines unlock challenging target classes • Multi-layer technology platform addresses multiple challenges in Ab discovery • Patented Epitope Steering technology • Single-step Ab StableHu x Mammalian Display • Masked (Shi
Slide 6: iBio's AI Tech Stack is a Fully Integrated Solution
6 iBio’s AI Tech Stack is a Fully Integrated Solution for Antibody Discovery Enables and accelerates Antibody Discovery & Development Against Hard-to-Drug Targets
Slide 7: Harnessing the Power of Our Platform in Cardio-metabolic Disease
Transition slide – Harnessing the Power of Our Platform to Address Challenges in Cardio-metabolic Disease
Slide 8: iBio's Obesity and Cardiometabolic Pipeline
8 iBio’s Rapidly Advancing High Value Obesity and Cardiometabolic Pipeline Therapeutic Area Program Early Discovery Late Discovery Lead Optimization IND-Enabling Cardio-metabolic IBIO-600 Myostatin (obesity) Myostatin x Activin A (obesity/ potentially PH-HFpEF) Activin E (obesity) Target 3 (obesity)
Slide 9: Current Treatments in Obesity Fall Short
9 Current Treatments in Obesity Fall Short Significant Unmet Medical Need for Innovation to Improve Overall Metabolic Health and Function The Next Generation Potential Avenues: • Preservation of muscle mass during GLP-1 agonist induced weight loss • Improved fat burning and prevention of dyslipidemi
Slide 10: A Clear Strategy to Create a High-Value Pipeline
10 A Clear Strategy to Create a High-Value Pipeline of Differentiated Products A prime opportunity exists for GLP-1 complementary therapeutic approaches • Muscle mass loss • Side effects leading to discontinuation • Inconvenient dosing frequency • Room for high quality weight loss Address Challenges
Slide 11: IBIO-600 Long-Acting Anti-Myostatin Antibody
Transition slide – IBIO-600 Long-Acting Anti-Myostatin Antibody
Slide 12: Myostatin Antagonism
1. Schuelke M. (2004). New England Journal of Medicine 350(2682–2688). 2. Deng, B. (2017). Nutrition and Metabolism, 14(29). 12 Myostatin Antagonism Enhancing the Quality of Weight Loss by Maintaining Muscle Mass During and After Weight Loss with GLP-1s We are developing Myostatin inhibitors to pres
Slide 13: IBIO-600: A Long-Acting First-in-Class Anti-Myostatin Antibody
1. Data on file IBIO-600: A Long-Acting First-in-Class Anti-Myostatin Antibody First Anti-Myostatin Antibody With a Target Product Profile Specifically Tailored for an Obese Patient Population IBIO-600 Long-Acting Anti-Myostatin Antibody First-in-class innovation: First Myostatin therapy tailored fo
Slide 14: IBIO-600 Increases Muscle Differentiation in Human Myoblast Cells
14 IBIO-600 Increases Muscle Differentiation in Primary Human Myoblast Cells Red indicates muscle cell growth and development (as measured by myoblast differentiation) Myostatin Only Myostatin + IBIO-600 IBIO-600 potently increases myoblast differentiation Baseline human myoblast differentiation (un
Slide 15: Interim Data: IBIO-600 Preserves Muscle Mass in GLP-1 Treated Mice
Body weight loss up to day 14 In this study the murine surrogate antibody of IBIO-600 was used 15 Interim Data: IBIO-600 Preserves Muscle Mass in GLP-1 Treated Diet Induced Obesity Mice Day 14 Interim Data Collection Day -7 Day 1 Day 28 Day 56 Body composition Insulin tolerance test Grip Strength St
Slide 16: IBIO-600 Pharmacokinetics Study in Non-Human Primates
16 IBIO-600 Pharmacokinetics (PK) Study in Non-Human Primates (NHPs) Week -4 Week -2 Week 2 Week 6 PK monitoring DEXA scan Week 4 DEXA scan Week 8 DEXA scan Week 0 I.V. Dose Study details Study design • Obese, aged NHPs • Performed at Kunming Biomed International (KBI) • Material produced transientl
Slide 17: IBIO-600 Fc Engineering Drives Extended Half-Life in Obese NHPs
1. Linear elimination phase used to estimate half-life with simple linear model 17 IBIO-600 Fc Engineering Drives Extended Half-Life in Obese NHPs Dose t1/2 (days) 5 mg/kg 52.4 50 mg/kg 40.7 IBIO-600 Fc engineering results in enhanced FcRn binding Clone Fc Fold increase over standard IgG IBIO-600 FA
