8-K
iBio, Inc. (IBIO)
8-K
2025-01-10
For: 2025-01-10
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April 07, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (date of earliest event reported): January 10, 2025
iBio, Inc.
(Exact name of registrant as specified in charter)
Delaware
(State or other jurisdiction of incorporation)
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|---|---|
| 001-35023 | 26-2797813 |
| (Commission File Number) | (IRS Employer Identification No.) |
8800 HSC Parkway
Bryan , Texas **** 77807
(Address of principal executive offices and zip code)
( 979 ) 446-0027
(Registrant’s telephone number including area code)
N/A
(Former Name and Former Address)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of registrant under any of the following provisions:
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐ Soliciting material pursuant to Rule 14a-12(b) under the Exchange Act (17 CFR 240.14a-12)
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
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|---|---|---|
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered |
| Common Stock, $0.001 par value per share | IBIO | NYSE American |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by checkmark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 7.01. Regulation FD Disclosure.
iBio, Inc. (the “Company”) has updated its corporate presentation. A copy of the updated corporate presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 and in the corporate presentation attached as Exhibit 99.1 to this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01 and in the corporate presentation attached as Exhibit 99.1 to this Current Report on Form 8-K shall not be incorporated by reference into any filing with the Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
The corporate presentation attached as Exhibit 99.1 to this Current Report on Form 8-K includes “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained therein are “forward-looking” rather than historical.
The Company undertakes no duty or obligation to update or revise the information contained in this Current Report on Form 8-K, although it may do so from time to time if its management believes it is appropriate. Any such updating may be made through the filing of other reports or documents with the Securities and Exchange Commission, through press releases or through other public disclosures.
Item 8.01. Other Events.
The Company has updated its corporate presentation, a copy of which is attached as Exhibit 99.1 to this Current Report on Form 8-K, for use in meetings with investors, analysts and others. The information on slides 8, 14, 15, 19, 21, 22, 23 and 25 of Exhibit 99.1 is incorporated by reference herein.
The Company, in collaboration with AstralBio Inc., has developed an antibody that inhibits the function of Activin E, a promising therapeutic target for cardiometabolic disorders and obesity using the Company’s patented Machine-Learning Antibody Engine. Using its advanced epitope engineering technology, the Company created antibodies targeting all five epitopes on the Activin E protein without producing Activin E itself.
Data collected from preclinical studies conducted by the Company show strong antibody binding to Activin E and the ability to block its signaling. The compound discovered by the Company demonstrates exceptional potency, with binding experiments indicating sub-nanomolar kinetics. In multiple cell-based assays, including studies on human adipocytes, the antibody has achieved complete blockade of Activin E-mediated signaling. Activin E plays a significant role in regulating energy homeostasis in adipose tissue and overall metabolic health.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
The following exhibits are furnished with this Current Report on Form 8-K:
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|---|---|---|
| Exhibit No. | Description | |
| 99.1 | | Corporate Presentation of iBio, Inc., dated January 2025 |
| 104 | | Cover Page Interactive Data File (the cover page XBRL tags are embedded within the inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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| IBIO, INC. | |||
| Date: January 10, 2025 | By: | /s/ Marc A. Banjak | |
| Name: | Marc A. Banjak | ||
| | | Title: | Chief Legal Officer |
Exhibit 99.1
| Breakthrough Antibodies<br>for Obesity and<br>Cardiometabolic Diseases<br>Enabled by an AI-Platform Scalable<br>for Future High-Value Indications<br>Corporate Presentation<br>January 2025 |
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| Certain statements in this presentation constitute "forward<br>-looking statements" within the<br>meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as<br>"may," "might," "will," "should," "believe," "expect," "anticipate," "estimate," "continue,"<br>"predict," "forecast," "project," "plan," "intend" or similar expressions, or statements regarding<br>intent, belief, or current expectations, are forward<br>-looking statements. These forward<br>-<br>looking statements are based upon current estimates and includes statements regarding<br>near term catalysts. While iBio, Inc., a Delaware corporation (including its consolidated<br>subsidiaries, “iBio,” the “Company,” “we,” “us” or “our”) believes these forward<br>-looking<br>statements are reasonable, undue reliance should not be placed on any such forward<br>-<br>looking statements, which are based on information available to us on the date of this<br>presentation. These forward<br>-looking statements are subject to various risks and<br>uncertainties, many of which are difficult to predict that could cause actual results to differ<br>materially from current expectations and assumptions from those set forth or implied by any<br>forward<br>-looking statements. Important factors that could cause actual results to differ<br>materially from current expectations include, among others, the Company’s ability to<br>obtain regulatory approvals for commercialization of its product candidates, or to comply<br>with ongoing regulatory requirements, regulatory limitations relating to its ability to promote<br>or commercialize its product candidates for specific indications, acceptance of its product<br>candidates in the marketplace and the successful development, marketing or sale of<br>products, its ability to attain license agreements, the continued maintenance and growth<br>of its patent estate, its ability to establish and maintain collaborations, its ability to obtain or<br>maintain the capital or grants necessary to fund its research and development activities,<br>competition, its ability to retain its key employees or maintain its NYSE American listing, and<br>the other factors discussed in the Company’s most recent Annual Report on Form 10-K and<br>the Company’s subsequent filings with the SEC, including subsequent periodic reports on<br>Forms 10-Q and 8-K. The information in this presentation is provided only as of today, and<br>we undertake no obligation to update any forward<br>-looking statements contained in this<br>presentation on account of new information, future events, or otherwise, except as<br>required by law.<br>Forward looking statements<br>2 |
