8-K
iBio, Inc. (IBIO)
8-K
2023-10-02
For: 2023-10-02
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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): 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:
| <br><br> | |
|---|---|
| Exhibit<br><br>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
| October 2023<br>AI-Powered<br>Precision Antibody<br>Therapeutics |
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| 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. This presentation, and any<br>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<br>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<br>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<br>securities laws of such state or jurisdiction. |
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| * U.S. Patent No. 11,545,238<br>iBio’s technology stack<br>delivers precision antibodies<br>designed to minimize<br>downstream development<br>risk through AI-guided<br>epitope-steering and mAb<br>optimization<br>3<br>Patented* epitope-steering AI-engine allows us to<br>target specific regions of proteins<br>Ab-optimizing StableHu™ technology coupled with<br>mammalian display technology speeds up Lead<br>Optimization; potentially minimizes downstream risks<br>EXECUTIVE SUMMARY<br>Team of experienced AI/ML scientists and drug<br>hunters have the skills and capabilities to quickly<br>advance antibodies from concept to in vivo POC<br>Lead molecules comparable to “hard-to-engineer”<br>antibodies licensed or acquired with upfronts ranging<br>from $35-85M and total potential values >$500M at<br>similar stages of development<br>EngageTx™ optimized next gen CD3 T-cell engager<br>antibody panel with reduced cytokine release,<br>Non-Human Primate (NHP) cross-reactivity and<br>reduced risk for immunogenicity |
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| • Patented* epitope engineering<br>• AI-engineered epitope maintains<br>target structure<br>1 Epitope Engineering<br>*U.S. Patent No. 11,545,238 (issued January 3, 2023) 4<br>Harnessing iBio’s Tech Stack: From Precision Antibody Identification and<br>Optimization to Tailored Bispecifics<br>Multiple validations<br>with difficult targets<br>and MoAs<br>• Mammalian-display library enriched<br>with functional antibodies<br>• Human sequence and optimization<br>faster than traditional methods<br>3 StableHu<br>Antibody Optimizer<br>• Human antibody diversity<br>• Clinically validated frameworks<br>• Benchmarked vs. competitive libraries<br>2 Proprietary Antibody<br>Library<br>• Diminished cytokine release<br>• NHP cross-reactivity for advanced safety<br>assessment ahead of clinical trials<br>• Reduced immunogenicity risk<br>4 EngageTx<br>CD3 Antibody Panel |
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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>5 |
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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 mammalian<br>display CDR 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>6 |
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| 7<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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| 8<br>From Idea To Clinical Candidate: We Believe Our Discovery Platform<br>Improves Probability of Success, Speed, and Developability<br>AI-powered sequence<br>optimization to<br>improve performance<br>AI-powered precision<br>targeting of<br>conformational &<br>sub-dominant epitopes<br>Epitope-specific<br>antigens built to<br>efficiently & selectively<br>discover antibodies<br>AI-generated naïve<br>antibody library, free<br>of sequence liabilities<br>Optimized bi-specifics<br>leveraging broad<br>potency range, human-monkey cross-reactivity,<br>& sequence diversity<br>Optimized Leads<br>evaluated & ranked<br>in translational<br>disease models<br>Epitope Engineering Proprietary Human<br>mAb Library<br>StableHu Antibody<br>Optimizer EngageTx Engineered<br>Epitope<br>Optimized mAb<br>Lead Pool<br>Getting it right from the outset<br>Precision antibody targeting takes<br>the lengthy trial and error out of<br>mAb discovery and improves<br>probability of success<br>More speed, mitigated risk<br>Reduced number of iterative<br>optimization steps, lower<br>immunogenicity risk and<br>improved developability<br>Enhanced bispecifics control<br>Wide potency range with<br>reduced cytokine release and<br>NHP cross-reactivity to strengthen<br>preclinical safety assessment |