Slide 18: Allometric Scaling Suggests Extended Half-Life in Humans
. 1 https://pmc.ncbi.nlm.nih.gov/articles/PMC9709760/#CR37 2 https://www.jstage.jst.go.jp/article/bpb/43/5/43_b19-01042/_html/-char/en 18 Allometric Scaling Suggests Meaningfully Extended Half-Life for IBIO-600 in Humans Y=2.49x+17 0 10 20 30 0 20 40 60 80 100 Allometric scaling YTE and LS mAb only
Slide 19: Lean Mass Remains Elevated at 12 Weeks After Single Injection
Data on file 19 Lean Mass Peaks at 8 Weeks Remains Elevated at 12 Weeks After a Single IBIO-600 i.v. Injection Baseline Week 4 Week 8 Week 12 -500 0 500 Single dose 5 mg/kg Change in lean mass (g, from baseline) Baseline Week 4 Week 8 Week 12 -500 0 500 Single dose 50 mg/kg Change in lean mass (g, f
Slide 20: Fat Mass Reduced After a Single I.V. Dose of IBIO-600
20 Fat Mass between Thigh and Abdomen is Reduced After a Single I.V. Dose of IBIO-600 Baseline Week 4 Week 8 Week 12 -500 0 500 Single dose 5 mg/kg Change in fat mass (g, from baseline) Baseline Week 4 Week 8 Week 12 -500 0 500 Single dose 50 mg/kg Change in fat mass (g, from baseline) Baseline Week
Slide 21: Anti-Activin E Antibody
Anti-Activin E Antibody
Slide 22: Activin E Antagonism
Type 2 Diabetes (T2D) 22 Activin E Antagonism Attractive Fat-Specific Weight Loss Mechanism with Excellent Compatibility for Bi-Specific Pairing with Anti-Myostatin We are developing inhibitors of Activin E to promote fat-specific weight loss, either as a standalone drug or as a bi-specific antibody
Slide 23: First-in-Class Functional Antibody for Activin E
• First-in-class functional antibody for Activin E iBio’s AI-Enabled Epitope Steering Engine Bypasses Recombinant Activin E, Creating Functional Antibodies Directly from the Target Sequence Activin E Antibody AI epitope engineering breaks barrier to discovery Innovative AI solution: Epitope steering
Slide 24: AI Epitope Engine Delivers First-in-Class Functional Activin E Antibody
24 iBio’s AI Engineered Epitope Engine Delivers a First-in-Class Functional Activin E Antibody Challenge We have uniquely solved an industry-wide problem with our proprietary epitope engineering engine to create functional Activin E antibodies iBio’s Solution Breakthrough Activin E Signaling (lower
Slide 25: Preclinical Study: Activin E Antibody With GLP-1 in Obese Mice
25 Preclinical Study: Activin E Antibody in Combination With GLP-1 in Diet-Induced Obese Mice Study Details • Activin E mAb: Mouse IgG1, human VH and VL • Semaglutide: 40ug/kg (mimics human dose), daily • iBio Activin E mAb: 10mg/kg, 2x/week • Body composition (DEXA) and multiple terminal endpoints
Slide 26: Interim Data: Activin E Antibody Causes Fat-Specific Weight Loss
Data on File 26 2 Week Interim Data: Activin E Antibody Alone and in Combination with GLP-1Causes Fat-Specific Weight Loss Body weight change (2-week interim data) Baseline Week 2 0 5 10 15 20 Fat Mass (g) Fat Mass (g) Veh/Veh Veh/mAb Sema/Veh Sema/mAb
Slide 27: Anti-Myostatin x Activin A Bispecific Antibody
Transition slide – Anti-Myostatin x Activin A Bispecific Antibody
Slide 28: Combined Myostatin and Activin A Antagonism
28 Combined Myostatin and Activin A Antagonism Synergistic Effect on Muscle Growth and Potential Treatment for Pulmonary Hypertension (PH) in Heart Failure With Preserved Ejection Fraction (HFpEF) For obesity, we are developing bi-specific co-inhibitors of Myostatin and Activin A to enhance muscle g
Slide 29: Long-Acting First-in-Class Anti-Myostatin x Activin A Bispecific
• Well-tolerated for long-term use • Infrequent subcutaneous self-administration *Bone Morphogenetic Proteins A Long-Acting First-in-Class Anti-Myostatin x Activin A Bispecific Antibody Myostatin x Activin A Bi-specific Target product profile for obese and potentially Ph-HFpEF patients First-in-clas
Slide 30: Bi-Specific Targets Both Key Negative Muscle Regulators