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| 3<br>An Antibody (Ab) Discovery Platform for Cardiometabolic Disease and Beyond<br>Advancing Antibodies Against Difficult Targets With an Integrated and Validated AI Technology Stack<br>Apply<br>2026<br>Obesity programs<br>advance into<br>clinic<br>Scale<br>2029<br>Obesity programs advance<br>to late clinical development<br>Assets in other disease areas<br>enter clinical development<br>Acquire<br>2022<br>Acquisition of AI-enabled Ab discovery<br>pioneer RubrYc<br>Therapeutics®<br>Validate<br>2024<br>AI Technology platform<br>validated in<br>cardiometabolic<br>disease |
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| iBio's AI-Driven<br>Antibody Discovery<br>Platform Has<br>Delivered<br>Corporate Highlights<br>• AI-driven antibody discovery<br>Platform including patented<br>Epitope steering, StableHu ,<br>EngageTx , and ShieldTx®<br>• Platform has delivered<br>Development Candidates in as<br>little as 7 months<br>• 11 active programs:<br>5 Cardiometabolic/Obesity<br>programs - 3 of which are<br>partnered - demonstrating the<br>value of our approach<br>6 in-house pre-clinical programs in<br>immuno-oncology<br>Near Term Catalyst<br>2025<br>• Long-acting anti-Myostatin<br>program; IND by Q4 ‘25/Q1‘26<br>2026<br>• Ph 1 trial for long-acting anti-Myostatin program initiated by<br>2H ‘26<br>• Additional IND by 2H ‘26<br>4 |
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| Any Epitope on Any Drug Target<br>AI Epitope Engineering and Antibody Optimization Engines unlock challenging target classes<br>• Multi-layer technology<br>platform addresses multiple<br>challenges in Ab discovery<br>• Patented Epitope Steering<br>technology<br>• Single-step Ab StableHu x<br>Mammalian Display<br>• Masked (ShieldTx) Antibodies<br>• T-cell engager panel<br>(EngageTx)<br>iBio’s Discovery Engine<br>iBio’s Proprietary AI<br>Technology Platform<br>We use our Tech Stack to generate new IP against hard-to-drug targets –<br>from idea to Development Candidate in 7 months<br>• Selectively targets functional<br>epitopes<br>• Epitopes with complex modes of<br>action<br>• Unlocks novel target classes<br>• Accelerates discovery of Ab<br>against validated targets<br>AI-guided precision hits that<br>are epitope class agnostic<br>• Gen AI creates mammalian display<br>libraries with phage-like diversity<br>• Single-shot multidimensional lead<br>optimization<br>• Compatible with multi-specific antibody<br>formats<br>• Antibody format agnostic<br>Generative AI meets mammalian<br>display: Ab optimization in 3 weeks<br>5 |
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| 6<br>iBio’s AI Tech Stack is a Fully Integrated Solution for Antibody Discovery<br>Enables and accelerates Antibody Discovery & Development Against Hard-to-Drug Targets |
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| Transition slide –<br>Harnessing the Power of<br>Our Platform to Address<br>Challenges in Cardio-metabolic Disease |
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| 8<br>iBio’s Rapidly Advancing High Value Obesity and Cardiometabolic Pipeline<br>Therapeutic<br>Area<br>Program Early<br>Discovery<br>Late<br>Discovery<br>Lead<br>Optimization<br>IND-Enabling<br>Cardio-metabolic<br>IBIO-600<br>Myostatin<br>(obesity)<br>Myostatin x Activin A<br>(obesity/ potentially PH-HFpEF)<br>Activin E<br>(obesity)<br>Target 3<br>(obesity)<br>Target 4<br>(obesity)<br>Partnered with |
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| 9<br>Current Treatments in Obesity Fall Short<br>Significant Unmet Medical Need for Innovation to Improve Overall Metabolic Health and Function<br>The Next<br>Generation<br>Potential Avenues:<br>• Preservation of muscle mass during GLP-1 agonist induced weight loss<br>• Improved fat burning and prevention of dyslipidemia<br>• Improved cardiac function and treatment of cardiovascular disease related to metabolic syndrome<br>iBio’s AI-enabled platform is addressing the challenges of current anti-obesity medicines |
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| 10<br>A Clear Strategy to Create a High-Value Pipeline of Differentiated Products<br>A prime opportunity exists for GLP-1 complementary therapeutic approaches<br>• Muscle mass loss<br>• Side effects leading to<br>discontinuation<br>• Inconvenient dosing frequency<br>• Room for high quality weight<br>loss<br>Address Challenges With<br>Current GLP-1 Drugs<br>• Preserve and build muscle<br>mass<br>• Fat-specific weight reduction<br>• Targeting both sides of the<br>equation, calorie intake and<br>energy expenditure<br>Focus on Highly<br>Validated Targets<br>• Tackling complex, hard to drug<br>targets<br>• Optimizing function and<br>developability simultaneously<br>• Rapidly optimizing multi-specifics<br>iBio’s Platform Fuels a<br>High-Value Pipeline |
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| Transition slide –<br>IBIO-600<br>Long-Acting Anti-Myostatin<br>Antibody |
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| 1. Schuelke M. (2004). New England Journal of Medicine 350(2682–2688).<br>2. Deng, B. (2017). Nutrition and Metabolism, 14(29). 12<br>Myostatin Antagonism<br>Enhancing the Quality of Weight Loss by Maintaining Muscle Mass During and After Weight Loss with GLP-1s<br>We are developing Myostatin inhibitors to preserve and increase muscle mass, complementary to treatment<br>with GLP-1 drugs<br>Why We Target Myostatin<br>• Incretin drugs reduce caloric intake,<br>causing weight loss in both fat and muscle<br>• Myostatin is a highly validated key<br>negative regulator of muscle mass1<br>• Inhibition of Myostatin function drives<br>significant muscle growth without<br>apparent adverse health effects<br>• Beyond its effects on muscle, Myostatin<br>plays a role in the regulation of total body<br>fat mass2<br>Binding of<br>Myostatin to cells<br>leads to muscle<br>atrophy<br>Blocking of<br>Myostatin leads to<br>muscle growth |
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| 1. Data available on request<br>IBIO-600: A Long-Acting First-in-Class Anti-Myostatin Antibody<br>First Anti-Myostatin Antibody With a Target Product Profile Specifically Tailored for an Obese Patient Population<br>IBIO-600<br>Long-Acting Anti-Myostatin Antibody<br>First-in-class innovation: First Myostatin therapy tailored for large, chronic disease<br>populations<br>Convenient Dosing: Half-life extension anticipated to support dosing every 2-3 months<br>Broad Potential: Opportunities for expansion into sarcopenia, frailty, and other age-related disorders<br>Highly Developable: Resistant to various stress conditions, improved expression, high<br>thermostability1<br>• Well-tolerated for long-term use<br>• Infrequent subcutaneous self-administration<br>Target product profile<br>characteristics for<br>obese patients<br>• Rapidly generates novel IP<br>• Large library of novel lead<br>molecules<br>AI-enabled CDR design<br>• Optimized for affinity, half-life and<br>manufacturability<br>Single-shot multi-dimensional<br>lead optimization<br>13 |
