8-K

iBio, Inc. (IBIO)

8-K 2024-10-23 For: 2024-10-23
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Added on 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): October 23, 2024

iBio, Inc.

(Exact name of registrant as specified in charter)

Delaware

(State or other jurisdiction of incorporation)

001-35023 26-2797813
(Commission File Number) (IRS Employer Identification No.)

11750 Sorrento Valley Road , Suite 200

San Diego , California 92121

(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:

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 9.01. **** Financial Statements and Exhibits.

(d)    Exhibits.

The following exhibits are furnished with this Current Report on Form 8-K:

Exhibit No. Description
99.1 Corporate Presentation of iBio, Inc., dated October 2024
104 Cover Page Interactive Data File (the cover page XBRL tags are embedded within the inline XBRL document)

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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.

Date: October 23, 2024 IBIO, INC.
By: /s/ Marc A. Banjak
Name: Marc A. Banjak
Title: Chief Legal Officer

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Exhibit 99.1

October 2024<br>Tomorrow’s Precision<br>Antibody Therapeutics<br>Powered by Machine<br>Learning
2<br>Forward-looking Statements<br>Certain statements in this presentation constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as<br>amended. Words such as "may," "might," "will," "should," "believe," "expect," "anticipate," "estimate," "continue," "predict," "forecast," "project," "plan," "intend"<br>or similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. These forward-looking statements are<br>based upon current estimates. While iBio, Inc., a Delaware corporation (including its consolidated subsidiaries, “iBio,” the “Company,” “we,” “us” or “our”)<br>believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based<br>on information available to us on the date of this presentation. These forward-looking statements are subject to various risks and uncertainties, many of<br>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<br>any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the<br>Company’s ability to obtain regulatory approvals for commercialization of its product candidates, or to comply with ongoing regulatory requirements,<br>regulatory limitations relating to its ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates<br>in the marketplace and the successful development, marketing or sale of products, its ability to attain license agreements, the continued maintenance and<br>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<br>research and development activities, competition, its ability to retain its key employees or maintain its NYSE American listing, and the other factors discussed<br>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<br>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<br>statements contained in this presentation on account of new information, future events, or otherwise, except as required by law.
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*U.S. Patent No. 11,545,238 (issued January 3, 2023)<br>https://www.globenewswire.com/news-release/2023/09/06/2738625/0/en/Monoclonal-Antibodies-Market-is-expected-to-reach-USD-612-2-Billion-by-2032-growing-at-a-CAGR-of-12-3-from-2022-to-2032.html 3<br>Next Generation Antibody<br>company utilizing our<br>proprietary Machine<br>Learning Antibody Engine<br>to create first-in-class and<br>best-in-class drugs for<br>hard-to-drug molecules<br>iBio Machine Learning Engine<br>Antibody Market Potential<br>2032<br>$612bn<br>2022<br>$196bn<br>Epitope<br>Steering*<br>ShieldTxTM<br>StableHuTM +<br>Mammalian<br>Display<br>EngageTxTM
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4<br>2008-2020 Post Sept 2022 2023<br>Plant-Based CDMO &<br>COVID Vaccine Focus<br>Machine Learning<br>Biotech Transformation<br>Biotech Strategy<br>Execution<br>Entering Metabolic<br>Disease Space<br>Building a Leading<br>Biologics Company<br>• New Exec. Team<br>• Raised $15.1M<br>• Eli Lilly Partnership<br>• NIH Collaboration<br>• 3 Undisclosed Industry<br>Partnerships<br>• AstralBio<br>Collaboration<br>• Raised $15M PIPE<br>• PD-1 asset sale to<br>Otsuka<br>• Sold GMP Facility<br>• Raised ~$109M+ • Initiated Facility Sale<br>• Raised $5.2M<br>• Asset Acquisition of<br>• Advance multiple<br>programs into clin dev<br>• Expand indications<br>through partnerships<br>• Continue to develop<br>generative AI platform<br>2024 Future<br>Evolution of iBio: From CDMO to Machine-Learning (ML) Enabled<br>Antibody Discovery
