About iBio

iBio, Inc. (iBio) operates as a preclinical stage biotechnology company that leverages the power of Artificial Intelligence (AI) for the development of precision antibodies. The company's proprietary technology stack is designed to minimize downstream development risks by employing AI-guided epitope-steering and monoclonal antibody (mAb) optimization. In September 2022, iBio made a strategic pivot by acquiring substantially all of the assets of RubrYc Therapeutics, Inc. (RubrYc). This acquisition commenced the company's transition to an AI-enabled biotech company and led to the divestiture of its Contract Development and Manufacturing Organization (CDMO) business. This strategic decision allowed the company to focus resources on the development of AI-powered precision antibodies, positioning iBio at the forefront of this exciting field. One of the key features of iBio's technology stack is the patented epitope-steering AI-engine. This advanced technology allows the company to target specific regions of proteins with precision enabling the creation of antibodies highly specific to therapeutically relevant regions within large target proteins, potentially improving their efficacy and safety profile. Another integral part of iBio's technology stack is the machine learning (ML) based antibody-optimizing StableHu technology. When coupled with the company's mammalian display technology, StableHu has been shown to accelerate the Lead Optimization process. iBio also developed the EngageTx platform, which provides an optimized next-generation CD3 T-cell engager antibody panel. This panel is characterized by a wide spectrum of potencies, Non-Human Primate (NHP) cross-reactivity, enhanced humanness of the antibodies, and a maintained tumor cell killing capacity, all while reducing cytokine release. These attributes are meticulously designed to fine-tune the efficacy, safety, and tolerability of the company's antibody products. By incorporating EngageTx into iBio's own development initiatives, the company's internal pre-clinical pipeline reaps the benefits of the same cutting-edge technology extended to its potential partners. Artificial Intelligence in Antibody Discovery and Development The potential of AI in antibody discovery is immense and is being increasingly recognized in the biopharmaceutical industry. The mAbs market has seen impressive growth in recent years, with mAbs increasingly the top-selling drugs in the United States. This success has driven the industry to seek innovative methods for refining and improving their antibody pipelines. AI and deep learning, which have already revolutionized small molecule drug design, are now making significant strides in the development and optimization of antibodies. iBio is leveraging the company's AI-powered technology stack to enhance the success rate of identifying antibodies for challenging target proteins, expedite the process of antibody optimization, improve developability, and engineer finely calibrated bi-specifics. By continually refining the company's AI algorithms, incorporating new data sources, and developing robust experimental validation processes, iBio is paving the way for groundbreaking advancements in antibody design and drug discovery. Strategy The key elements of the company's strategy are to elevate epitope discovery, leverage its platform and pipeline by forming strategic partnerships, develop and advance its in-house programs cost effectively, tech license in diverse therapeutic areas, and focus investment in advancing the platform. AI-Technology Platform iBio's technology stack is a multi-layered, AI-powered system designed to significantly enhance the probability of success to discover and develop antibodies against hard-to-drug pathophysiologically relevant proteins. This platform comprises four key components, each playing a crucial role in the discovery and optimization of precision antibodies. The first layer, epitope engineering, leverages the patented AI-engine to target specific regions of proteins, allowing the company to engineer antibodies with high specificity and efficacy. The second layer involves the proprietary antibody library, which is built on clinically validated frameworks and offers a rich diversity of human antibodies. The third layer of the technology stack is the antibody optimizing StableHu AI technology, coupled with mammalian display technology. This combination speeds up the Lead Optimization process and potentially minimizes downstream risks, with the goal of making the overall development process more efficient and cost-effective. Finally, the company's EngageTx platform forms the fourth layer. It provides an optimized next-generation CD3 T-cell engager antibody panel characterized by a wide range of potencies, Non-Human Primate (NHP) cross-reactivity, increased humanness of the antibodies, and retained tumor cell killing capacity with reduced cytokine release. Each layer of the tech stack is designed to work synergistically, enabling the company to rapidly advance antibodies from concept to in vivo proof-of-concept (POC). AI Epitope Steering Technology iBio's Epitope steering technology is designed to address these issues by guiding antibodies exclusively