0001420720false00014207202023-10-022023-10-02

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 2, 2023

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.)

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:

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

Number

 

Exhibit Description

99.1

 

iBio, Inc. Investor Presentation, dated October 2023

104

 

Cover Page Interactive Data File (the cover page XBRL tags are embedded within in 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.

Date: October 2, 2023

IBIO, INC.

 

 

 

By: 

/s/ Marc A. Banjak

 

 

Name: Marc A. Banjak

 

 

Title: General Counsel and Corporate Secretary

Exhibit 99.1

GRAPHIC

October 2023 AI-Powered Precision Antibody Therapeutics

GRAPHIC

2 Forward-looking Statements Certain statements in this presentation constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "may," "might," "will," "should," "believe," "expect," "anticipate," "estimate," "continue," "predict," "forecast," "project," "plan," "intend" or similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. These forward-looking statements are based upon current estimates. While iBio, Inc., a Delaware corporation (including its consolidated subsidiaries, “iBio,” the “Company,” “we,” “us” or “our”) believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this presentation. These forward-looking statements are subject to various risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the Company’s ability to obtain regulatory approvals for commercialization of its product candidates, or to comply with ongoing regulatory requirements, regulatory limitations relating to its ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates in the marketplace and the successful development, marketing or sale of products, its ability to attain license agreements, the continued maintenance and growth of its patent estate, its ability to establish and maintain collaborations, its ability to obtain or maintain the capital or grants necessary to fund its research and development activities, competition, its ability to retain its key employees or maintain its NYSE American listing, and the other factors discussed in the Company’s most recent Annual Report on Form 10-K and the Company’s subsequent filings with the SEC, including subsequent periodic reports on Forms 10-Q and 8-K. The information in this presentation is provided only as of today, and we undertake no obligation to update any forward-looking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law. This presentation, and any oral statements made in connection with this presentation, shall not constitute an offer to sell, or the solicitation of an offer to buy, or a recommendation to purchase any equity, debt or other securities of the Company, nor, in connection with any securities offering by the Company, will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state or jurisdiction.

GRAPHIC

* U.S. Patent No. 11,545,238 iBio’s technology stack delivers precision antibodies designed to minimize downstream development risk through AI-guided epitope-steering and mAb optimization 3 Patented* epitope-steering AI-engine allows us to target specific regions of proteins Ab-optimizing StableHu™ technology coupled with mammalian display technology speeds up Lead Optimization; potentially minimizes downstream risks EXECUTIVE SUMMARY Team of experienced AI/ML scientists and drug hunters have the skills and capabilities to quickly advance antibodies from concept to in vivo POC Lead molecules comparable to “hard-to-engineer” antibodies licensed or acquired with upfronts ranging from $35-85M and total potential values >$500M at similar stages of development EngageTx™ optimized next gen CD3 T-cell engager antibody panel with reduced cytokine release, Non-Human Primate (NHP) cross-reactivity and reduced risk for immunogenicity

GRAPHIC

• Patented* epitope engineering • AI-engineered epitope maintains target structure 1 Epitope Engineering *U.S. Patent No. 11,545,238 (issued January 3, 2023) 4 Harnessing iBio’s Tech Stack: From Precision Antibody Identification and Optimization to Tailored Bispecifics Multiple validations with difficult targets and MoAs • Mammalian-display library enriched with functional antibodies • Human sequence and optimization faster than traditional methods 3 StableHu Antibody Optimizer • Human antibody diversity • Clinically validated frameworks • Benchmarked vs. competitive libraries 2 Proprietary Antibody Library • Diminished cytokine release • NHP cross-reactivity for advanced safety assessment ahead of clinical trials • Reduced immunogenicity risk 4 EngageTx CD3 Antibody Panel

GRAPHIC

Match Engineered Structure to Target Refined for Greater Stability Optimized for Water Solubility Unlocking High-Value Drug Targets: AI-Engineered Epitopes are Generalizable to a Broad Set of Complex Structural Drug Binding Sites Junctional Epitopes Complex Secondary Structures Membrane Proteins (e.g. GPCR) Loop Display 1 2 3 AI Epitope Engine 5

GRAPHIC

Input Antibody StableHu AI-Engine Mammalian Display Output Antibody Template CDR Predict library of human CDR variants Single-cell screen mammalian display CDR library Optimized antibody with fully human CDRs Accelerate Success: StableHu Antibody Optimization & Mammalian Display Screening Propel Faster, Cost-Effective Antibody Development 6