30 iBio’s Myostatin and Activin A Bi-Specific Targets Both Key Negative Muscle Regulators, Synergistically Increasing Muscle Mass Increased muscle fusion index in human muscle stem cells is a surrogate of muscle growth Negative control (Myostatin + Activin A) without antibody Myostatin + Activin A w
Slide 31: Immuno-Oncology
Immuno-Oncology
Slide 32: Beyond Cardiometabolic – Our Oncology Pipeline
*Tumor Micro Environment 32 Beyond Cardiometabolic – Driving Value Within Our Oncology Pipeline Program MoA Potential Indications Early Discovery Late Discovery Lead Optimization IND-Enabling Highlights IBIO-101 Treg depletion, IL-2 sparing Solid tumors, orphan indications Synergistic efficacy with
Slide 33: A Leadership Team with Deep Industry Experience
33 A Leadership Team with Deep Industry Experience Deep expertise in cardiometabolic disorders Marc Banjak CLO Martin Brenner, DVM, Ph.D. CEO & CSO Kristi Sarno Senior VP BD Felipe Duran CFO
Slide 34: Executive Summary
Executive Summary Corporate Highlights • Patented AI-driven Discovery Tech Stack which can: • Rapidly advance a highly developable pre-clinical pipeline • Solve hard-to-drug problems • Pipeline of cardio/obesity rapidly progressing • Pipeline of immuno-oncology molecules ready for strategic partners
Slide 35: Appendix
Appendix
Slide 36: Technology Platform & Preclinical Pipeline
36 Technology Platform & Preclinical Pipeline
Slide 37: Technology Stack
37 Technology Stack
Slide 38: iBio's Tech Stack Aims to Solve Major Challenges in Antibody Discovery
38 iBio’s Tech Stack Aims to Solve Major Challenges in Antibody Discovery & Development Epitope Steering StableHu & Mammalian Display Unlocking Novel Biology Reduced Lead-Optimization Time Optimization in less than 4 weeks Minimized Developability Risk Mammalian Display in Manufacturing Cell Line Po
Slide 39: Tech Stack Addresses Immuno-oncology Challenges
39 iBio’s Tech Stack Addresses Immuno-oncology Discovery and Development Challenges ShieldTx 2nd Gen T-cell Engager Panel Finely tuned T-cell engagement Adjustable T-cell engagement to fit any tumor target engager Improved safety prediction Cyno cross reactivity allows for better preclinical safety
Slide 40: Unlocking High-Value Drug Targets: AI-Engineered Epitopes
Match Engineered Structure to Target Refined for Greater Stability Optimized for Water Solubility 40 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
Slide 41: 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 41 Accelerate Success: StableHu Antibody Optimization & Mammalian Display Screening Propel
Slide 42: ShieldTx Conditionally Activated Antibodies
42 “Smart” Antibodies: ShieldTx Conditionally Activated Antibodies Strive to Improve Safety by Selectively Targeting Diseased but not Healthy Tissue H+ Diseased Tissue “On-epitope, off-tissue” therapy Healthy Tissue “On-epitope, on-tissue” therapy DME activation Diseased Tissue “On epitope, on tissu
Slide 43: EngageTx CD3-Based T-Cell Engager Panel
43 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 44: Platform Tackles Discovery Challenges for the Next Era of Antibodies
Epitope Engineering Engine* Proprietary Antibody Library AI-powered mammalian-display co-optimization of mono/multi-specific antibody and conditionally activated mask Engineered Epitope Steering AI-powered engineering of conformational epitopes Epitope-specific antigens that steer discovery to inten
Slide 45: IBIO-101 IL-2 Sparing Anti-CD25
45 IBIO-101 IL-2 Sparing Anti-CD25
Slide 46: IBIO-101 for Regulatory T-Cell 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 46 IBIO-101 for Regulatory T-Cell (Treg) Deple
Slide 47: IBIO-101 Selectively Depletes Immunosuppressive Tregs
Data on file. Treg = Regulatory T Cells; Teff = Effector T Cells; ADCC = Antibody Dependent Cellular Cytotoxicity 47 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 48: 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. 48 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 49: IBIO-101 Increases Teff/Treg Ratio in Preclinical Studies