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5<br>• Patented epitope-engineering<br>technology<br>• StableHu antibody optimizer<br>coupled with mammalian display<br>• EngageTx next generation bi-specific antibody platform<br>• ShieldTx antibody masking fully<br>integrated in technology stack<br>Technology Stack<br>Spurs Rapid<br>Preclinical Pipeline<br>• Pipeline of 6 preclinical programs of<br>hard to drug targets<br>• Targets in focus of major immuno-oncology (I/O) companies with<br>significant deal flow<br>• Promising early CMC development<br>data for lead asset IBIO-101<br>• Expansion into cardiometabolics<br>through AstralBio partnership<br>Patented AI-driven<br>discovery tech stack<br>• Strategic partnerships<br>• Proprietary preclinical pipeline ready for licensing<br>• Exclusive platform licensing for specific disease areas<br>Versatile<br>Business Model<br>Innovating with Intelligence: Unleashing Our AI-Driven Antibody Discovery
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Increase Low<br>Overall Success Rate<br>Compress Time<br>From Discovery to IND<br>Design mAbs with<br>Complex MoA<br>Pursuit of Novel<br>Biology & Targets<br>6<br>Challenges of Antibody Discovery and Development Requires Integration<br>of Individual Point Solutions<br>1. Ingelheim, B. Drug Discovery at Boehringer Ingelheim. Boehringer Ingelheim (2019).<br>2. Lyu et al., Antibody Therapeutics, September 2022<br>• Vast majority of approved<br>mAbs simply block protein<br>interaction<br>• mAbs with complex<br>Mechanisms of Action (MoAs)<br>are rare (agonistic, cell-activating, …)<br>• Typical times from Discovery<br>to IND 5-6 years1<br>• Lengthy trial and error process<br>adds significant time to Hit ID<br>• Iterative, single dimension<br>Lead Optimization (LO) is time<br>consuming<br>• Low success rate overall<br>• Poor developability of<br>development candidates (DC)<br>significantly contributes to<br>failure rate<br>Hit ID LO IND<br>Hit ID LO IND<br>• Approved mAbs only target<br>small cluster of all potential<br>drug targets<br>• 40% of all approved mAbs bind<br>to only 10 targets2
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*U.S. Patent No. 11,545,238 (issued January 3, 2023) 7<br>iBio’s Generative AI-Driven Tech Stack - Integrated Solution for Antibody<br>Discovery & Development<br>Improved<br>Developability<br>Accelerated<br>Discovery Time<br>mAbs with Complex<br>MoA<br>Epitope Engineering<br>AI Engine*<br>Engineered<br>Epitope<br>AI-Guided<br>Precision Hit<br>Proprietary<br>Human Library<br>Epitopes with<br>Desired Function<br>Epitope AI<br>Engine<br>Mechanism of<br>mAb Action<br>Target<br>Agonism<br>Protein<br>Complex<br>Stabilization<br>Conditional<br>Activation<br>Tissue<br>Specificity<br>Input<br>Sequence<br>Multi-Dimensional<br>Optimization<br>Generative<br>AI engine<br>Single-Step<br>Optimized<br>Candidates<br>Generative AI Engine<br> Creates Library Diversity<br> Translates any Input Into<br> Human Sequences<br>Mammalian Display<br> Correct mAb Assembly<br> Ensures Expression in<br> Manufacturing Cell Line<br>mAb<br>Hit<br>>><br>>><br>>><br>>><br>Highly Developable<br>Optimized Leads<br>Pursuit of Novel<br>Biology & Targets
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8<br>ML Technology Accelerates Preclinical Pipeline<br>† Patent Pending<br>*Developed with Engage Tx bispecific platform<br>PROGRAMS EARLY<br>DISCOVERY<br>LATE<br>DISCOVERY<br>LEAD<br>OPTIMIZATION<br>IND-ENABLING MODE OF ACTION - TARGET<br>CARDIO-METABOLIC<br>Collaboration<br>with AstralBio<br>Established<br>March 2024<br>Myostatin Soluble factor inhibition<br>Target 2 TBA<br>Target 3 TBA<br>Target 4 TBA<br>ONCOLOGY<br>(Solid Tumors)<br>IBIO-101† (CD25) IL-2 Sparing Mode of Action; Potential Best-in-Class<br>CCR8† Antagonism<br>Trop-2 x CD3*† Bispecific Format; Conditional Activation;<br>Potential Best-in-Class<br>EGFRvIII† Targeting Tumor Specific Epitope<br>MUC16 x CD3*† Bispecific Format; Conditional<br>Activation; Potential Best-in-Class<br>Target 5 Protein Complex Stabilization
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9<br>Our Generative AI Platform: Endorsed by Leading Partners<br>PD-1 Agonist Asset Acquired by Otsuka;<br>$52.5M Potential Milestone Payments<br>Completed R&D Collaboration to<br>Develop Lassa Fever Vaccine<br>Undisclosed<br>>$1Bn Market Cap mAb Company<br>Eli Lilly<br>R&D Agreement, Option to License Antibodies<br>Against Two Hard-to-Drug Targets<br>Otsuka<br>AstralBio<br>Undisclosed<br>>$500M Market Cap mAb Company<br>Undisclosed<br>Privately Held mAb Company<br>R&D Agreement<br>MTA*; POC Established; Engaged in Talks for<br>Follow-On Agreement<br>MTA* to Establish POC<br>NIH<br>(NIAID)<br>Exclusive License and Collaboration to Develop<br>4 targets in Obesity and Cardiometabolic<br>Disease with Option to License 3 Targets.<br>*Material Transfer Agreement<br>AI Discovery<br>Platform<br>R&D<br>Partnerships<br>Pipeline Asset<br>Sales<br>Strategic<br>Collaborations