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| 14<br>IBIO-600 Increases Muscle Differentiation in Primary Human Myoblast Cells<br>Red indicates muscle cell growth and development (as measured by myoblast differentiation)<br><br>Myostatin Only<br>Myostatin + IBIO-600<br>IBIO-600 potently increases<br>myoblast differentiation<br>Baseline human myoblast<br>differentiation (untreated)<br>Myostatin inhibits human<br>myoblast differentiation<br>IBIO-600 blocks Myostatin<br>and increases human<br>myoblast differentiation<br>The human Myoblast differentiation model is highly predictive of muscle growth in humans |
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| Body weight loss up to day 14<br>In this study the murine surrogate antibody of IBIO-600 was used 15<br>Interim Data: IBIO-600 Preserves Muscle Mass in GLP-1 Treated Diet Induced<br>Obesity Mice<br>Day 14 Interim<br>Data Collection<br>Day -7 Day 1 Day 28 Day 56<br>Body composition<br>Insulin tolerance test<br>Grip Strength<br>Study Design<br>Interim Data<br>Lean mass change<br>on Day 14<br>Sema + 10<br>mg/kg IBIO-600 |
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| Transition slide –<br>Anti-Myostatin x Activin A<br>Bispecific Antibody |
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| 17<br>Combined Myostatin and Activin A Antagonism<br>Synergistic Effect on Muscle Growth and Potential Treatment for Pulmonary Hypertension (PH) in Heart Failure With Preserved Ejection Fraction (HFpEF)<br>For obesity, we are developing bi-specific co-inhibitors of Myostatin and Activin A to enhance muscle growth<br>and improve quality of weight loss during and after treatment with incretin drugs<br>Why Myostatin & Activin A<br>• Myostatin and Activin A are key negative<br>regulators of muscle mass<br>• Both are members of the TGFβ superfamily<br>• Activin A mechanism is pharmacologically<br>validated1, 2<br>• Combined Activin A and Myostatin inhibition,<br>causes more pronounced muscle growth3<br>• Myostatin and Activin A inhibition are key<br>features for treating PH-HFpEF<br>1.Villanueva, J. et al. Am J Cardiovasc Drugs (2024).<br>2.US20220119514A1, Regeneron corporate slides<br>3.Latres, E. et al. Nat Commun 8, 15153 (2017).<br>Binding of<br>Myostatin and<br>Activin A to cells<br>leads to muscle<br>atrophy<br>Simultaneous<br>blocking of<br>Myostatin and<br>Activin A leads to<br>muscle growth |
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| • Well-tolerated for long-term use<br>• Infrequent subcutaneous self-administration<br>*Bone Morphogenetic Proteins<br>A Long-Acting First-in-Class Anti-Myostatin x Activin A Bispecific Antibody<br>Myostatin x Activin A<br>Bi-specific<br>Target product profile for obese<br>and potentially Ph-HFpEF patients<br>First-in-class innovation: Myostatin x Activin A bispecific antibody with unique<br>therapeutic potential<br>Convenient Dosing: Half-life extension potentially enables dosing every 2-3 months<br>Optimize Potency: Higher-valency antibody format might increase potency and<br>reduce dose<br>Potential Advantage: May avoid BMP* inhibition, minimizing bleeding risks<br>associated with ligand traps<br>• Generates novel IP<br>• Large library of novel lead<br>molecules<br>AI-enabled CDR design<br>• Bi-specific optimized for affinity,<br>half-life and manufacturability<br>Single-shot multi-dimensional<br>lead optimization<br>18 |
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| 19<br>iBio’s Myostatin and Activin A Bi-Specific Targets Both Key Negative Muscle<br>Regulators, Synergistically Increasing Muscle Mass<br>Increased muscle fusion index in human muscle stem cells is a<br>surrogate of muscle growth<br>Negative control (Myostatin + Activin A) without antibody<br>Myostatin + Activin A with Activin A Antibody<br>Myostatin + Activin A with Myostatin Antibody<br>Myostatin + Activin A with Myostatin x Activin A Bi-Specific<br>Only a Myostatin x Activin A<br>bi-specific antibody fully<br>blocks both muscle growth<br>suppressors, enabling optimal<br>growth, while single-target<br>antibodies fall short<br>In Vitro Data |
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| Anti-Activin E<br>Antibody |
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| Type 2 Diabetes (T2D) 21<br>Activin E Antagonism<br>Attractive Fat-Specific Weight Loss Mechanism with Excellent Compatibility for Bi-Specific Pairing with Anti-Myostatin<br>We are developing inhibitors of Activin E to promote fat-specific weight loss, either as a standalone<br>drug or as a bi-specific antibody with Myostatin.<br>Why We Target Activin E<br>• Activin E is a Hepatokine, produced in the liver and<br>a member of the TGFβ family<br>• Activin E and its receptor are highly genetically<br>validated<br>• Genetic loss of function decreases adiposity and risk<br>for Diabetes / Cardiovascular Disease (CVD)<br>• 2 RNA targeting molecules provide preclinical<br>pharmacological validation<br>• Challenge to produce active recombinant Activin E<br>until recently has proven to be extremely difficult for<br>antibody discovery |
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| • First-in-class functional<br>antibody for Activin E<br>iBio’s AI-Enabled Epitope Steering Engine Bypasses Recombinant Activin E,<br>Creating Functional Antibodies Directly from the Target Sequence<br>Activin E<br>Antibody<br>AI epitope engineering<br>breaks barrier to discovery<br>Innovative AI solution: Epitope steering engine overcame the challenge of full-length<br>Activin E unavailability, creating a first-in-class antibody targeting Activin E<br>Convenient Dosing: Half-life extension potentially enables dosing every 2-3 months<br>Versatile Combinability: Easily integrates with other TGFβ family targets into bi-specific<br>antibodies, offering a potential alternative to incretin drugs (fat-specific weight loss with<br>increase in muscle mass)<br>• Rapidly generates novel IP<br>• Large library of novel lead<br>molecules<br>AI-enabled CDR design<br>• Optimized for affinity, half-life and<br>manufacturability<br>Single-shot multi-dimensional<br>lead optimization<br>22 |
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| 23<br>iBio’s AI Engineered Epitope Engine Delivers a First-in-Class Functional<br>Activin E Antibody<br>Challenge<br>We have uniquely solved an industry-wide problem with our proprietary epitope engineering engine<br>to create functional Activin E antibodies<br>iBio’s Solution Breakthrough Activin E Signaling (lower is better)<br>Antibody Concentration (nM)<br>Active, native recombinant<br>Activin E unavailable until<br>recently<br>First-in-Class Activin E Antibody Blocks<br>Activin E Signaling<br>Create Engineered Epitopes to<br>guide Antibodies against full-length Activin E |
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| Immuno-Oncology |
