Slides
Page 1
Breakthrough Antibodies for Obesity and Cardiometabolic Diseases Investor Call June 24, 2025
Page 2
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," "project," "plan," "intend" or similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. These forward- looking statements are based upon current estimates and includes statements regarding near term catalysts. While iBio, Inc., a Delaware corporation (including its consolidated subsidiaries, “iBio,” the “Company,” “we,” “us” or “our”) believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward- looking statements, which are based on information available to us on the date of this presentation. These forward-looking statements are subject to various risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the Company’s ability to obtain regulatory approvals for commercialization of its product candidates, or to comply with ongoing regulatory requirements, regulatory limitations relating to its ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates in the marketplace and the successful development, marketing or sale of products, its ability to attain license agreements, the continued maintenance and growth of its patent estate, its ability to establish and maintain collaborations, its ability to obtain or maintain the capital or grants necessary to fund its research and development activities, competition, its ability to retain its key employees or maintain its Nasdaq Stock Market listing, and the other factors discussed in the Company’s most recent Annual Report on Form 10-K and the Company’s subsequent filings with the SEC, including subsequent periodic reports on Forms 10-Q and 8-K. The information in this presentation is provided only as of today, and we undertake no obligation to update any forward-looking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law. Forward looking statements 2
Page 3
Revolution Sparked a New Era in Obesity Treatment Evolution Will Define Its Future Incretin Class Agonists Have Revolutionized Obesity Treatment >10% of American adults have taken a GLP-11 Weight loss previously only achievable via surgery Attention is Shifting to Therapies That Build on That Foundation Durability of weight loss Lean mass preservation and fat-specific weight loss Improved tolerability and convenience 1. https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/
Page 4
“For every 1 kg weight lost… 0.32 kg lean tissue was lost and for every 1 kg weight regained…, only 0.08 kg lean tissue was regained”1 1. Beavers et al (2011), Am J Clin Nutr. 94:767-74 2. Johnson et al (2017), J Bone Miner Res. 32(11):2278-2287, 4 The GLP-1 Revolution Unlocked Possibility — We Aim to Drive the Evolution GLP-1 Treatment start GLP-1 Treatment stop Follow up Obesity + Cardiovascular Complication Risk “Compared to (control) group, the (weight loss/regain) group had a statistically significant 39% increased risk of a frailty fracture”2 Healthy Weight
Page 5
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 (ShieldTx) Antibodies • T-cell engager panel (EngageTx) iBio’s Discovery Engine iBio’s Proprietary AI Technology Platform We use our Tech Stack to generate new IP against hard-to-drug targets – from idea to Development Candidate in 7 months • Selectively targets functional epitopes • Epitopes with complex modes of action • Unlocks novel target classes • Accelerates discovery of Ab against validated targets AI-guided precision hits that are epitope class agnostic • Gen AI creates mammalian display libraries with phage-like diversity • Single-shot multidimensional lead optimization • Compatible with multi-specific antibody formats • Antibody format agnostic Generative AI meets mammalian display: Ab optimization in 3 weeks 5
Page 6
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 6 Accelerate Success: StableHu Antibody Optimization & Mammalian Display Screening Propel Faster, Cost-Effective Antibody Development
Page 7
7 iBio’s Strategy to Redefine Obesity Care with Next-Generation Antibody Therapies Address Challenges With Current GLP-1 Drugs • Muscle mass loss • Side effects leading to discontinuation • Inconvenient dosing frequency • Room for high quality weight loss Focus on Highly Validated Targets • Preserve and build muscle mass • Fat-specific weight reduction • Targeting both sides of the equation, calorie intake and energy expenditure iBio’s Platform Fuels a High-Value Pipeline • Tackling complex, hard to drug targets • Optimizing function and developability simultaneously • Rapidly optimizing multi-specifics
Page 8