GRAPHIC

7 EngageTx, a CD3-Based T-Cell Engager Panel, Addresses 3 Key Challenges: Cytokine Release, NHP Cross-Reactivity and Immunogenicity Risk Numerous tumor antigen arms Diverse CD3 engager arms 1 Sequence Diversity 2 Hu-Cyno Cross-Reactivity 3 Range of Cytokine Release Increased humanness and broad CD3 activity for optimized paring with tumor antigen arms Risk reduction via cyno monkey toxicity study compatibility Tailored cytokine release for expanded therapeutic window Release of cytokines TNFα, IFNγ, IL-2, (IL6) Increased cytotoxicity Reduced cytokine release Release of cytotoxic granules Granzyme, Perforin Cascade of immune activation Tumor cell death Activated T cell Tumor cell

GRAPHIC

8 From Idea To Clinical Candidate: We Believe Our Discovery Platform Improves Probability of Success, Speed, and Developability AI-powered sequence optimization to improve performance AI-powered precision targeting of conformational & sub-dominant epitopes Epitope-specific antigens built to efficiently & selectively discover antibodies AI-generated naïve antibody library, free of sequence liabilities Optimized bi-specifics leveraging broad potency range, human-monkey cross-reactivity, & sequence diversity Optimized Leads evaluated & ranked in translational disease models Epitope Engineering Proprietary Human mAb Library StableHu Antibody Optimizer EngageTx Engineered Epitope Optimized mAb Lead Pool Getting it right from the outset Precision antibody targeting takes the lengthy trial and error out of mAb discovery and improves probability of success More speed, mitigated risk Reduced number of iterative optimization steps, lower immunogenicity risk and improved developability Enhanced bispecifics control Wide potency range with reduced cytokine release and NHP cross-reactivity to strengthen preclinical safety assessment

GRAPHIC

Capitalizing on AI: We Believe Our Platform Powers a Focused, Capital Efficient Business Plan 9 AI Discovery Platform • Partner existing molecules or discovery projects against new targets • Potential for upfront, milestone payments and/or royalties Strategic Partnerships • Advancing a select few “fast followers” • Potential licensing and asset sales for other molecules Proprietary Pipeline • Exclusive licensing for non-core therapeutic areas to 3rd parties (vaccines, etc.) • Potential for upfront technology access fee and milestones plus royalties for multiple targets Third Party Collaboration

GRAPHIC

PROGRAMS EARLY DISCOVERY LATE DISCOVERY LEAD OPTIMIZATION IND-ENABLING CLINICAL Oncology IBIO-101 Trop-2 x CD3* MUC16 Target 5 EGFRvIII CCR8 Target 8 Autoimmune PD-1 10 Catalyzing Innovation: Technology Stack Spurs Rapid Pipeline Growth and Maturation in Cancer Immunotherapies Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Immuno-Oncology Autoimmune Diseases Solid Tumors *Developed with Engage Tx bispecific platform

GRAPHIC

* Acquisition / Merger + License or collaboration 11 Market-Tested Potential: Competitor Early-Stage Deals Signal Promising Opportunities for Our Pipeline FEB 2021 Pre-2019 2020 2021 2022 CCR8 Gilead / Jounce+: $85M upfront, $35M equity investment, $685M milestones SEP 2020 PD-1 agonist Merck / Pandion*: Acquired for $1.85B SEP 2018 Roche / Tusk Therapeutics*: $81M upfront, $677M milestones IBIO-101 (CD25) JUN & DEC 2021 CCR8 Fibrogen / HiFiBio+: $25M option fee, $35M option exercise, $1.1B milestones SEP 2022 EGFRvIII Seagen / LAVA Therapeutics+: $50M upfront, $650M milestones AUG 2022 PD-1 agonist Gilead / Mirobio*: Acquired for $405M MAY 2022 EGFRvIII Taiho / Cullinan Oncology+: $275M upfront, $130M milestones OCT 2022 CD3 Gilead / MacroGenics+: $60M upfront, $1.7B milestones JUL 2021 CD3 Eli Lilly / Merus+: $40M cash upfront, $20M investment, $540M milestones JUL 2021 CD3 Amgen / Teneobio*: $900M upfront, $1.6B milestones 2023 CCR8 Coherus / Surface Oncology*: Acquired for $65M JUN 2023 JAN 2023 CD3 GSK / WuXi Biologics+: $40M upfront, $1.46B milestones CCR8 Gilead / Jounce+: $67M for remaining stake in CCR8 program JAN 2023 TROP-2 Gilead / Immunomedics*: Acquired for $21B SEP 2020 TROP-2 AstraZeneca / Daiichi+: $1B upfront (some deferred), $5B milestones JUL 2020 APR 2023 EGFRvIII Pierre Fabre / Scorpion+: $65M upfront, $553M milestones