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iBio<br>Internal Pipeline Partnership<br>Data<br>Programs Data<br>Programs<br>10<br>Seizing Future Opportunities: A Growing Pipeline and Strategic<br>Collaborations Driving Platform Development<br>Rapidly Evolving Obesity/Cardiometabolic<br>Pipeline<br>• Strong Focus on Validated<br>Biology<br>• Generative AI Platform to<br>Engineer Best-In-Class<br>Molecules<br>Monetizing Existing<br>Immuno-Oncology Pipeline<br>• Created and optimized with our generative AI platform<br>• Focus on out-licensing of preclinical pipeline assets<br>• Opportunistic advancement of candidates into clinical development<br>Through Partnerships Unlocking Hard-to-Drug Targets in Other Disease Areas<br>• Inflammation and Immunology<br>(i.e. Agonistic mAbs)<br>• Neurology (i.e. Ion Channels)<br>Utilizing the Platform for<br>Other Modalities<br>• AI Engineered Epitopes as mRNA<br>or Peptide Vaccines<br>• Hard-to-Drug Targets for ADC and<br>Cell Therapy<br>Generative<br>AI Platform
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11<br>Anticipated Collaboration Catalysts<br>2024 2025 2026 2027<br>JAN JUN DEC JAN JUN DEC JAN JUN DEC JAN<br>Cardio-metabolic<br>Pipeline<br>Collaboration<br>with AstralBio<br>Established<br>March 2024<br>Myostatin<br>(Obesity)<br>Target 2<br>(Obesity)<br>Target 3<br>(Obesity)<br>Partnerships Eli Lilly<br>Lead Selection<br>Development Candidate<br>IND-Enabling<br>Finish PC/animal<br>studies<br>Complete Non-Human Primate Data<br>Lead Development Candidate IND Filing<br>First-in-class In Vitro Data<br>IND-Enabling<br>Lead Development Candidate<br>First-in-class In Vitro Data<br>IND Filing<br>IND-Enabling<br>IND Filing<br>Research agreement work completed
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12<br>Led by Industry Veterans, Powered by Next-Gen Scientists<br>Leadership Team<br>Martin Brenner, DVM, Ph.D.<br>CEO & CSO<br>Marc Banjak<br>CLO<br>Leadership team with decades of<br>experience in pharma / biotech<br>industry and extensive deal and fund-raising expertise<br>Scientific team of new generation<br>“bi-lingual” scientists, proficient in<br>machine learning/platform<br>development, and biology<br>Deep expertise in cardiometabolic<br>disorders<br>Kristi Sarno<br>Senior VP BD<br>Felipe Duran<br>CFO
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13<br>Company Highlights Financial Highlights iBio<br>Summary • Patented machine learning<br>technology solving hard to<br>drug molecule challenges<br>• Numerous validating<br>partnerships showing proof of<br>concept<br>• Developing novel targets in<br>the Obesity/Cardiometabolic<br>space<br>• Best in class fast follower I/O<br>pipeline ready for partnering<br>• Publicly traded (NYSEA: IBIO)<br>• Approximately $14.4M in cash,<br>cash equivalents and restricted<br>cash (30 June 2024)<br>• 9,137,895 shares of common<br>stock outstanding (9 Oct 2024)<br>• Texas Manufacturing Facility sale<br>completed eliminating<br>substantial secured debt<br>• Current cash provides runway<br>through June 2025
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Appendix<br>14
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Technology Platform & Preclinical Pipeline<br>15
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16<br>Technology Stack
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17<br>iBio’s Tech Stack Aims to Solve Major Challenges in Antibody<br>Discovery & Development<br>Epitope<br>Steering<br>StableHu &<br>Mammalian Display<br>Unlocking Novel<br>Biology 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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18<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>Unlocking High-Value Drug Targets: AI-Engineered Epitopes are<br>Generalizable 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<br>19
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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>Accelerate Success: StableHu Antibody Optimization & Mammalian Display<br>Screening Propel Faster, Cost-Effective Antibody Development<br>20
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21<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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22<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)<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<br>23
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24<br>Long-Acting Anti-Myostatin