* Financing Dependent 8 iBio’s Strategy in Motion: Rapidly Advancing Next-Gen Treatments Beyond First-Gen Obesity Drugs Program Early Discovery Late Discovery Lead Optimization IND- Enabling Phase 1 IBIO-600 Myostatin IBIO-610 Activin-E Myostatin x Activin A (obesity/ potentially PH-HFpEF) Amylin Receptor Target 4 Partnered with Anticipated Milestones* IND Filing Q1 2026 PH 1 Trial Start Q2 2026 Anticipated Milestone* IND Filing 2H 2026
Page 9
Transition slide – IBIO-600 Long-Acting Anti-Myostatin Antibody
Page 10
1. Schuelke M. (2004). New England Journal of Medicine 350(2682–2688). 2. Deng, B. (2017). Nutrition and Metabolism, 14(29). 10 Strengthening the Weight Loss Journey: Myostatin Inhibition to Preserve Muscle Mass We are developing Myostatin inhibitors to preserve and increase muscle mass, complementary to current treatments Why We Target Myostatin • Incretin drugs reduce caloric intake, causing weight loss in both fat and muscle • Myostatin is a highly validated key negative regulator of muscle mass1 • Inhibition of Myostatin function drives significant muscle growth without apparent adverse health effects • Beyond its effects on muscle, Myostatin plays a role in the regulation of total body fat mass2 Binding of Myostatin to cells leads to muscle atrophy Blocking of Myostatin leads to muscle growth
Page 11
11 IBIO-600: A Differentiated Long Acting Anti-Myostatin Program Potential best-in-class PK based on allometric scaling and dosing regimen suggests 2-4x improved PK over competitors Improved Pharmacokinetics Dual myostatin and GDF11 blockade has potential for improved lean mass preservation and fat mass reductionDual Mechanism Optimized for high expression and stability to enable efficient manufacturing process Enhanced Manufacturability High formulation concentration to lower injection volumeCoformulation Optionality Administration as infrequent as twice a yearConvenience
Page 12
1. Linear elimination phase used to estimate half-life with simple linear model Data on file 12 IBIO-600 Fc Engineering Drives Extended Half-Life in Obese NHPs Dose t1/2 (days) 5 mg/kg, I.V. 52.4 IBIO-600 Fc Engineering Results in Enhanced FcRn Binding Clone Fc Fold increase over standard IgG IBIO-600 FAB Standard IgG4 1.0 IBIO-600 Engineered IgG4 16.5 IBIO-600 Demonstrates Extended Half-Life in NHPs 12 Week Pharmacokinetics Data1 0 20 40 60 80 10 100 1000 Days Serum mAb (ug/mL) IBIO-600 Study Details: • Obese, aged NHPs • Monthly DEXA scan for body composition • Periodic PK sampling Study Design: • N=3 per group • 5mg/kg single I.V. dose t1/2 = 52.4
Page 13
. 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 Data on File 13 Allometric Scaling Predicts Extended Half-Life for IBIO-600, Enabling Infrequent Dosing and Prolonged Myostatin Inhibition Y=2.49x+17 0 10 20 30 0 20 40 60 80 100 Allometric scaling YTE and LS mAb only NHP t1/2 (days) Human t1/2 (days) Dose NHP t1/2 (actual) Human t1/2 (predicted)1,2 5 mg/kg, I.V. 52.4 74-130 days Measured NHP and Predicted Human Half-Life of IBIO-600 Allometric Scaling Model for Half-Life Extended Antibodies1 Generic allometric scaling model for antibodies2 T1/2Human= T1/2NHP x Human Body Weight NHP Body Weight 0.15
Page 14
ROI (gluteal and thigh region) DEXA Data on file 14 Single Clinically Relevant Low Dose of IBIO-600 Drives Sustained Muscle Gain and Fat Loss in Aged, Obese Non-Human Primates Percent Increase in Lean Mass Weeks post dose 0 5 10 15 Change in lean mass (%, from baseline) 4 8 12 -20 -10 0 10 Change in fat mass (%, from baseline) 4 8 12 Weeks post dose Percent Decrease in Fat Mass Single 5 mg/kg Dose Single 5 mg/kg Dose
Page 15
IBIO-610 Anti-Activin E Antibody
Page 16
Type 2 Diabetes (T2D) 16 IBIO-610 Targets Activin E to Drive Targeted Fat Loss and Maintains Weight Reduction After GLP-1 Discontinuation Why We Target Activin E ▪ Activin E is a Hepatokine, produced in the liver and a member of the TGF family ▪ Activin E and its receptor are highly genetically validated ▪ Genetic loss of function decreases adiposity and risk for Diabetes / Cardiovascular Disease (CVD) ▪ 2 RNA targeting molecules provide preclinical pharmacological validation ▪ Challenge to produce active recombinant Activin E until recently has proven to be extremely difficult for antibody discovery
Page 17
Target Protein Binding Assay Reporter Cell Line Functional Assay Primary Human Adipocyte Assay Data on file 17 IBIO-610 Exhibits High-Affinity Binding and Potent Inhibition of Activin E Signaling in Engineered and Primary Human Fat Cells 0.001 0.01 0.1 1 10 100 0 2000 4000 6000 mAb (nM) RLU Isotype Cnt IBIO-610 No treatment IC50 = 158 pM 1 10 100 1000 0 10 20 30 40 IBIO-610 (nM) % pSmad2+ cells No treatment Activin E only Activin E + IBIO-610 IC50 = 44 nM