GRAPHIC

12 iBio Company Highlights • Ticker: IBIO (NYSE A); ~27.6M shares outstanding as of 6/30/23 • Reduced costs by ~67% post CDMO divestment from FY 23 Q1 to Q4 • Significantly reduced debt upon consummation of facility sale Financial AI-driven discovery tech stack • Patented epitope-engineering technology • StableHu antibody optimizer coupled with mammalian display • EngageTx next generation bi-specific antibody platform Layered Business Model • Strategic partnerships • Proprietary pipeline • Exclusive platform licensing for specific disease areas outside of I/O Pipeline of difficult to find biologics • Pipeline of 8 preclinical programs of hard to drug targets • Targets in focus of major immuno-oncology (I/O) companies with significant deal flow • Promising early CMC development data for lead asset IBIO-101

GRAPHIC

Preclinical Pipeline 13

GRAPHIC

14 IBIO-101 IL-2 Sparing Anti-CD25

GRAPHIC

Recent Transactions & Milestones *Roche acquisition of Tusk Therapeutics completed for €70M upfront, acquiring worldwide rights to anti-CD25 program. Values converted to dollars as reported in public press releases **Data presented by Roche at AACR 2023 15 IBIO-101 for Regulatory T-Cell (Treg) Depletion Depletion of immunosuppressive Tregs via antibody dependent cellular cytotoxicity (ADCC), without disrupting activation of effector T-cells (Teffs) in the tumor microenvironment • Solid tumors • Hairy cell leukemia • Relapsed mult. myeloma • Lymphoma • Head & neck cancer * Roche / Tusk Therapeutics (Sep 2018) $81M upfront, $677M milestones • IL-2 sparing anti-CD25 antibodies enables depletion of Tregs without affecting Teffs • Fast-follower to Roche’s RG6292 clinical molecule Target Mechanism Potential Indications Differentiation / Opportunity PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT **Roche RG6292 Ph1 Data (Apr 2023) Well-tolerated: manageable safety profile Confirmed MOA: Reduced intratumoral Tregs Efficacy: 29% stable disease (45% PD-L1 combo)

GRAPHIC

Data on file. Treg = Regulatory T Cells; Teff = Effector T Cells; ADCC = Antibody Dependent Cellular Cytotoxicity 16 IBIO-101 Reduces Tumor Growth in Preclinical Studies by Selectively Depleting Immunosuppressive Tregs without Affecting Cancer Killing Teffs Indiscriminate depletion of Treg + Teff TUMOR Teff 1st gen CD25 mAbs depleted immuno-suppressive Treg and immuno-stimulatory Teff Limited efficacy 2nd gen IBIO-101 selectively targets Tregs without blocking IL-2 signaling to Teffs Strong preclinical anti-tumor response IBIO Proliferation -101 Natural Killer Cell Preferential Treg depletion ADCC 1st Gen CD25 TUMOR IL-2 CD25 (IL-2Rα) JAK JAK Treg JAK JAK Teff JAK JAK Treg JAK JAK Teff IL-2 signaling Blocked IL-2 pathways IL-2

GRAPHIC

RG6292 is Roche’s monoclonal antibody that targets CD25 (IL-2Rα). IBIO-101 data on file. 17 IBIO-101 Selectively Depletes Tregs while preserving IL-2 signaling IBIO-101 potently binds recombinant CD25 which leads to Treg depletion while sparing Teffs

GRAPHIC

18 IBIO-101 Increases in Teff/Treg Ratio in Preclinical Studies Inhibiting Tumor Growth Tumor growth inhibition correlates with T-eff/T-reg ratio Potently increases T-eff/T-reg ratio1 1hCD25 animal model - Data on file. * Significant vs * Significant vs Negative Control hIgG1 Isotype

GRAPHIC

19 IBIO-101 in Combination With a Checkpoint Inhibitor Shows Greater Efficacy IBIO-101 + PD-1 Checkpoint Inhibitor In PreClinical Studies Enhances Tumor Suppression *hCD25 animal model - Data on file. * Significant vs Negative Control # Significant vs Anti-PD-1