against the desired regions of the target protein. By focusing on these specific regions, the company can overcome the limitations of traditional methods and significantly improve the efficiency and effectiveness of its antibody discovery process. iBio's AI engine creates engineered epitopes, which are small embodiments of epitopes on the target protein. The engine is trained to match the epitope structure as closely as possible and refine the designs for greater stability and water solubility, which are critically important factors. The optimized engineered epitope is then used to identify antibodies from naïve or immunized libraries. Naïve Human Antibody Library The fully human antibody library is built upon clinically validated, entirely human antibody frameworks. By leveraging public databases, iBio has extracted a diverse array of Complementarity-Determining Region (CDR) sequences. Subsequently, iBio has meticulously eliminated a range of sequence liabilities. Such careful curation process could potentially significantly reduce the development risk for antibodies identified from the company's library. StableHu AI Antibody-Optimizing Technology Antibody optimization is a pivotal step in the development of therapeutic antibodies. It refines an antibody's properties to enhance its efficacy, safety, and manufacturability. This process includes humanization, which alters non-human antibodies to mimic human antibodies, thereby reducing the risk of immune reactions when used in therapy. The proprietary StableHu technology is instrumental in this optimization process. StableHu is an AI-powered tool designed to predict a library of antibodies with fully human CDR variants based on an input antibody. This input can range from an early, unoptimized molecule to an approved drug. The model has been trained utilizing a set of over 1 billion human antibodies, progressively masking known amino acids within CDRs until the algorithm could predict the correct human sequence. While phage display libraries are often used in antibody optimization due to their vast diversity, they can increase developability risks, such as low expression, instability, or aggregation of antibodies. Mammalian display libraries, on the other hand, offer significantly improved developability but reduced diversity due to the smaller library size they can handle. StableHu overcomes this limitation by utilizing a machine learning algorithm generating focused library diversity within the capacity of mammalian display. Mammalian display is a technology that presents antibodies on the surface of mammalian cells, allowing for the direct screening and selection of antibodies in a mammalian cell environment. This approach is advantageous as antibodies that express well on the mammalian cells used in the display are more likely to express well in the production cell line. Moreover, single-cell sorting of antibody-displaying cells allows rapid selection of desired antibodies based on multiple dimensions, such as potency, selectivity, and cross-species selectivity. When paired with mammalian display technology, StableHu enables antibody optimization with fewer iterative optimization steps, lower immunogenicity risk, and improved developability. EngageTx CD3-Based T-Cell Engager Panel CD3-based T-cell engagers potentially offer significant clinical benefits in cancer treatment. They have the potential to effectively target and eliminate a wide range of tumor types, including those resistant to other therapies. By recruiting and activating the body's own T-cells to specifically target cancer cells, they can overcome some mechanisms of immune evasion, potentially leading to improved patient outcomes. However, first-generation T-cell engaging bispecific antibodies often face challenges related to safety and efficacy. They can cause severe side effects, such as cytokine release syndrome due to overactivation of the immune system. To address these issues, iBio used antibodies from an epitope steering campaign, as well as a first-generation T-cell engager as input and utilized the company's StableHu technology to identify a next-generation CD3 antibody panel. The sequence diversity generated by StableHu led to an antibody panel with a wide range of potencies, which allows the company to pair the panel with a wide variety of tumor-targeting antibodies. Importantly, iBio was able to retain T-cell activation and tumor cell killing capacity with significantly reduced cytokine release. Furthermore, the company's StableHu technology enabled it to engineer NHP cross-reactivity into EngageTx. This allows for advanced safety assessment in NHP ahead of clinical trials, providing another layer of safety assurance. Pre-Clinical Pipeline iBio is in the process of building and advancing its preclinical pipeline. The focus of this pipeline is primarily on immuno-oncology, with one program also dedicated to the immunology space. By leveraging iBio's technology stack, the pipeline is geared towards hard-to-drug targets and molecules offering differentiation. To mitigate target risk and capitalize on the learnings of competitors, iBio's programs are primarily adopting a fast follower strategy. This approach allows iBio to focus on targets