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1. Gross, K. and Brinkmann, C. (2024) Why you should not skip tailored exercise interventions when using incretin mimetics for weight loss. Frontiers in Endocrinology, (15) 2. Schuelke, M., et al (2004). Myostatin<br>Mutation Associated with Gross Muscle Hypertrophy in a Child. New England Journal of Medicine, 350(26); 3. Deng, B. (2017) The function of myostatin in the regulation of fat mass in mammals. Nutrition and<br>Metabolism, 14(29) 4. Smith, R., and Lin, B. (2013) Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders. Curr Opin Support Palliat Care. 7(4)<br>25<br>Myostatin Antagonism<br>Incretin-based therapies are becoming standard treatments for weight loss. However, up to 40% of<br>the weight lost through these medications is attributed to reductions in lean muscle mass1<br>Myostatin Profile<br>Enhancing the quality of weight loss by maintaining lean muscle mass during weight loss<br>Smad2/3<br>Smad4<br>Effects on gene transcription/protein synthesis<br>Muscle Atrophy<br>FoxO<br>• Myostatin is produced by and acts on muscle cells to<br>trigger muscle wasting<br>• Homozygous loss of function mutations lead to<br>significant muscle hypertrophy without obvious<br>deleterious health effects2<br>• Expressed as homodimer and signals through activin<br>receptors and Smad2/3 pathway<br>• Beyond muscle, myostatin plays a role in the<br>regulation of adipogenesis & leads to reduction in<br>total body fat mass, visceral & intramuscular fat3<br>4
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26<br>iBio Anti-Myostatin Antibody Promotes Muscle Fiber Formation in Human<br>Muscle Progenitor Cells<br>Red indicates marker for muscle cell growth and development (as measured by myoblast differentiation)<br>Control + Myostatin + Myostatin<br>+ iBio Anti-Myostatin mAb
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27<br>Half-life Extended Myostatin Antagonist Monoclonal Antibody<br>Key Insights Fundamental Concepts Application<br>Myostatin Inhibition<br>Established as an Effective<br>Mechanism to Increase &<br>Preserve Muscle Mass<br>First-generation Myostatin<br>Binders Lacked Specificity<br>Agents were Developed for<br>Severe Conditions like Spinal<br>Muscular Atrophy (SMA)<br>and Cancer Cachexia<br>Positioning in Obesity, a<br>More Prevalent Disease<br>Other Approaches May<br>Cause Adverse Effects &<br>Reproductive Toxicity<br>Potential Best-in-class<br>Highly Potent Binders with<br>Optimized Target Product<br>Profile for Obesity<br>• Subcutaneous Administration<br>Engineering Extended Half- • Extended Half-life<br>life to Reduce Dosing<br>Frequency
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Half-life Extended Myostatin Antagonist Monoclonal Antibody<br>28<br>Best-In-Class Profile<br>• Leverages Fc engineering with potentially<br>class-leading properties<br>• Sequence leverages iBio’s Tech Stack with<br>a known antibody that has been in ~500<br>patients<br>• Demonstrated activity, safety and low-volume subcutaneous feasible<br>• Half-life in non-human primate studies<br>predicted ~22 days supports every 2<br>months to every 3 months dosing in humans<br>Attributes<br>Myostatin<br>Development<br>Program with<br>AstralBio<br>Other Muscle<br>Sparing<br>Programs<br>Low Volume<br>Subcutaneous<br>Administration<br>X<br>Low frequency<br>dosing (once per<br>2 or 3 months)<br>X<br>Avoids<br>Reproductive Tox X<br>High potency
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29<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 releases<br>**Data presented by Roche at AACR 2023 30<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 31<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>32<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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33<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>1hCD25 animal model - Data on file.<br>* Significant vs * Significant vs Negative Control<br>hIgG1 Isotype
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34<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>*hCD25 animal model - Data on file.<br>* Significant vs Negative Control<br># Significant vs Anti-PD-1
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35<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<br>trials<br>• Discovered suitable cell lines for manufacturing MCB<br>• Established IBIO-101 CMC methodology for producing high yield, high purity,<br>stable product under cGMP conditions<br>Potential for Master Cell Bank (MCB)<br>Development From 8 Promising Cell Lines<br>Unoptimized Cell Lines Already Show<br>Promising IBIO-101 Yields