GRAPHIC

20 IBIO-101 is an Antibody With Favorable Characteristics for CMC Development • Identified manufacturing partner to produce IBIO-101 for Phase 1&2 clinical trials • Discovered suitable cell lines for manufacturing MCB • Established IBIO-101 CMC methodology for producing high yield, high purity, stable product under cGMP conditions Potential for Master Cell Bank (MCB) Development From 8 Promising Cell Lines Unoptimized Cell Lines Already Show Promising IBIO-101 Yields

GRAPHIC

21 Anti-CCR8 High ADCC Anti-CCR8 for the Depletion of T-regulatory Cells

GRAPHIC

*Fibrogen / HiFiBio: Fibrogen purchased option to multiple programs in June 2021, then exercised the option for excl. license to CCR8 program in Dec. 2021. **Gilead / Jounce: Exclusive worldwide license to anti-CCR8 antibody. *** Coherus / Surface Oncology: acquisition, announced in June 2023, adds two clinical assets, including a phase 2 anti-IL-27 and a phase 1/2 anti-CCR8 for oncology. 22 CCR8 for Tumor-Infiltrating Treg Depletion Tumor-infiltrating Tregs highly express CCR8. iBio program targets depletion of highly immunosuppressive CCR8+ Tregs in tumor microenvironment via an ADCC mechanism. • Broadly applicable in solid tumors • Prospective combination therapy Target Mechanism Potential Indications Differentiation / Opportunity Recent Transactions & Milestones • Selective binding to CCR8 over its close homolog, CCR4 **Gilead / Jounce (Dec 2022): Original deal: $85M upfront, $35M equity investment, $685M milestones. 2023 Buyout: $67M for remaining rights. * Fibrogen / HiFiBio (Jun & Dec 2021): $25M option fee, $35M option exercise, $1.1B milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT ***Coherus / Surface (Jun 2023): Acquired for $65M

GRAPHIC

Zheng, et al. Cell 169.7 (2017): 1342-1356; Whiteside, et al. Immunology 163(4) (2021): 512-520; Kidani, et al. PNAS 119(7) (2022): e2114282119 23 CCR8+ Treg Cells Are Tumor Infiltrating and Highly Immunosuppressive Depletion of CCR8+ Treg cells has potential to evoke potent tumor immunity • Systemic inflammation • Skin toxicity • Platelet depletion/aggregation Intratumor cytotoxic T-cell activation & tumor death Adverse events iBio CCR8 specific antibody CCR8 & CCR4 nonspecific antibody CCR4+ cells killed CCR4+ cells spared

GRAPHIC

Data on file 24 Afucosylated Anti-CCR8 Antibody Exhibits High Specificity, CCL1 Antagonism and CCR8-Specific Cell Killing High Specificity CCR8 Cell Binding 0.0001 0.001 0.01 0.1 1 10 0 2 4 6 8 10 hCCR8 overexpressed cells Ab. (nM) MFI hIgG1 isotype mIgG2A isotype Anti -hCCR4 - EC50 = NA Anti-mCCR8 - EC50 = NA SD-356253 - (iBio) - EC50 = 0.78 nM SD-692676 - (GS-1811) - EC50 = 0.43 nM 0.0001 0.001 0.01 0.1 1 10 0 10 20 30 40 50 hCCR4 overexpressed cells Ab. (nM) MFI hIgG1 isotype mIgG2A isotype Anti -hCCR4 - EC50 = 42.5 nM Anti-mCCR8 - EC50 = NA SD-356253 - (iBio)- EC50 = NA SD-692676 - (GS-1811)- EC50 = NA 0.000001 0.00001 0.0001 0.001 0.01 0.1 1 10 0 10 20 30 40 CCR8 overexpressed cell Ab. (nM) % of cell killing hIgG1 hCCR4 - EC50 =NA SD-356253-(iBio) - EC50 = 0.004 nM SD-692676-(GS-1811) - EC50 = 0.002 nM PBMC-Induced CCR8 Cell Killing Potent binding to CCR8 overexpressing cells No binding to CCR4 overexpressing cells (Jounce/Gilead) (Jounce/Gilead) (Jounce/Gilead) Untreated CCL1 (7 nM) CCL1 (7 nM) + hIgG1 Iso. Ctl. Anti-hCCR8 (+)Ctl. SD-6926776-(GS-1811) Jounce/Gilead SD-356253 (iBio) CCR8-CCL1 Antagonism