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| Capitalizing on AI: We Believe Our Platform Powers a Focused, Capital<br>Efficient Business Plan<br>9<br>AI Discovery<br>Platform<br>• Partner existing molecules or discovery<br>projects against new targets<br>• Potential for upfront, milestone<br>payments and/or royalties<br>Strategic<br>Partnerships<br>• Advancing a select few “fast<br>followers”<br>• Potential licensing and asset sales for<br>other molecules<br>Proprietary<br>Pipeline<br>• Exclusive licensing for non-core<br>therapeutic areas to 3rd parties<br>(vaccines, etc.)<br>• Potential for upfront technology<br>access fee and milestones plus<br>royalties for multiple targets<br>Third Party<br>Collaboration |
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| PROGRAMS EARLY DISCOVERY LATE DISCOVERY LEAD<br>OPTIMIZATION IND-ENABLING CLINICAL<br>Oncology<br>IBIO-101<br>Trop-2 x CD3*<br>MUC16<br>Target 5<br>EGFRvIII<br>CCR8<br>Target 8<br>Autoimmune PD-1<br>10<br>Catalyzing Innovation: Technology Stack Spurs Rapid Pipeline Growth and<br>Maturation in Cancer Immunotherapies<br>Immuno-Oncology<br>Immuno-Oncology<br>Immuno-Oncology<br>Immuno-Oncology<br>Immuno-Oncology<br>Immuno-Oncology<br>Autoimmune Diseases<br>Solid Tumors<br>*Developed with Engage Tx bispecific platform |
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| * Acquisition / Merger + License or collaboration 11<br>Market-Tested Potential: Competitor Early-Stage Deals Signal Promising<br>Opportunities for Our Pipeline<br>FEB 2021<br>Pre-2019 2020 2021 2022<br>CCR8<br>Gilead / Jounce+:<br>$85M upfront,<br>$35M equity investment,<br>$685M milestones<br>SEP 2020<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>IBIO-101 (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,<br>$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,<br>$130M milestones<br>OCT 2022<br>CD3<br>Gilead / MacroGenics+:<br>$60M upfront,<br>$1.7B milestones<br>JUL 2021<br>CD3<br>Eli Lilly / Merus+:<br>$40M cash upfront,<br>$20M investment,<br>$540M milestones<br>JUL 2021<br>CD3<br>Amgen / Teneobio*:<br>$900M upfront,<br>$1.6B milestones<br>2023<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<br>in 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<br>deferred),<br>$5B milestones<br>JUL 2020<br>APR 2023<br>EGFRvIII<br>Pierre Fabre / Scorpion+:<br>$65M upfront,<br>$553M milestones |
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| 12<br>iBio Company Highlights<br>• Ticker: IBIO (NYSE A); ~27.6M shares outstanding as of 6/30/23<br>• Reduced costs by ~67% post CDMO divestment from FY 23 Q1 to Q4<br>• Significantly reduced debt upon consummation of facility sale<br>Financial<br>AI-driven discovery<br>tech stack<br>• Patented epitope-engineering technology<br>• StableHu antibody optimizer coupled with mammalian display<br>• EngageTx next generation bi-specific antibody platform<br>Layered<br>Business Model<br>• Strategic partnerships<br>• Proprietary pipeline<br>• Exclusive platform licensing for specific disease areas outside of I/O<br>Pipeline of difficult<br>to find biologics<br>• Pipeline of 8 preclinical programs of 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 data for lead asset IBIO-101 |
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| Preclinical Pipeline<br>13 |
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| 14<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 15<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 16<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<br>Proliferation<br>-101<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>17<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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| 18<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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| 19<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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| 20<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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| 21<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>22<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 23<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 24<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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| 25<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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| 26<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 preclininical 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>27<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 28<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 29<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 30<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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| 31<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>32<br>EGFRvIII 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>33<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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| 34<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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| 35<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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| 36<br>Anti-MUC16 Tumor Associated Epitope<br>Non-Shed Epitope Anti-MUC16 Antibody |