1hCD25 animal model - Data on file. 49 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 * Significant vs * Significant vs Negative Control hIgG1 Isotype
Slide 50: IBIO-101 With Checkpoint Inhibitor Shows Greater Efficacy
*hCD25 animal model - Data on file. 50 IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy IBIO-101 + PD-1 Checkpoint Inhibitor In PreClinical Studies Enhances Tumor Suppression * Significant vs Negative Control # Significant vs Anti-PD-1
Slide 51: Anti-CCR8 High ADCC
51 Anti-CCR8 High ADCC Anti -CCR8 for the Depletion of T-regulatory Cells
Slide 52: 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 53: 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 53 CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive Depletion of CCR8+ Treg cells has potential to evoke potent tumor immunity • Systemi
Slide 54: Afucosylated Anti-CCR8 Antibody Exhibits High Specificity
Data on file 54 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 55: CCR8 Antibody Induces Tumor Regression in Mouse Model
55 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 56: EngageTx, Our Versatile CD3 mAb Panel
56 Unlocking the Power of Bi-Specific Antibodies with EngageTx, Our Versatile CD3 mAb Panel Wide Range of Affinities, NHP Cross Reactivity, High Developability
Slide 57: 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 preclinical CD3 bi-specific, plus 3 earlier stage programs ***Amgen / Teneobio: Teneobio was dev
Slide 58: Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies
Data on file 58 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 59: Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies
Data on file 59 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 60: EngageTx Selected for Diversity of T Cell Binding and Activation
Data on file 60 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 61: ShieldTx Antibody Masking Technology
61 ShieldTx Antibody masking technology for delivering on-epitope, on-tissue clinical candidates with enhanced safety and developability
Slide 62: On-Target-Off-Tissue Side Effects Limit Existing Antibodies
Diseased Tissue Healthy Tissue 62 On-Target-Off-Tissue Side Effects Severely Limit The Potential of Existing And Future Antibodies Even exquisitely specific antibodies fail in clinical trials by doing exactly what they are asked to do – hit the target. The problem often lies in the target being also
Slide 63: Engineered Epitopes Provide Integrated Solution for Masking Antibodies
63 Our Engineered Epitopes Provide an Integrated Solution for Identifying And Subsequently Masking Antibodies Diseased Tissue “On-epitope, off-tissue” therapy Healthy Tissue DME activation “On-epitope, on-tissue” therapy H+ DME: Disease Micro Environment Antibodies are activated by the removal of th
Slide 64: Masked Antibodies are a Proven Concept
64 Masked Antibodies are a Proven Concept and iBio’s Platform has the Potential to Solve Key Remaining Challenges THE PROBLEM OUR SOLUTION 1 Separate antibody and mask discovery process is inefficient Co-discovery of epitope-steered antibody and mask is more efficient Discovery process 2 Separate di
Slide 65: Anti-Trop-2 x CD3 Bi-Specific Antibody
65 Anti-Trop-2 x CD3 Bi-Specific Antibody against Tumor-Specific Trop-2 Cancer Cells
Slide 66: Trop-2 x CD3 Bi-Specific Antibody
Gilead acquired Immunomedics (Sept 2020): $21Bn Payment Trodelvy: Approval 66 Trop-2 x CD3 Bi-Specific Antibody Potentially for Head & Neck and Other Cancer Select killing cancer cells that up-regulate Trop-2 expression while improving safety margin in reducing cytokine release syndrome (CRS) • Head
Slide 67: 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 67 Trop-2 x CD3 Bi-Specific Antibody Selective Target Overexpress Trop-2 Cancer Cells Trop-2 Tumor cell Healthy