GRAPHIC

25 iBio’s CCR8-Specific High ADCC Antibody Induces Tumor Regression in a Transgenic Human CCR8 Mouse Model Day -7 Day 0 Day 0, 3, 7, 10 Tumor implantation Subsequent dosing Test article dosing (i.p) 0 2 4 6 8 10 12 14 0 50 100 150 200 250 300 Days after treatment Tumor Volume (mm3 ) * * * * p<0.05 vs negative control * * +22% Tumor regression +10% Tumor regression 100 % Tumor Inhibition hIgG1 negative control (10 mg/kg) Competitor in clinic (10 mg/kg) SD-171467-afuc (10 mg/kg)

GRAPHIC

26 Unlocking the Power of Bi-Specific Antibodies with EngageTx, Our Versatile CD3 mAb Panel Wide Range of Affinities, NHP Cross Reactivity, High Developability

GRAPHIC

*Eli Lilly / Merus: Fibrogen Research collaboration using Merus’ proprietary platform to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies. ** GSK WuXi: License of WuXi’s preclininical CD3 bi-specific, plus 3 earlier stage programs ***Amgen / Teneobio: Teneobio was developing a heavy-chain only platform as well as its CD3 engager technology. TNB-585, the lead program, was in phase 1. + Gilead / MacroGenics: Gilead granted option to MGD024, a phase 1 CD3 bi-specific, plus collaboration on two additional research programs. 27 Next Generation Anti-CD3 T Cell Engagers T-cell-redirecting bispecific antibodies are a new therapeutic class that simultaneously targets CD3 on T cells and tumor antigens, inducing T cell mediated tumor cell killing • Broad solid tumor potential • Expands therapeutic options across programs Target Mechanism Potential Indications Differentiation / Opportunity Recent Transactions & Milestones • Range of T cell activation for diverse tumor antigens • Cyno-tox study compatibility • StableHu optimized sequence reduces downstream risks * Eli Lilly / Merus (July 2021): $40M upfront, $20M investment, $540M milestones, royalties PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT ***Amgen / Teneobio (July 2021): $900M upfront, $1.6B downstream +Gilead / MacroGenics (Oct 2022): $60M upfront, $1.7B milestones, royalties **GSK / WuXi (Jan 2023): $40M upfront, $1.46B milestones, royalties

GRAPHIC

Data on file 28 Dual Approaches to a Diverse Panel of Anti-CD3 Antibodies Hu/Cyno CD3 & T Cell TCR CD3 Engineered Epitopes T Cell Template 1 Template 2 Structural-Epitope Immunization & Screening StableHu Optimizer AI Discovery Engine AI-Engineered Immunogens Epitope & T Cell Immunization Epitope & CD3 Screen 2 Template Antibodies Optimized Antibodies SCREEN Activation Binding 1 2 3 4 5 6 (-) Ctl ID

GRAPHIC

Data on file 29 Libraries and Screens Discover Hu-Cyno CD3 Cross-Reactive Antibodies Epitope-Steered Immunization Human T Cell Binding Selected Hit Low Medium High StableHu Mammalian-Display Not Selected Library Screen:

GRAPHIC

Data on file 30 EngageTx is Selected for a Diversity of T Cell Binding and Activation EC50: 3 – 570 nM EC50: 2.5 – 70 nM Human T Cell Binding EC50 (nM) CD69 T Cell Activation EC50 (nM) Hit Clones Hit Clones T Cell Assay: Ab Concentration (nM) IFN-γ (pg/mL) TNF-⍺ (pg/mL) IL-2 (pg/mL) ID 1 2 3 5 (-) Ctl 4 SP34 Gen1 benchmark SP34 Gen 1 benchmark Binding Activation Cytokines

GRAPHIC

31 Anti-EGFRvIII High ADCC mAb Against Tumor-Specific EGFRvIII Cells

GRAPHIC

**Seagen / LAVA Therapeutics (Sep 2022): $50M upfront, $650M milestones ***Taiho / Cullinan Oncology (May 2022): $275M upfront, $130M milestones * Pierre Fabre / Scorpion: Scorpion licensed two preclinical-stage programs to Pierre Fabre which are targeted to specific EGFR mutations in lung cancer. **Seagen transaction with LAVA Therapeutics was an exclusive license to LAVA-1223 (EGFR program), plus additional projects using Lava’s platform. ***Taiho transaction to acquire Cullinan Oncology’s subsidiary, Cullinan Pearl, which has worldwide rights outside of Japan to CLN-081/TAS6417 (EGFR mutant mAb). 32 EGFRvIII for Glioblastoma and Other Cancers Binding a tumor-specific mutation of EGFR variant III with an afucosylated antibody for high ADCC. EGFRvIII is constantly “switched on” which can lead to the development of a range of different cancers. • Glioblastoma • Head & neck cancer • Non-small cell lung cancer Target Mechanism Potential Indications • Novel EGFRvIII high ADCC mechanism, potentially further reducing toxicity & expanding therapeutic window • Other enabling modalities: T Cell engager, ADC, CAR-T Differentiation / Opportunity Recent Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT * Pierre Fabre / Scorpion (Apr 2023): $65M upfront, $553M milestones