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36<br>Anti-CCR8<br>High ADCC Anti-CCR8 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>37<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 38<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 39<br>Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1<br>Antagonism 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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40<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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41<br>Unlocking the Power of Bi-Specific Antibodies<br>with EngageTx, Our Versatile CD3 mAb Panel<br>Wide Range of Affinities, NHP Cross Reactivity,<br>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>42<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 43<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 44<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 45<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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46<br>ShieldTx<br>Antibody masking technology for delivering on-epitope, on-tissue clinical candidates with enhanced<br>safety and developability
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Diseased Tissue Healthy Tissue<br>47<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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48<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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Masked Antibodies are a Proven Concept and iBio’s Platform has the Potential<br>to Solve Key Remaining Challenges<br>49<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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50<br>Conditionally Activated Anti-MUC16 x CD3 Bispecific<br>Antibodies Targeting the Non-Shed MUC16 Region<br>Leveraging iBio’s Epitope Steering, ShieldTx, and<br>EngageTx Technologies
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+Regeneron MUC16xCD3<br>(Sept 2022):<br>Ph. 1 31% ORR<br>Ph. 2 enrollment<br>51<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<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
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52<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>53<br>Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding<br>Engineered Epitope Prime + MUC16 Cell Boost<br>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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54<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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55<br>Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron<br>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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56<br>8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in a Fully<br>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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57<br>Efficient Expression with 2x2 Format: Anti-CD3 x MUC16 Bispecific T-Cell<br>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 58<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 59<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 60<br>ShieldTx Engineered Epitope Mask Conditionally Activates MUC16 and CD3<br>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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61<br>Anti-Trop-2 x CD3<br>Bi-Specific Antibody against Tumor-Specific<br>Trop-2 Cancer Cells
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Recent transactions<br>Target mechanism Potential indications Differentiation / opportunity<br>Gilead acquired<br>Immunomedics<br>(Sept 2020):<br>$21Bn Payment<br>Trodelvy: Approval<br>62<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>63<br>Trop-2 x CD3 Bi-Specific Antibody Selective Target Overexpress Trop-2<br>Cancer 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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64<br>iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low<br>Cytokine Release<br>64<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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65<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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66<br>Anti-EGFRvIII<br>High ADCC mAb Against 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>67<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>68<br>iBio’s Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells and<br>Not 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<br>Data on file
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69<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<br>Data on file
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70<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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71<br>Market-Tested Potential<br>Competitor Early-Stage Deals Signal Promising<br>Opportunities
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* Acquisition / Merger + License or collaboration 72<br>Market-Tested Potential: Immuno-Oncology Early-Stage Deals<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>CCR8<br>Coherus / Surface Oncology*:<br>acquired for $65M<br>JUN 2023<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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