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| +Regeneron MUC16xCD3<br>(Sept 2022):<br>Ph. 1 31% ORR<br>Ph. 2 enrollment<br>37<br>MUC16 Potential 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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| 38<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>39<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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| 40<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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| 41<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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| 42<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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| 43<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>44<br>Trop-2 x CD3 Bi-Specific Antibody for Head & Neck and Others 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>45<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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| 46<br>iBio’s Trop-2 x CD3 Bi-Specific Antibody Potently Kills Tumor Cells with Low<br>Cytokine Release<br>46<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 |
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| 47<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 |
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| 48<br>PD-1 Agonist<br>Supports Restoration of Homeostasis for Inflammatory<br>Diseases |
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| 49<br>PD-1 Agonist to Alleviate Inflammatory Disease<br>Selectively agonize<br>PD-1 without<br>antagonizing the<br>natural PD-1:PD-L1<br>anti-inflammatory<br>interaction<br>• Rheumatoid arthritis<br>• Broad application in treating<br>inflammatory disease<br>Target mechanism Potential indications Differentiation / opportunity<br>Recent Transactions & Milestones<br>• Potent PD-1 agonism vs.<br>benchmarks with in vitro<br>reporter and primary cell<br>assays<br>**Gilead / Mirobio (Aug 2022):<br>Acquired for $405M<br>*Merck / Pandion (Feb 2021):<br>Acquired for $1.85B<br>PRECLINICAL TESTING IND CLINICAL TESTING CLINICAL PROOF OF CONCEPT<br>Eli Lilly (May 2023):<br>Positive Ph 2a efficacy<br>in RA patients<br>• 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.<br>** 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. |
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| PD-1 PD-L1<br>TCR MHC<br>T-cell<br>Antigen<br>presenting<br>cell<br>50<br>Antagonizing PD-1 with PD-L1 Blocking Worsens Autoimmunity and Systemic<br>Inflammation Inflammatory Disease Tissue Healthy Tissue<br>Increased &<br>systemic<br>inflammation<br>No<br>T-cell<br>inhibition<br>No<br>T-cell<br>inhibition<br>Worsened<br>Strong<br>T-cell<br>inhibition<br>Weak<br>T-cell<br>inhibition<br>Autoimmunity<br>PD-1<br>Antagonist<br>Antibody |
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| 51<br>Agonizing PD-1 Without Blocking PD-L1 Restores Activated T-Cell<br>Suppression<br>Diseased Tissue<br>Reduced<br>inflammation<br>Healthy Tissue<br>Low-inflammation<br>preserved<br>PD-1 PD-L1<br>Strong TCR MHC<br>T-cell<br>inhibition<br>T-cell<br>Inflammatory<br>Disease Tissue<br>Healthy<br>Tissue<br>Weak<br>T-cell<br>inhibition<br>Strong<br>T-cell<br>inhibition<br>Strong<br>T-cell<br>inhibition<br>Improved<br>Autoimmunity<br>Antigen<br>presenting<br>cell<br>PD-1<br>Agonist<br>Antibody |
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| Benchmark<br>Antibodies<br>PD-1 Agonist Antibodies<br>52<br>In vitro PD-1 Agonism Equals or Surpasses Benchmarks and PD-L1<br>Ab ID EC50<br>(nM)<br>SD-671823 0.88<br>SD-300670 0.31<br>SD-030629 0.36<br>SD-136366 0.28<br>SD-759028 0.52<br>SD-313018 (bispecific) 0.30<br>AnaptysBio<br>APE12095 17.4<br>BMS/Celgene<br>PD1AB6 0.76<br>IgG1 isotype control inactive<br>SD-671823 SD-300670 SD-030629<br>SD-136366 SD-759028 SD-313018 (bispecific)<br>AnaptysBio APE12095 BMS/Celgene PD1AB6 IgG1 isotype control<br>Tetravalent<br>Bivalent<br>x<br>x<br>Data on file |
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| Data on file 53<br>Primary T-Cell Suppression Equals or Surpasses Benchmarks and PD-L1<br>IL-2 at 24 hrs.<br>% IL-2 Release<br>Mean of<br>6 donors<br>0<br>100<br>200<br>Anti-HEL IgG1<br>Isotype Control<br>CD69 at 72 hrs.<br>CD69 MFI<br>Mean of<br>6 donors<br>0<br>100<br>200<br>300<br>Anti-HEL IgG1<br>Isotype Control<br>iBio Molecules Benchmark Molecules Natural Agonist |
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