GRAPHIC

Skin toxicity No skin damage 33 iBio’s Anti-EGFRvIII mAbs Selectively Kill EGFRvIII-Positive Tumor Cells and Not EGFR1-Expressing Cells in Healthy Tissues iBio mAb binding specifically to EGFRvIII Tumor Size Reduction iBio mAb doesn’t bind to EGFR1 in skin Non-EGFRvIII specific mAb binds to EGFR1 in skin iBio mAb binding specifically to EGFRvIII Tumor Size Reduction Non EGFRvIII specific mAbs kill cancer cells but can cause toxicity by binding to EGFR1 in skin cells iBio’s EGFRvIII-specific mAb exclusively kills cancer cells Data on file

GRAPHIC

34 iBio’s EGFRvIII-Selective mAbs Kill Tumor Cells without Affecting Healthy Cells iBio EGFRvIII mAbs bind recombinant EGFRvIII which leads to tumor cell killing but not binding wild-type EGFR1 and thus not affecting healthy cells Data on file

GRAPHIC

35 iBio’s EGFRvIII-Specific High-ADCC Antibody Inhibits Tumor Growth in an EGFRvIII Tumor Xenograft Mouse Model Day -7 Day 0 Day 0, 3, 8, 11, 14, 17 Tumor implantation Subsequent dosing Test article dosing (i.v.) 0 5 10 15 20 25 0 200 400 600 800 1000 1200 1400 1600 1800 Days after treatment Tumor Volume (mm 3 ) * * * * * * * * * * * * * p<0.05 vs negative control 36% tumor Inhibition 43% tumor Inhibition hIgG1 negative control (30 mg/kg) Cetuximab (30 mg/kg) SD-233883-afuc (30 mg/kg)

GRAPHIC

36 Anti-MUC16 Tumor Associated Epitope Non-Shed Epitope Anti-MUC16 Antibody

GRAPHIC

+Regeneron MUC16xCD3 (Sept 2022): Ph. 1 31% ORR Ph. 2 enrollment 37 MUC16 Potential for Ovarian and Other Cancers Bind a membrane-proximal MUC16 epitope Membrane-proximal binding avoids epitope elimination by tumors Bind a non-glycosylated epitope to avoid altered glycosylation on tumors • Ovarian • Uterine • Pancreatic Target Mechanism Potential Indications • MUC16 epitope avoids primary modes of tumor evasion • Enabling modalities: T Cell engager, ADC, CAR-T Differentiation / Opportunity Recent Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT ***Eureka – Juno/BMS (Jan 2016): CAR T Ph. 1 ongoing *2seventy – Regeneron (Jan 2022): CAR T 2023 IND planned **Genentech (Dec 2021): ADC Ph. 1: Favorable safety & efficacy *Regeneron, 2seventy name the target of their first solid tumor CAR-T, aim for 2023 IND ** Liu et al., An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer ***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

GRAPHIC

38 MUC16 Is Overexpressed and Shed by Tumor Cells O-glycosylation N-glycosylation MUC16 epitope shedding Shedding eliminates the epitope and creates an antigen sink for most MUC16 antibodies Antibodies that bind the non-shed domain maintain activity N-terminal and tandem repeat (TR) domains that are shed Tumor associated epitope that is not shed Ovarian cancer cells

GRAPHIC

Weeks 1–2 Weeks 3–4 Week 5 39 Immunizations Were Steered to a MUC16 Epitope that Avoids Epitope Shedding Engineered Epitope Prime + MUC16 Cell Boost AI Discovery Engine MUC16 Engineered Epitope Structural-epitope Immunization & Screening Engineered Epitope ELISA Screen MUC16 OVCAR-3 MUC16high Cell Binding Screen higher cell binding MEM Nanoparticle MUC16 Expressing Cells MEM + Cells Hybridoma Screen Non-shed Aglycosylated Epitope

GRAPHIC

40 Top Three Hit Clones Bind the Non-Glycosylated MUC16 Epitope Closest to the Membrane 1D7 8G4 21G6 Hits do not bind shed 230-mer Hits bind non-glycosylated non-shed 29-mer binding time O-glycosylation N-glycosylation N-terminal and tandem repeat (TR) domains that are shed Epitope KD = 8.0 nM KD = 5.4 nM KD = 14 nM Aglycosylated non-shed 29-mer Shed 230-mer Data on file