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| *Tumor Micro Environment 25<br>Beyond Cardiometabolic – Driving Value Within Our Oncology Pipeline<br>Program MoA Potential<br>Indications<br>Early<br>Discovery<br>Late<br>Discovery<br>Lead<br>Optimization<br>IND-Enabling<br>Highlights<br>IBIO-101 Treg depletion,<br>IL-2 sparing<br>Solid tumors,<br>orphan<br>indications<br>Synergistic efficacy with<br>checkpoint inhibitors<br>CCR8<br>Tumor-infiltrating Treg<br>depletion<br>Solid tumors Highly selective vs. closely<br>related GPCRs<br>Trop-2 x CD3<br>Tumor-protease<br>activated T<br>cell engager<br>Solid tumors<br>ShieldTx technology enables<br>masking; delivery as pro-drug<br>activated in TME*<br>MUC16 x CD3<br>Tumor-protease<br>activated T<br>cell engager<br>Ovarian and<br>pancreatic<br>cancer<br>Binds membrane-proximal<br>epitope, distinct from<br>Regeneron MUC16xCD3<br>EGFRvIII ADCC-enhanced Fc Glioblastoma Highly selective for EGFRvIII<br>over EGFR<br>Target 5<br>Protein<br>Complex<br>Stabilization<br>Solid tumors<br>Innovative mechanism of<br>action locking protein complex<br>in inactive form<br>ShieldTx<br>EngageTx<br>ShieldTx<br>EngageTx |
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| 26<br>A Leadership Team with Deep Industry Experience<br>Deep expertise in cardiometabolic<br>disorders<br>Marc Banjak<br>CLO<br>Martin Brenner, DVM, Ph.D.<br>CEO & CSO<br>Kristi Sarno<br>Senior VP BD<br>Felipe Duran<br>CFO |
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| Executive Summary Corporate Highlights<br>• Patented AI-driven Discovery<br>Tech Stack which can:<br>• Rapidly advance a highly<br>developable pre-clinical<br>pipeline<br>• Solve hard-to-drug problems<br>• Pipeline of cardio/obesity<br>rapidly progressing<br>• Pipeline of immuno-oncology molecules ready<br>for strategic partners<br>Financial Highlights<br>• $11.3M in Cash and<br>Restricted cash as of<br>September 30, 2024<br>• Cash runway into Q1<br>FY26<br>• 9.1M shares outstanding<br>as of November 21, 2024<br>27 |
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| Appendix |
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| 29<br>Technology<br>Platform &<br>Preclinical<br>Pipeline |
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| 30<br>Technology<br>Stack |
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| 31<br>iBio’s Tech Stack Aims to Solve Major Challenges in Antibody Discovery &<br>Development<br>Epitope<br>Steering<br>StableHu &<br>Mammalian Display<br>Unlocking Novel<br>Biology<br>Reduced Lead-Optimization Time<br>Optimization in less than 4 weeks<br>Minimized Developability Risk<br>Mammalian Display in<br>Manufacturing Cell Line<br>Potential for Improved Safety<br>Selective “on-tissue” action of<br>masked antibodies<br>First in Class Antibodies and / or<br>Best in Class Antibodies<br>Pursuit of Elusive<br>Targets<br>GPCRs, Ion Channels,<br>Protein Complexes<br>Complex modalities<br>Agonistic Antibodies,<br>Cell Activators,<br>Protein Complex<br>Stabilizers<br>Fully human Ab<br>Reduced immunogenicity<br>risk by clinically validated<br>Ab frameworks<br>Speed<br>Rapid hit ID vs immunization<br>campaigns<br>Improved Developability<br>Known sequence liabilities<br>eliminated<br>Optimized<br>Antibody Leads<br>Proprietary Naïve<br>mAb Library<br>Library Diversity<br>ML tools create focused<br>diversity with smaller library<br>size<br>Speed<br>Simultaneous, Multi-Dimensional Optimization<br>Improved Developability<br>Mammalian Display with<br>production cell lines<br>exclusively yields expressible<br>clones<br>Improved Speed and Developability |
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| 32<br>iBio’s Tech Stack Addresses Immuno-oncology Discovery and<br>Development Challenges<br>ShieldTx<br>2nd Gen T-cell<br>Engager Panel<br>Finely tuned T-cell engagement<br>Adjustable T-cell engagement to fit<br>any tumor target engager<br>Improved safety prediction<br>Cyno cross reactivity allows for<br>better preclinical safety<br>assessment<br>Improved Safety Profile<br>Tissue selective action through<br>“smart”, conditionally activated,<br>antibodies<br>Sequence Diversity<br>Increased humanness and broad<br>CD3 activity for optimized pairing<br>with antigen arms<br>Hu-Cyno Cross Reactivity<br>Risk reduction via cyno monkey<br>toxicity study compatibility<br>Range of Cytokine Release<br>Tailored cytokine release for<br>expanded therapeutic window<br>Enhanced Efficacy<br>and Safety of I/O<br>Antibody Leads<br>EngageTx<br>Greater Safety With<br>Tissue Specificity<br>Seamlessly Integrated Ab<br>Masking<br>Engineered epitopes serve<br>dual purpose for raising and<br>masking of Abs<br>Flexibility in Candidate<br>Selection<br>Simultaneous co-optimization<br>of Ab, mask and linker<br>provides maximized flexibility<br>in candidate selection |
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| Match<br>Engineered<br>Structure to<br>Target<br>Refined for<br>Greater<br>Stability<br>Optimized for<br>Water<br>Solubility<br>33<br>Unlocking High-Value Drug Targets: AI-Engineered Epitopes are Generalizable<br>to a Broad Set of Complex Structural Drug Binding Sites<br>Junctional<br>Epitopes<br>Complex<br>Secondary<br>Structures<br>Membrane<br>Proteins<br>(e.g. GPCR)<br>Loop<br>Display 1<br>2<br>3<br>AI Epitope<br>Engine |
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| Input<br>Antibody<br>StableHu<br>AI-Engine<br>Mammalian<br>Display<br>Output<br>Antibody<br>Template<br>CDR<br>Predict library of<br>human CDR variants<br>Single-cell screen<br>mammalian display CDR<br>library<br>Optimized antibody<br>with fully human CDRs<br>34<br>Accelerate Success: StableHu Antibody Optimization & Mammalian Display<br>Screening Propel Faster, Cost-Effective Antibody Development |
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| 35<br>“Smart” Antibodies: ShieldTx Conditionally Activated Antibodies Strive to<br>Improve Safety by Selectively Targeting Diseased but not Healthy Tissue<br>H+<br>Diseased Tissue<br>“On-epitope,<br>off-tissue”<br>therapy<br>Healthy Tissue<br>“On-epitope,<br>on-tissue”<br>therapy<br>DME<br>activation<br>Diseased Tissue<br>“On epitope,<br>on tissue”<br>therapy<br>Healthy Tissue<br>“On epitope,<br>off tissue”<br>therapy |
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| 36<br>EngageTx, a CD3-Based T-Cell Engager Panel, Addresses 3 Key Challenges:<br>Cytokine Release, NHP Cross-Reactivity and Immunogenicity Risk<br>Numerous<br>tumor<br>antigen arms<br>Diverse<br>CD3<br>engager arms<br>1 Sequence Diversity 2 Hu-Cyno Cross-Reactivity 3 Range of Cytokine Release<br>Increased humanness and broad CD3<br>activity for optimized<br>paring with tumor antigen arms<br>Risk reduction via cyno monkey<br>toxicity study compatibility<br>Tailored cytokine release for expanded<br>therapeutic window<br>Release of<br>cytokines<br>TNFα, IFNγ,<br>IL-2, (IL6)<br>Increased<br>cytotoxicity<br>Reduced<br>cytokine<br>release<br>Release of<br>cytotoxic granules<br>Granzyme,<br>Perforin<br>Cascade of<br>immune activation<br>Tumor<br>cell<br>death<br>Activated<br>T cell<br>Tumor cell |
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| Epitope<br>Engineering<br>Engine*<br>Proprietary<br>Antibody<br>Library<br>AI-powered mammalian-display<br>co-optimization of mono/multi-specific antibody and<br>conditionally activated mask<br>Engineered<br>Epitope<br>Steering<br>AI-powered<br>engineering of<br>conformational<br>epitopes<br>Epitope-specific<br>antigens that steer<br>discovery to<br>intended epitopes<br>1 2 3 4<br>Naïve human<br>sequence<br>antibody library,<br>free of liabilities<br>Optimized<br>Antibody<br>Leads<br>5<br>Evaluated &<br>ranked in<br>translational<br>disease models<br>* U.S. Patent No. 11,545,238 (issued January 3, 2023) 37<br>iBio's Platform Tackles Discovery Challenges for the Next Era of Antibodies<br>EngageTx ShieldTx<br>StableHu Antibody<br>Optimizer<br>On-epitope,<br>On-tissue<br>Clinical Candidate |