Page 18
*Non-responder outlier mice removed, IBIO-610 mouse surrogate used. 10 mg/kg, BIW dosing. DIO mice Data on file 18 IBIO-610 Induces Fat-Selective Weight Loss in Diet-Induced Obese Mice 0 7 14 21 28 -15 -10 -5 0 5 Day Body Weight % Change Baseline and Vehicle Corrected PBS IBIO-610 -8.9% *** *** *** ******* p<0.0001 p<0.005*** **** Baseline Week 4 0 5 10 15 20 Fat Mass (g) * p<0.05 * +0.4% -26% PBS IBIO-610 Weight Loss = 8.9% Fat Loss = 26% No Lean Mass Loss Baseline Week 4 0 5 10 15 20 25 Lean Mass (g) * p<0.05 +3.0% +3.5% PBS IBIO-610 Study Design Week -16 High-fat diet induction Week -7 DEXA Day 1 DEXA Day 14 DEXA Day 28 Randomization and baseline 4 weeks treatment | Semaglutide daily | Antibodies 2x week
Page 19
Data on file 19 IBIO-610 Synergizes with GLP-1 Through a Distinct, Non-Appetite-Based Mechanism Synergistic Weight Loss No Additional Appetite Suppression Visceral Fat Reduction Study Design Week -16 High-fat diet induction Week -7 DEXA Day 1 DEXA Day 14 DEXA Day 28 Randomization and baseline 4 weeks treatment | Semaglutide daily | Antibodies 2x week 0 7 14 21 28 -50 -40 -30 -20 -10 0 Day Body Weight % Change Baseline and Vehicle Corrected PBS Sema IBIO-610+Sema -27.8% -35.3% p<0.0001 vs. PBS p<0.005 vs. PBS p<0.01 vs. Sema **** *** ** ****** ************************************ ************************ **** PBS Sema IBIO-610+Sema 0 1 2 3 Food Intake (g) Average, per mouse, weeks 1-4 PBS Sema IBIO-610+Sema 0 500 1000 1500 2000 Visceral Fat (mg) Epididymal -58% -69%
Page 20
Data on file 20 IBIO-610 Prevents Weight Regain Following GLP-1 Treatment in Obese Mice Significant Prevention of Weight Regain Fat-Specific Effect Study Design 0 5 10 15 20 25 30 35 75 80 85 90 95 100 105 Day of Treatment Body Weight (%) Baseline and Vehicle Corrected PBS Sema=>PBS Sema=>IBIO-610 IBIO-610 Initiation ns *** ** * p<0.05 compared to Sema=>PBS p<0.005 compared to PBS PBS Sema => PBS Sema => IBIO-610 0 2 4 6 8 Combined Fat mWAT+iWAT+eWAT mass (g) ✱✱✱ ✱✱✱ PBS Sema => PBS Sema => IBIO-610 0.00 0.05 0.10 0.15 0.20 0.25 Quadriceps (Muscle) mass (g) PBS Sema => PBS Sema => IBIO-610 0 1 2 3 4 Liver mass (g) Vehicle Semaglutide Semaglutide 30 DIO mice PBS only Sema => PBS Sema => IBIO-610 Day 1 Sema cessation Day 14 IBIO-610 Start day 11 Day 14 Vehicle Vehicle IBIO-610 Day 15 Day 35 Necropsy (adipose, muscle, liver assessment)
Page 21
21 IBIO-610 Breaks New Ground as the Known First-in-Class Antibody Targeting Activin E Antagonist antibody offers potential for greater Activin E inhibition than siRNA-based knockdown approaches Class-Leading Pathway Targeting Pre-clinical studies demonstrate weight loss with no impact on lean massDual Mechanism Synergistic weight loss with appetite reducing drugs like GLP-1 or Amylin Synergistic to GLP-1 Receptor Agonists Stand-alone weight loss intervention and weight loss maintenance post GLP-1 or Amylin treatment Weight Lowering and Maintenance Therapy
Page 22
Transition slide – Amylin Receptor Agonist
Page 23
*Dual Amylin and Calcitonin Receptor Agonists **Selective Amylin Receptor Agonist 23 Harnessing Amylin Biology with Precision Targeting: iBio’s Engineered Antibody Agonist Approach Why We Target Amylin Selective amylin receptor agonists (rather than DACRAs*) have potential as a more precisely targeted obesity intervention • Validated metabolic hormone that promotes satiety, slows gastric emptying, and reduces postprandial glucose excursions • Clinical studies with amylin analogs confirm efficacy in weight loss, but peptide-based approaches may be sub-optimal (dosing, tolerability, manufacturability) • Amylin receptor-selective antibody agonists could provide a differentiated profile, with potential for longer duration of action and reduced side effects alone or in combination therapy Calcitonin Receptor Amylin Receptor 1 Amylin Receptor 2 Amylin Receptor 3 DACRA* 1. J Gingell, J. et al. An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology. Cell Discov 2, 16012 (2016). SARA**
Page 24
Next Generation Antibodies for Obesity Targeting Key Gaps in Current Care Corporate Highlights Lead Programs ▪ IBIO-600: Long-acting myostatin antibody ▪ IBIO-610: First-in-class Activin E antibody Pipeline Expansion ▪ 3 early-stage high novelty programs and 2 partnered programs ▪ Discovery to development candidate in as little as 7 months ▪ AI engine delivers precisely targeted antibodies with exceptional developability Near Term Catalyst 24 IBIO-600 IND/IND equivalent filing by 1Q2026* IBIO-600 Phase 1 initiated 2Q2026* IBIO-610 IND/IND equivalent filing by end of 2026* * Financing Dependent