GRAPHIC

41 Top MUC16 Clone 8G4 Binds OVCAR-3 Cells Comparable to Regeneron Benchmark Regeneron benchmark Clone ID: Secondary Only Unstained OVCAR-3 Cells 8G4 top clone higher cell binding Mode Normalized Data on file

GRAPHIC

42 8G4 Clone Maintains OVCAR-3 Cell and MUC16 Epitope Binding in a Fully Human Framework 8G4 with fully human framework reduces immunogenicity risk Glycosylated MUC16 membrane-proximal epitope SPR: KD = 5.1 nM Iso. Ctl OVCAR-3 Cells Epitope binding Cell binding higher cell binding Data on file

GRAPHIC

43 Anti-Trop-2 x CD3 Bi-Specific Antibody against Tumor-Specific Trop-2 Cancer Cells

GRAPHIC

Recent transactions Target mechanism Potential indications Differentiation / opportunity Gilead acquired Immunomedics (Sept 2020): $21Bn Payment Trodelvy: Approval 44 Trop-2 x CD3 Bi-Specific Antibody for Head & Neck and Others Cancer Select killing cancer cells that up-regulate Trop-2 expression while improving safety margin in reducing cytokine release syndrome (CRS) • Head & neck cancer • Lung cancer • Ovarian cancer • Breast cancer • Pancreatic cancer Target Mechanism Potential Indications • Novel Trop-2 epitope with extreme high affinity to target • Trop-2 binder with mouse/cyno/human cross reactive enables early safety profile optimization • Optimal iBio CD3 engager with low CRS and cyno/human cross reactive Differentiation / Opportunity Recent Trop-2 ADC Transactions & Milestones PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT AstraZeneca – Daiichi Sankyo (July 2020): Upfront $1Bn; up to $4Bn approval milestones Pyramid– GeneQuantum (April 2023): Pre-clinical: $20M upfront; $1B milestones Merck-Kelun (Dec 2022): Pre-clinical: $47M upfront; $1.36Bn milestones

GRAPHIC

Tumor cells show significantly increased Trop-2 expression Tumor cell death with high Trop-2 expression Trop-2 x CD3 binds to tumor cells Trop-2 x CD3 recruits T cells to kill tumor cells 45 Trop-2 x CD3 Bi-Specific Antibody Selective Target Overexpress Trop-2 Cancer Cells Trop-2 Tumor cell Healthy Cell Tumor cell Tumor cell Redirected tumor lysis CD3+ T cell Granzyme, Perforin

GRAPHIC

46 iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low Cytokine Release 46 0.0001 0.001 0.01 0.1 1 10 0 20 40 60 80 100 Ab (nM) % of Cell Killing ID EC50 (pM) Cmax (% killing) SD-753019 1.4 92% SD-231831 7.2 92% SD-753019 (Trop-2 x CD3SP34 Gen1) SD-231831 (Trop-2 x CD3iBio) SD-011595 (Control x CD3SP34 Gen1) SD-590636 (Control x CD3iBio) 0.0001 0.001 0.01 0.1 1 10 0 20000 40000 60000 IFNγ Concentration (nM) Concentration (pg/mL) 0.0001 0.001 0.01 0.1 1 10 0 100 200 300 400 IL-2 Concentration (nM) Concentration (pg/mL) 0.0001 0.001 0.01 0.1 1 10 0 500 1000 1500 TNFα Concentration (nM) Concentration (pg/mL) Minimal Cytokine Release Potent Cancer Cell Killing

GRAPHIC

47 A Single Dose of iBio’s Bispecific Trop-2 x CD3 Antibody Induces Tumor Regression in a Humanized Mouse Cancer Model 0 7 14 0 50 100 150 200 250 Days after tumor implantation Tumor volume (mm 3 ) Vehicle SD-231831 (1 mg/kg) Trop-2 x CD3iBio * * * * p<0.05 vs vehicle Single dose SD-231831 36% tumor regression Day -14 Day 0 Day 7 hPBMC engraftment Test article dosing (i.v) Tumor implantation