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| 38<br>IBIO-101<br>IL-2 Sparing Anti-CD25 |
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| Recent Transactions & Milestones<br>*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<br>releases<br>**Data presented by Roche at AACR 2023<br>39<br>IBIO-101 for Regulatory T-Cell (Treg) Depletion<br>Depletion of<br>immunosuppressive Tregs<br>via antibody<br>dependent cellular<br>cytotoxicity (ADCC),<br>without disrupting<br>activation of effector<br>T-cells (Teffs) in the tumor<br>microenvironment<br>• Solid tumors<br>• Hairy cell leukemia<br>• Relapsed mult. myeloma<br>• Lymphoma<br>• Head & neck cancer<br>*<br>Roche / Tusk Therapeutics (Sep 2018)<br>$81M upfront,<br>$677M milestones<br>• IL-2 sparing anti-CD25 antibodies<br>enables depletion of Tregs without<br>affecting Teffs<br>• Fast-follower to Roche’s RG6292<br>clinical molecule<br>Target Mechanism Potential Indications Differentiation / Opportunity<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>**Roche RG6292 Ph1 Data (Apr 2023)<br>Well-tolerated: manageable safety profile<br>Confirmed MOA: Reduced intratumoral Tregs<br>Efficacy: 29% stable disease (45% PD-L1 combo) |
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| Data on file. Treg = Regulatory T Cells; Teff = Effector T Cells; ADCC = Antibody Dependent Cellular Cytotoxicity 40<br>IBIO-101 Reduces Tumor Growth in Preclinical Studies by Selectively Depleting<br>Immunosuppressive Tregs without Affecting Cancer Killing Teffs<br>Indiscriminate<br>depletion of<br>Treg + Teff<br>TUMOR<br>Teff<br>1st gen CD25 mAbs<br>depleted immuno-suppressive Treg and<br>immuno-stimulatory Teff<br>Limited efficacy<br>2nd gen IBIO-101<br>selectively targets Tregs<br>without blocking IL-2<br>signaling to Teffs<br>Strong preclinical<br>anti-tumor response<br>IBIO-101<br>Proliferation<br>Natural<br>Killer Cell<br>Preferential Treg<br>depletion<br>ADCC<br>1st Gen CD25<br>TUMOR<br>IL-2<br>CD25<br>(IL-2Rα)<br>JAK JAK<br>Treg<br>JAK JAK<br>Teff<br>JAK JAK<br>Treg<br>JAK JAK<br>Teff<br>IL-2 signaling<br>Blocked IL-2 pathways<br>IL-2 |
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| RG6292 is Roche’s monoclonal antibody that targets CD25 (IL-2Rα).<br>IBIO-101 data on file.<br>41<br>IBIO-101 Selectively Depletes Tregs<br>while preserving<br>IL-2 signaling<br>IBIO-101 potently binds<br>recombinant CD25<br>which leads to Treg<br>depletion<br>while sparing Teffs |
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| 1hCD25 animal model - Data on file. 42<br>IBIO-101 Increases in Teff/Treg Ratio in Preclinical Studies<br>Inhibiting Tumor Growth<br>Tumor growth inhibition<br>correlates with T-eff/T-reg ratio<br>Potently increases T-eff/T-reg<br>ratio1<br>* Significant vs * Significant vs Negative Control<br>hIgG1 Isotype |
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| *hCD25 animal model - Data on file. 43<br>IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy<br>IBIO-101 + PD-1 Checkpoint Inhibitor In PreClinical<br>Studies Enhances Tumor Suppression<br>* Significant vs Negative Control<br># Significant vs Anti-PD-1 |
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| 44<br>IBIO-101 is an Antibody With Favorable Characteristics for CMC Development<br>• Identified manufacturing partner to produce IBIO-101 for Phase 1&2 clinical trials<br>• Discovered suitable cell lines for manufacturing MCB<br>• Established IBIO-101 CMC methodology for producing high yield, high purity, stable product<br>under cGMP conditions<br>Potential for Master Cell Bank (MCB)<br>Development From 8 Promising Cell Lines Unoptimized Cell Lines Already Show<br>Promising IBIO-101 Yields |
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| 45<br>Anti-CCR8<br>High ADCC Anti<br>-CCR8<br>for the Depletion of<br>T-regulatory Cells |
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| *Fibrogen / HiFiBio: Fibrogen purchased option to multiple programs in June 2021, then exercised the option for excl. license to CCR8 program in Dec. 2021.<br>**Gilead / Jounce: Exclusive worldwide license to anti-CCR8 antibody.<br>*** Coherus / Surface Oncology: acquisition, announced in June 2023, adds two clinical assets, including a phase 2 anti-IL-27 and a phase 1/2 anti-CCR8 for oncology.<br>46<br>CCR8 for Tumor-Infiltrating Treg Depletion<br>Tumor-infiltrating Tregs<br>highly express CCR8.<br>iBio program targets<br>depletion of highly<br>immunosuppressive<br>CCR8+ Tregs in tumor<br>microenvironment via<br>an ADCC mechanism.<br>• Broadly applicable in solid<br>tumors<br>• Prospective combination<br>therapy<br>Target Mechanism Potential Indications Differentiation / Opportunity<br>Recent Transactions & Milestones<br>• Selective binding to CCR8<br>over its close homolog, CCR4<br>**Gilead / Jounce (Dec 2022):<br>Original deal: $85M upfront, $35M<br>equity investment, $685M milestones.<br>2023 Buyout: $67M for remaining rights.<br>*<br>Fibrogen / HiFiBio<br>(Jun & Dec 2021):<br>$25M option fee, $35M option<br>exercise, $1.1B milestones<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>***Coherus / Surface<br>(Jun 2023):<br>Acquired for $65M |
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| 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 47<br>CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive<br>Depletion of CCR8+ Treg cells has potential to evoke potent tumor immunity<br>• Systemic inflammation<br>• Skin toxicity<br>• Platelet<br>depletion/aggregation<br>Intratumor cytotoxic T-cell<br>activation & tumor death<br>Adverse events<br>iBio CCR8<br>specific antibody<br>CCR8 & CCR4<br>nonspecific antibody<br>CCR4+ cells killed<br>CCR4+ cells spared |
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| Data on file 48<br>Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1 Antagonism<br>and CCR8-Specific Cell Killing<br>High Specificity CCR8 Cell Binding<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>2<br>4<br>6<br>8<br>10<br>hCCR8 overexpressed cells<br>Ab. (nM)<br>MFI<br>hIgG1 isotype<br>mIgG2A isotype<br>Anti -hCCR4 - EC50 = NA<br>Anti-mCCR8 - EC50 = NA<br>SD-356253 - (iBio) - EC50 = 0.78 nM<br>SD-692676 - (GS-1811) - EC50 = 0.43 nM<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>10<br>20<br>30<br>40<br>50<br>hCCR4 overexpressed cells<br>Ab. (nM)<br>MFI<br>hIgG1 isotype<br>mIgG2A isotype<br>Anti -hCCR4 - EC50 = 42.5 nM<br>Anti-mCCR8 - EC50 = NA<br>SD-356253 - (iBio)- EC50 = NA<br>SD-692676 - (GS-1811)- EC50 = NA<br>0.000001<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>0<br>10<br>20<br>30<br>40<br>CCR8 overexpressed cell<br>Ab. (nM)<br>% of cell killing<br>hIgG1<br>hCCR4 - EC50 =NA<br>SD-356253-(iBio) - EC50 = 0.004 nM<br>SD-692676-(GS-1811) - EC50 = 0.002 nM<br>PBMC-Induced CCR8 Cell Killing<br>Potent binding to CCR8 overexpressing cells<br>No binding to CCR4 overexpressing cells<br>(Jounce/Gilead)<br>(Jounce/Gilead)<br>(Jounce/Gilead)<br>Untreated<br>CCL1 (7 nM)<br>CCL1 (7 nM) + hIgG1 Iso. Ctl.<br>Anti-hCCR8 (+)Ctl.<br>SD-6926776-(GS-1811) Jounce/Gilead<br>SD-356253 (iBio)<br>CCR8-CCL1 Antagonism |