Slide 68: Trop-2 x CD3 Potently Kills Tumor Cells with Low Cytokine Release
68 iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low Cytokine Release 68 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 69: Single Dose Induces Tumor Regression in Humanized Mouse Model
69 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 70: Conditionally Activated Anti-MUC16 x CD3 Bispecific Antibodies
70 Conditionally Activated Anti -MUC16 x CD3 Bispecific Antibodies Targeting the Non -Shed MUC16 Region Leveraging iBio’s Epitope Steering, ShieldTx, and EngageTx Technologies
Slide 71: MUC16 for Ovarian and Other Cancers
+Regeneron MUC16xCD3 (Sept 2022): Ph. 1 31% ORR Ph. 2 enrollment *Regeneron, 2seventy name the target of their first solid tumor CAR-T, aim for 2023 IND ** Liu et al., An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovar
Slide 72: MUC16 Is Overexpressed and Shed by Tumor Cells
72 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 73: Immunizations Steered to a MUC16 Epitope Avoiding Shedding
Weeks 1–2 Weeks 3–4 Week 5 73 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 74: Top Three Hit Clones Bind Non-Glycosylated MUC16 Epitope
74 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 75: Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron Benchmark
75 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 76: 8G4 Clone Maintains Binding in a Fully Human Framework
76 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 77: Efficient Expression with 2x2 Format
77 Efficient Expression with 2x2 Format: Anti-CD3 x MUC16 Bispecific T-Cell Engagers scFv-Fc 2x2 Anti-MUC16 TAA Anti-CD3 (EngageTx) CD3 MUC16 TAA T Cell Tumor Cell T Cell mediated killing
Slide 78: Anti-CD3 x MUC16 T Cell Engagers Stimulate T Cells
EC50 = 14 nM EC50 = 62 nM EC50 = 19 nM EC50 = 126 nM Data on file 78 2X2 Anti-CD3 X MUC16 T Cell Engagers Stimulate T Cells in Donor PBMCs EC50 >> 100 nM EC50 >> 100 nM MUC16 Arm 1 (-)CD3 Arm only Epitope-Steered Immunized Hit StableHu Hit CD69 MFI Concentration (nM) MUC16 Arm 2 CD3 Arms MUC16 Arms
Slide 79: Anti-CD3 x MUC16 T Cell Engagers Kill OVCAR-3 Cells
EC50 = 4.0 nM EC50 = 2.5 nM EC50 = 5.2 nM EC50 = 5.2 nM Data on file 79 2X2 Anti-CD3 X MUC16 T Cell Engagers Kill OVCAR-3 Ovarian Cancer Cells EC50 >> 100 nM EC50 >> 100 nM MUC16 Arm 1 (-)CD3 Arm only Epitope-Steered Immunized Hit StableHu Hit Concentration (nM) MUC16 Arm 2 CD3 Arms MUC16 Arms % Spe
Slide 80: ShieldTx Mask Conditionally Activates MUC16 and CD3 Hits
Data on file 80 ShieldTx Engineered Epitope Mask Conditionally Activates MUC16 and CD3 Hits Mask Cleavage No Mask Mask (–MMP9) Mask (+MMP9) MMP protease Engineered Epitope Mask Intact Inactive Antibody Active Antibody Anti-MUC16 hit Anti-CD3 hit MUC16 Binding Response CD3 Binding Response time (s)
Slide 81: Anti-EGFRvIII High ADCC mAb
81 Anti-EGFRvIII High ADCC mAb Against Tumor-Specific EGFRvIII Cells
Slide 82: EGFRvIII Potentially 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 83: Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells
Skin toxicity No skin damage Data on file 83 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 bind
Slide 84: EGFRvIII-Selective mAbs Kill Tumor Cells Without Affecting Healthy Cells
Data on file 84 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
Slide 85: EGFRvIII-Specific Antibody Inhibits Tumor Growth in Xenograft Model
85 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 86: Market-Tested Potential in Immuno-Oncology
86 Market-Tested Potential in Immuno-Oncology Competitor Early-Stage Deals Signal Promising Opportunities
Slide 87: Market-Tested Potential: Immuno-Oncology Early-Stage Deals
* Acquisition / Merger + License or collaboration 87 Market-Tested Potential: Immuno-Oncology Early-Stage Deals CCR8 Coherus / Surface Oncology*: acquired for $65M JUN 2023 Pre-2020 2021 2022 2023 CCR8 Gilead / Jounce+: $85M upfront, $35M equity investment, $685M milestones SEP 2020 FEB 2021 PD-1 ag