GRAPHIC

48 PD-1 Agonist Supports Restoration of Homeostasis for Inflammatory Diseases

GRAPHIC

49 PD-1 Agonist to Alleviate Inflammatory Disease Selectively agonize PD-1 without antagonizing the natural PD-1:PD-L1 anti-inflammatory interaction • Rheumatoid arthritis • Broad application in treating inflammatory disease Target mechanism Potential indications Differentiation / opportunity Recent Transactions & Milestones • Potent PD-1 agonism vs. benchmarks with in vitro reporter and primary cell assays **Gilead / Mirobio (Aug 2022): Acquired for $405M *Merck / Pandion (Feb 2021): Acquired for $1.85B PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT Eli Lilly (May 2023): Positive Ph 2a efficacy in RA patients • Merck / Pandion: At the time of acquisition, Pandion pipeline including an IL-2 fusion drug in phase 1a, as well as group of preclinical PD-1 agonists. ** Gilead / Mirobio: Mirobio pipeline at time of deal included a phase 1 BTLA (checkpoint) agonist as well as preclinical programs which included a PD-1 agonist.

GRAPHIC

PD-1 PD-L1 TCR MHC T-cell Antigen presenting cell 50 Antagonizing PD-1 with PD-L1 Blocking Worsens Autoimmunity and Systemic Inflammation Inflammatory Disease Tissue Healthy Tissue Increased & systemic inflammation No T-cell inhibition No T-cell inhibition Worsened Strong T-cell inhibition Weak T-cell inhibition Autoimmunity PD-1 Antagonist Antibody

GRAPHIC

51 Agonizing PD-1 Without Blocking PD-L1 Restores Activated T-Cell Suppression Diseased Tissue Reduced inflammation Healthy Tissue Low-inflammation preserved PD-1 PD-L1 Strong TCR MHC T-cell inhibition T-cell Inflammatory Disease Tissue Healthy Tissue Weak T-cell inhibition Strong T-cell inhibition Strong T-cell inhibition Improved Autoimmunity Antigen presenting cell PD-1 Agonist Antibody

GRAPHIC

Benchmark Antibodies PD-1 Agonist Antibodies 52 In vitro PD-1 Agonism Equals or Surpasses Benchmarks and PD-L1 Ab ID EC50 (nM) SD-671823 0.88 SD-300670 0.31 SD-030629 0.36 SD-136366 0.28 SD-759028 0.52 SD-313018 (bispecific) 0.30 AnaptysBio APE12095 17.4 BMS/Celgene PD1AB6 0.76 IgG1 isotype control inactive SD-671823 SD-300670 SD-030629 SD-136366 SD-759028 SD-313018 (bispecific) AnaptysBio APE12095 BMS/Celgene PD1AB6 IgG1 isotype control Tetravalent Bivalent x x Data on file

GRAPHIC

Data on file 53 Primary T-Cell Suppression Equals or Surpasses Benchmarks and PD-L1 IL-2 at 24 hrs. % IL-2 Release Mean of 6 donors 0 100 200 Anti-HEL IgG1 Isotype Control CD69 at 72 hrs. CD69 MFI Mean of 6 donors 0 100 200 300 Anti-HEL IgG1 Isotype Control iBio Molecules Benchmark Molecules Natural Agonist

v3.23.3
Document And Entity Information
Oct. 02, 2023
Cover [Abstract]  
Document Type 8-K
Written Communications false
Document Period End Date Oct. 02, 2023
Soliciting Material false
Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Entity Registrant Name iBio, Inc.
Entity Incorporation, State or Country Code DE
Securities Act File Number 001-35023
Entity Tax Identification Number 26-2797813
Entity Address, Address Line One 8800 HSC Parkway
Entity Address, City or Town Bryan
Entity Address, State or Province TX
Entity Address, Postal Zip Code 77807
City Area Code 979
Local Phone Number 446-0027
Title of 12(b) Security Common Stock
Trading Symbol IBIO
Security Exchange Name NYSEAMER
Entity Emerging Growth Company false
Entity Central Index Key 0001420720
Amendment Flag false
v3.23.3
N-2
Oct. 02, 2023
Cover [Abstract]  
Entity Central Index Key 0001420720
Amendment Flag false
Securities Act File Number 001-35023
Document Type 8-K
Entity Registrant Name iBio, Inc.
Entity Address, Address Line One 8800 HSC Parkway
Entity Address, City or Town Bryan
Entity Address, State or Province TX
Entity Address, Postal Zip Code 77807
City Area Code 979
Local Phone Number 446-0027
Entity Emerging Growth Company false

Grafico Azioni iBio (AMEX:IBIO)
Storico
Da Apr 2024 a Mag 2024 Clicca qui per i Grafici di iBio
Grafico Azioni iBio (AMEX:IBIO)
Storico
Da Mag 2023 a Mag 2024 Clicca qui per i Grafici di iBio