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| 49<br>iBio’s CCR8-Specific High ADCC Antibody Induces Tumor Regression in a<br>Transgenic Human CCR8 Mouse Model<br>Day -7 Day 0 Day 0, 3, 7, 10<br>Tumor<br>implantation<br>Subsequent<br>dosing<br>Test article<br>dosing (i.p)<br>0 2 4 6 8 10 12 14<br>0<br>50<br>100<br>150<br>200<br>250<br>300<br>Days after treatment<br>Tumor Volume (mm3<br>)<br><br><br><br>*<br>*<br>*<br>* p<0.05 vs negative control<br>*<br>*<br>+22% Tumor<br>regression<br>+10% Tumor<br> regression<br>100 % Tumor<br>Inhibition<br><br>hIgG1 negative control (10 mg/kg)<br>Competitor in clinic (10 mg/kg)<br>SD-171467-afuc (10 mg/kg) |
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| 50<br>Unlocking the Power of<br>Bi-Specific Antibodies<br>with EngageTx, Our Versatile<br>CD3 mAb Panel<br>Wide Range of Affinities, NHP Cross<br>Reactivity, High Developability |
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| *Eli Lilly / Merus: Fibrogen Research collaboration using Merus’ proprietary platform to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies.<br>** GSK WuXi: License of WuXi’s preclinical CD3 bi-specific, plus 3 earlier stage programs<br>***Amgen / Teneobio: Teneobio was developing a heavy-chain only platform as well as its CD3 engager technology. TNB-585, the lead program, was in phase 1.<br>+ Gilead / MacroGenics: Gilead granted option to MGD024, a phase 1 CD3 bi-specific, plus collaboration on two additional research programs.<br>51<br>Next Generation Anti-CD3 T Cell Engagers<br>T-cell-redirecting<br>bispecific antibodies are<br>a new therapeutic class<br>that simultaneously<br>targets CD3 on T cells<br>and tumor antigens,<br>inducing T cell mediated<br>tumor cell killing<br>• Broad solid tumor potential<br>• Expands therapeutic options<br>across programs<br>Target Mechanism Potential Indications Differentiation / Opportunity<br>Recent Transactions & Milestones<br>• Range of T cell activation for<br>diverse tumor antigens<br>• Cyno-tox study compatibility<br>• StableHu optimized<br>sequence reduces<br>downstream risks<br>*<br>Eli Lilly / Merus (July 2021):<br>$40M upfront, $20M<br>investment, $540M milestones,<br>royalties<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>***Amgen / Teneobio<br>(July 2021):<br>$900M upfront, $1.6B<br>downstream<br>+Gilead / MacroGenics<br>(Oct 2022):<br>$60M upfront, $1.7B<br>milestones, royalties<br>**GSK / WuXi<br>(Jan 2023):<br>$40M upfront, $1.46B<br>milestones, royalties |
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| Data on file 52<br>Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies<br>Hu/Cyno CD3 & T Cell<br>TCR<br>CD3<br>Engineered<br>Epitopes<br>T Cell<br>Template 1 Template 2<br>Structural-Epitope Immunization & Screening<br>StableHu Optimizer<br>AI Discovery<br>Engine<br>AI-Engineered<br>Immunogens<br>Epitope & T Cell<br>Immunization<br>Epitope &<br>CD3 Screen<br>2 Template<br>Antibodies<br>Optimized<br>Antibodies<br>SCREEN<br>Activation<br>Binding<br>1<br>2<br>3<br>4<br>5<br>6<br>(-) Ctl<br>ID |
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| Data on file 53<br>Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies<br>Epitope-Steered<br>Immunization<br>Human T Cell<br>Binding<br>Selected Hit<br>Low<br>Medium<br>High<br>StableHu<br>Mammalian-Display<br>Not Selected<br>Library<br>Screen: |
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| Data on file 54<br>EngageTx is Selected for a Diversity of T Cell Binding and Activation<br>EC50: 3 – 570 nM EC50: 2.5 – 70 nM<br>Human T Cell Binding EC50 (nM)<br>CD69 T Cell Activation EC50 (nM)<br>Hit Clones Hit Clones<br>T Cell Assay:<br>Ab Concentration (nM)<br>IFN-γ (pg/mL) TNF-⍺ (pg/mL) IL-2 (pg/mL)<br>ID<br>1<br>2<br>3<br>5<br>(-) Ctl<br>4<br>SP34<br>Gen1 benchmark SP34 Gen 1 benchmark<br>Binding Activation Cytokines |
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| 55<br>ShieldTx<br>Antibody masking technology for<br>delivering on-epitope, on-tissue clinical<br>candidates with enhanced safety and<br>developability |
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| Diseased Tissue Healthy Tissue<br>56<br>On-Target-Off-Tissue Side Effects Severely Limit The Potential of Existing And<br>Future Antibodies<br>Even exquisitely specific antibodies fail<br>in clinical trials by doing exactly what they<br>are asked to do – hit the target. The problem<br>often lies in the target being also expressed<br>on healthy tissue.<br>Many potential targets remain unexplored<br>as a drug target for fear of on-epitope off-tissue side effects.<br>The challenge: how do we achieve disease<br>tissue specificity while avoiding healthy tissue<br>expressing the same epitope?<br>“On epitope,<br>on tissue”<br>therapy<br>“On epitope,<br>off tissue”<br>therapy<br>”(…) targeting antibody delivery to selected organs and tissues (…) represents a major unmet challenge that if ultimately solved may rewrite<br>medical textbooks" - Paul J. Carter and Arvind Rajpal, Cell, 2022. |
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| 57<br>Our Engineered Epitopes Provide an Integrated Solution for Identifying And<br>Subsequently Masking Antibodies<br>Diseased Tissue<br>“On-epitope,<br>off-tissue”<br>therapy<br>Healthy Tissue<br>DME<br>activation<br>“On-epitope,<br>on-tissue”<br>therapy<br>H+<br>DME: Disease Micro Environment<br>Antibodies are activated by<br>the removal of the mask in<br>the diseased tissue.<br>Masks can be removed by<br>tumor-specific enzymes,<br>pH, redox state, and<br>disease-specific<br>metabolites.<br>The technology can<br>be employed for<br>other indications i.e.<br>inflammatory and<br>auto-immune<br>diseases.<br>Antibodies remain<br>inactive in healthy<br>tissue |
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| 58<br>Masked Antibodies are a Proven Concept and iBio’s Platform has the Potential<br>to Solve Key Remaining Challenges<br>THE PROBLEM OUR SOLUTION<br>1 Separate antibody and mask<br>discovery process is inefficient<br>Co-discovery of epitope-steered antibody<br>and mask is more efficient<br>Discovery<br>process<br>2<br>Separate discovery processes does<br>not co-evolve an optimal antibody,<br>mask, linker combination<br>Co-evolution of libraries of antibody, mask<br>and linker for maximized effectiveness of<br>masking and unmasking<br>Masking<br>performance<br>3<br>Antibody + mask + linker<br>combinations not screened for high<br>developability in production cell<br>lines<br>Mammalian-display libraries of antibody,<br>mask and linker combinations screened for<br>developability in production CHO cell lines<br>Developability<br>4<br>Random peptide or anti-idiotype masks<br>increase masked antibody<br>immunogenicity risk<br>Engineered epitope masks are designed<br>with intention to maximize the natural<br>sequence of the epitope and minimize<br>immunogenicity<br>Immunogenicity |
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| 59<br>Anti-Trop-2 x CD3<br>Bi-Specific Antibody against Tumor-Specific Trop-2 Cancer Cells |
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| Gilead acquired<br>Immunomedics<br>(Sept 2020):<br>$21Bn Payment<br>Trodelvy: Approval<br>60<br>Trop-2 x CD3 Bi-Specific Antibody Potentially for Head & Neck and Other<br>Cancer<br>Select killing cancer cells<br>that up-regulate Trop-2<br>expression while<br>improving safety margin<br>in reducing cytokine<br>release syndrome (CRS)<br>• Head & neck cancer<br>• Lung cancer<br>• Ovarian cancer<br>• Breast cancer<br>• Pancreatic cancer<br>Target Mechanism Potential Indications<br>• Novel Trop-2 epitope with extreme high<br>affinity to target<br>• Trop-2 binder with mouse/cyno/human<br>cross reactive enables early safety<br>profile optimization<br>• Optimal iBio CD3 engager with low CRS<br>and cyno/human cross reactive<br>Differentiation / Opportunity<br>Recent Trop-2 ADC Transactions & Milestones<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>AstraZeneca – Daiichi<br>Sankyo<br>(July 2020):<br>Upfront $1Bn; up to $4Bn<br>approval milestones<br>Pyramid– GeneQuantum<br>(April 2023):<br>Pre-clinical: $20M<br>upfront; $1B milestones<br>Merck-Kelun<br>(Dec 2022):<br>Pre-clinical: $47M<br>upfront; $1.36Bn<br>milestones |
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| Tumor cells show significantly<br>increased Trop-2 expression<br>Tumor cell death with<br>high Trop-2 expression<br>Trop-2 x CD3<br>binds to tumor cells<br>Trop-2 x CD3 recruits<br>T cells to kill tumor cells<br>61<br>Trop-2 x CD3 Bi-Specific Antibody Selective Target Overexpress Trop-2 Cancer<br>Cells<br>Trop-2<br>Tumor cell<br>Healthy Cell<br>Tumor cell<br>Tumor cell<br>Redirected tumor lysis<br>CD3+ T cell<br>Granzyme,<br>Perforin |
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| 62<br>iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low<br>Cytokine Release<br>62<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>20<br>40<br>60<br>80<br>100<br>Ab (nM)<br>% of Cell Killing<br>ID EC50<br>(pM)<br>Cmax<br>(% killing)<br>SD-753019 1.4 92%<br>SD-231831 7.2 92%<br>SD-753019 (Trop-2 x CD3SP34 Gen1)<br>SD-231831 (Trop-2 x CD3iBio)<br>SD-011595 (Control x CD3SP34 Gen1)<br>SD-590636 (Control x CD3iBio)<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>20000<br>40000<br>60000<br>IFNγ<br>Concentration (nM)<br>Concentration (pg/mL)<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>100<br>200<br>300<br>400<br>IL-2<br>Concentration (nM)<br>Concentration (pg/mL)<br>0.0001 0.001 0.01 0.1 1 10<br>0<br>500<br>1000<br>1500<br>TNFα<br>Concentration (nM)<br>Concentration (pg/mL)<br>Minimal Cytokine Release<br>Potent Cancer Cell Killing<br>Data on file |
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| 63<br>A Single Dose of iBio’s Bispecific Trop-2 x CD3 Antibody Induces Tumor<br>Regression in a Humanized Mouse Cancer Model<br>0 7 14<br>0<br>50<br>100<br>150<br>200<br>250<br>Days after tumor implantation<br>Tumor volume (mm<br>3<br>)<br>Vehicle<br>SD-231831 (1 mg/kg)<br>Trop-2 x CD3iBio<br>*<br>*<br>*<br>* p<0.05 vs vehicle<br>Single dose<br>SD-231831<br>36% tumor<br>regression<br>Day -14 Day 0 Day 7<br>hPBMC<br>engraftment<br>Test article<br>dosing (i.v.)<br>Tumor<br>implantation<br>Data on file |
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| 64<br>Conditionally Activated<br>Anti<br>-MUC16 x CD3<br>Bispecific Antibodies<br>Targeting the Non<br>-Shed<br>MUC16 Region<br>Leveraging iBio’s Epitope Steering,<br>ShieldTx, and EngageTx Technologies |
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| +Regeneron MUC16xCD3<br>(Sept 2022):<br>Ph. 1 31% ORR<br>Ph. 2 enrollment<br>*Regeneron, 2seventy name the target of their first solid tumor CAR-T, aim for 2023 IND<br>** Liu et al., An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer<br>***Eureka Therapeutics Announces Exclusive License Agreement between Memorial Sloan Kettering Cancer Center and Juno Therapeutics for Use of a Novel, Fully-Human MUC16 Binder in CAR T Cell Immunotherapy +Novel Regeneron Bispecific Antibodies Show Encouraging Anti-Tumor Activity in Two Advanced Solid Tumors<br>65<br>MUC16 Potentially for Ovarian and Other Cancers<br>Bind a membrane-proximal MUC16 epitope<br>Membrane-proximal<br>binding avoids epitope<br>elimination by tumors<br>Bind a non-glycosylated<br>epitope to avoid altered<br>glycosylation on tumors<br>• Ovarian<br>• Uterine<br>• Pancreatic<br>Target Mechanism Potential Indications<br>• MUC16 epitope avoids<br>primary modes of tumor<br>evasion<br>• Enabling modalities: T Cell<br>engager, ADC, CAR-T<br>Differentiation / Opportunity<br>Recent Transactions & Milestones<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>***Eureka – Juno/BMS<br>(Jan 2016):<br>CAR T Ph. 1 ongoing<br>*2seventy – Regeneron<br>(Jan 2022):<br>CAR T 2023 IND planned<br>**Genentech (Dec 2021):<br>ADC Ph. 1: Favorable<br>safety & efficacy |
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| 66<br>MUC16 Is Overexpressed and Shed by Tumor Cells<br>O-glycosylation N-glycosylation<br>MUC16<br>epitope<br>shedding<br>Shedding eliminates<br>the epitope and<br>creates an antigen sink<br>for most MUC16<br>antibodies<br>Antibodies that bind<br>the non-shed domain<br>maintain activity<br>N-terminal and<br>tandem repeat (TR)<br>domains that are shed<br>Tumor associated<br>epitope that is not shed<br>Ovarian<br>cancer cells |
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| Weeks 1–2 Weeks 3–4 Week 5<br>67<br>Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding<br>Engineered Epitope Prime + MUC16 Cell Boost AI Discovery<br>Engine<br>MUC16<br>Engineered<br>Epitope<br>Structural-epitope Immunization & Screening<br>Engineered Epitope<br>ELISA Screen<br>MUC16<br>OVCAR-3 MUC16high<br>Cell Binding Screen<br>higher cell binding<br>MEM<br>Nanoparticle<br>MUC16<br>Expressing Cells MEM + Cells<br>Hybridoma<br>Screen<br>Non-shed<br>Aglycosylated<br>Epitope |
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| 68<br>Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope<br>Closest to the Membrane<br>1D7 8G4 21G6<br>Hits do not bind shed 230-mer<br>Hits bind non-glycosylated non-shed 29-mer<br>binding<br>time<br>O-glycosylation N-glycosylation<br>N-terminal and<br>tandem repeat (TR)<br>domains that are shed<br>Epitope<br>KD = 8.0 nM KD = 5.4 nM KD = 14 nM<br>Aglycosylated<br>non-shed<br>29-mer<br>Shed<br>230-mer<br>Data on file |
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| 69<br>Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to<br>Regeneron Benchmark<br>Regeneron<br>benchmark<br>Clone ID:<br>Secondary Only<br>Unstained<br>OVCAR-3 Cells<br>8G4<br>top clone<br>higher cell binding<br>Mode Normalized<br>Data on file |
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| 70<br>8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in<br>a Fully Human Framework<br>8G4 with fully human framework<br>reduces immunogenicity risk<br>Glycosylated MUC16 membrane-proximal epitope SPR:<br>KD = 5.1 nM<br>Iso. Ctl<br>OVCAR-3 Cells<br>Epitope<br>binding<br>Cell<br>binding<br>higher cell binding<br>Data on file |
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| 71<br>Efficient Expression with 2x2 Format: Anti-CD3 x MUC16 Bispecific<br>T-Cell Engagers<br>scFv-Fc 2x2<br>Anti-MUC16<br>TAA<br>Anti-CD3<br>(EngageTx)<br>CD3<br>MUC16<br>TAA<br>T Cell Tumor<br>Cell<br>T Cell mediated killing |
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| EC50 = 14 nM EC50 = 62 nM<br>EC50 = 19 nM EC50 = 126 nM<br>Data on file 72<br>2X2 Anti-CD3 X MUC16 T Cell Engagers Stimulate T Cells in Donor PBMCs<br>EC50 >> 100 nM<br>EC50 >> 100 nM<br>MUC16 Arm 1 (-)CD3 Arm only<br>Epitope-Steered<br>Immunized Hit<br>StableHu<br>Hit<br>CD69 MFI<br>Concentration (nM)<br>MUC16 Arm 2<br>CD3 Arms<br>MUC16 Arms |
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| EC50 = 4.0 nM EC50 = 2.5 nM<br>EC50 = 5.2 nM EC50 = 5.2 nM<br>Data on file 73<br>2X2 Anti-CD3 X MUC16 T Cell Engagers Kill OVCAR-3 Ovarian Cancer Cells<br>EC50 >> 100 nM<br>EC50 >> 100 nM<br>MUC16 Arm 1 (-)CD3 Arm only<br>Epitope-Steered<br>Immunized Hit<br>StableHu<br>Hit<br>Concentration (nM)<br>MUC16 Arm 2<br>CD3 Arms<br>MUC16 Arms<br>% Specific Killing |
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| Data on file 74<br>ShieldTx Engineered Epitope Mask Conditionally Activates MUC16<br>and CD3 Hits<br>Mask Cleavage<br>No Mask<br>Mask (–MMP9)<br>Mask (+MMP9)<br>MMP<br>protease<br>Engineered Epitope<br>Mask Intact<br>Inactive<br>Antibody<br>Active<br>Antibody<br>Anti-MUC16 hit<br>Anti-CD3 hit<br>MUC16<br>Binding Response<br>CD3<br>Binding Response<br>time (s) |
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| 75<br>Anti-EGFRvIII<br>High ADCC mAb Against<br>Tumor-Specific EGFRvIII Cells |
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| **Seagen / LAVA Therapeutics<br>(Sep 2022):<br>$50M upfront,<br>$650M milestones<br>***Taiho / Cullinan Oncology<br>(May 2022):<br>$275M upfront,<br>$130M milestones<br>* Pierre Fabre / Scorpion: Scorpion licensed two preclinical-stage programs to Pierre Fabre which are targeted to specific EGFR mutations in lung cancer.<br>**Seagen transaction with LAVA Therapeutics was an exclusive license to LAVA-1223 (EGFR program), plus additional projects using Lava’s platform.<br>***Taiho transaction to acquire Cullinan Oncology’s subsidiary, Cullinan Pearl, which has worldwide rights outside of Japan to CLN-081/TAS6417 (EGFR mutant mAb).<br>76<br>EGFRvIII Potentially for Glioblastoma and Other Cancers<br>Binding a tumor-specific mutation of<br>EGFR variant III with an<br>afucosylated<br>antibody for high<br>ADCC.<br>EGFRvIII is constantly<br>“switched on” which<br>can lead to the<br>development of a<br>range of different<br>cancers.<br>• Glioblastoma<br>• Head & neck cancer<br>• Non-small cell lung cancer<br>Target Mechanism Potential Indications<br>• Novel EGFRvIII high ADCC<br>mechanism, potentially further<br>reducing toxicity & expanding<br>therapeutic window<br>• Other enabling modalities: T Cell<br>engager, ADC, CAR-T<br>Differentiation / Opportunity<br>Recent Transactions & Milestones<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>*<br>Pierre Fabre / Scorpion<br>(Apr 2023):<br>$65M upfront,<br>$553M milestones |
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| Skin toxicity<br>No skin damage<br>Data on file 77<br>iBio’s Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells and Not<br>EGFR1-Expressing Cells in Healthy Tissues<br>iBio mAb binding<br>specifically to EGFRvIII<br>Tumor Size<br>Reduction<br>iBio mAb<br>doesn’t bind to<br>EGFR1 in skin<br>Non-EGFRvIII<br>specific mAb<br>binds to EGFR1<br>in skin<br>iBio mAb binding<br>specifically to EGFRvIII<br>Tumor Size<br>Reduction<br>Non EGFRvIII specific mAbs kill cancer cells but can cause toxicity by binding to EGFR1 in skin cells<br>iBio’s EGFRvIII-specific mAb exclusively kills cancer cells |
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| Data on file 78<br>iBio’s EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells<br>iBio EGFRvIII mAbs bind<br>recombinant EGFRvIII<br>which leads to<br>tumor cell killing<br>but not binding wild-type<br>EGFR1<br>and thus not affecting<br>healthy cells |
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| 79<br>iBio’s EGFRvIII-Specific High-ADCC Antibody Inhibits Tumor Growth in an<br>EGFRvIII Tumor Xenograft Mouse Model<br>Day -7 Day 0 Day 0, 3, 8,<br>11, 14, 17<br>Tumor<br>implantation<br>Subsequent<br>dosing<br>Test article<br>dosing (i.v.)<br>0 5 10 15 20 25<br>0<br>200<br>400<br>600<br>800<br>1000<br>1200<br>1400<br>1600<br>1800<br>Days after treatment<br>Tumor Volume (mm<br>3<br>)<br><br><br><br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>*<br>* p<0.05 vs negative control<br>36% tumor<br>Inhibition<br>43% tumor<br>Inhibition<br><br>hIgG1 negative control (30 mg/kg)<br>Cetuximab (30 mg/kg)<br>SD-233883-afuc (30 mg/kg) |
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| 80<br>Market-Tested<br>Potential in Immuno-Oncology<br>Competitor Early-Stage Deals<br>Signal Promising Opportunities |
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| * Acquisition / Merger + License or collaboration 81<br>Market-Tested Potential: Immuno-Oncology Early-Stage Deals<br>CCR8<br>Coherus / Surface Oncology*:<br>acquired for $65M<br>JUN 2023<br>Pre-2020 2021 2022 2023<br>CCR8<br>Gilead / Jounce+:<br>$85M upfront,<br>$35M equity investment,<br>$685M milestones<br>SEP 2020<br>FEB 2021<br>PD-1 agonist<br>Merck / Pandion*:<br>acquired for $1.85B<br>SEP 2018<br>Roche / Tusk Therapeutics*:<br>$81M upfront,<br>$677M milestones<br>CD25<br>JUN & DEC 2021<br>CCR8<br>Fibrogen / HiFiBio+:<br>$25M option fee,<br>$35M option exercise,<br>$1.1B milestones SEP 2022<br>EGFRvIII<br>Seagen / LAVA Therapeutics+:<br>$50M upfront, $650M milestones<br>AUG 2022<br>PD-1 agonist<br>Gilead / Mirobio*:<br>acquired for $405M<br>MAY 2022<br>EGFRvIII<br>Taiho / Cullinan Oncology+:<br>$275M upfront, $130M milestones<br>OCT 2022<br>CD3<br>Gilead / MacroGenics+:<br>$60M upfront, $1.7B milestones<br>JUL 2021<br>CD3<br>Eli Lilly / Merus+:<br>$40M upfront, $20M investment<br>$540M milestones<br>JUL 2021<br>CD3<br>Amgen / Teneobio*:<br>$900M upfront,<br>$1.6B milestones<br>2024<br>JAN 2023<br>CD3<br>GSK / WuXi Biologics+:<br>$40M upfront,<br>$1.46B milestones<br>CCR8<br>Gilead / Jounce+:<br>$67M for remaining stake in<br>CCR8 program<br>JAN 2023<br>TROP-2<br>Gilead / Immunomedics*:<br>acquired for $21B<br>SEP 2020<br>TROP-2<br>AstraZeneca / Daiichi+:<br>$1B upfront (some deferred),<br>$5B milestones<br>JUL 2020<br>APR 2023<br>EGFRvIII<br>Pierre Fabre / Scorpion+:<br>$65M upfront,<br>$553M milestones<br>ShieldTx<br>Sanofi / Amunix*<br>acquired for $1B, $225M milestones<br>DEC 2021 ShieldTx<br>Regeneron / Cytomx+<br>$30M upfront, $2B milestones<br>NOV 2022<br>APR 2024<br>Regeneron / 2Seventy Bio:<br>multi-asset purchase for<br>$5M upfront w/milestone<br>MUC16<br>TROP-2<br>BioNTech / Duality Biologics+:<br>$170M upfront, $1.5B milestones<br>APR 2023<br>TROP-2<br>Merck / Harpoon*:<br>acquired for $680M<br>MAR 2024<br>TROP-2<br>Biohaven / Pyramid*:<br>acquired for $55M<br>JAN 2024<br>DEC 2023<br>Neoleukin / Neurogene*:<br>all-stock transaction<br>CD25 |
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