that have to some extent been validated and learn from the advancements of those ahead in the field. Therapeutics Immuno-Oncology The company has established its own AI drug discovery and drug development capabilities in San Diego, California, has built a pipeline of nine immuno-oncology programs. IBIO-101 The company has a worldwide exclusive licensing agreement with RubrYc to develop and commercialize RTX-003 (now referred to as IBIO-101), an anti-CD25 monoclonal antibody [mAb]. In September 2022, the company acquired exclusive ownership rights to IBIO-101. IBIO-101 is a second-generation anti-CD25 mAb that has demonstrated in preclinical models of disease the ability to bind and deplete immunosuppressive regulatory T [Treg] cells to inhibit the growth of solid tumors. In vitro characterization of IBIO-101 demonstrated potent binding to recombinant CD25 while preserving IL-2 signaling. Further assessment of IBIO-101 showed selective Treg depletion and sparing of Teffs. In a humanized mouse disease model, IBIO-101, when used as a monotherapy, effectively demonstrated its mechanism of action by significantly enhancing the Treg/Teff ratio, resulting in the suppression of tumor growth. When paired with an anti-PD-1 checkpoint inhibitor in the same model, the combined treatment of IBIO-101 and anti-PD-1 exhibited superior tumor inhibition compared to either anti-PD-1 or IBIO-101 used independently. iBio has progressed IBIO-101 to the IND-enabling phase and entrusted its Chemistry, Manufacturing, and Controls (CMC) development to a reputable Contract Research Organization (CRO). In the initial stages of this process, IBIO-101 has exhibited promising attributes for CMC progression. Notably, the company has pinpointed optimal cell lines for master cell bank creation and has set in place a CMC methodology to produce IBIO-101 in compliance with current Good Manufacturing Practice (cGMP) standards. The company continues to advance its IL-2 sparing anti-CD25 antibody, IBIO-101, and anticipates moving the program from IND-enabling stage to an IND filing during the calendar year 2025. TROP-2 x CD3 Bispecific iBio has identified highly potent, fully human TROP-2 (Trophoblast Cell Surface Antigen 2) monoclonal antibodies, which have been formatted into bispecific TROP-2 x CD3 molecules using the company's T-cell engager antibody panel, EngageTx. TROP-2 is highly expressed in multiple solid tumors, including breast, lung, colorectal, and pancreatic cancers and is closely linked to metastasis and tumor growth. TROP-2 antibody drug conjugates have been developed to deliver toxic payloads to these cancer cells but could risk harming healthy cells and cause adverse effects. The Company's bispecific approach has the potential to increase the therapeutic window, while promoting a robust and long-lasting anti-tumor response. Combining the bispecific TROP-2 approach with immunotherapies like checkpoint inhibitors can potentially lead to improved clinical outcomes. Using EngageTx, iBio's lead TROP-2 x CD3 bispecific antibody was engineered to potently kill tumor cells while limiting the release of cytokines, like Interferon Gamma (IFNg), Interleukin 2 (IL-2) and Tumor Necrosis Factor Alpha (TNFa), all of which have the potential to cause cytokine release syndrome. When compared to a bispecific molecule engineered with iBio's TROP-2 binding arm and a first generation CD3 engager, SP34, the company's lead TROP-2 x CD3 bispecific antibody showed a markedly reduced cytokine release profile, potentially indicating a decreased risk for cytokine release syndrome. When tested in a humanized mouse model of squamous cell carcinoma, iBio's lead TROP-2 x CD3 bi-specific antibody demonstrated a significant 36 percent reduction in tumor size within just 14 days after tumor implantation, and after only a single dose. MUC16 MUC16 is a well-known cancer target often overexpressed in several types of solid tumors, including ovarian, lung, and pancreas cancers. Specifically, MUC16 is a large extracellular protein expressed on more than 80% of ovarian tumors. Tumor cells can evade immune attack by shedding or glycosylating MUC16, making it difficult for traditional antibody therapies to effectively target and destroy the cancer cells. Using the company's patented epitope steering AI platform, iBio's innovative approach to this challenge allows its new mAbs to bind to a specific region of MUC16 that is not shed or glycosylated, circumventing both tumor evasion mechanisms and potentially providing a powerful tool in the fight against cancer. During its immunization and screening campaign, iBio identified several hits that specifically bound to the non-shed region of MUC16 while no binding to the shed fragment of MUC16 was observed. During pre-clinical studies, iBio's MUC16 molecule has demonstrated binding to MUC16 on OVCAR-3 ovarian cancer cells as shown below. After engineering the leading MUC16 molecule with a fully human framework, the MUC16 molecule retained potent binding to the engineered epitope and maintained binding to human OVCAR-3 ovarian cancer cells. EGFRvIII EGFRvIII is a specific variant of the EGFR protein, unique to tumor cells. Unlike the more common EGFR, EGFRvIII is not found in healthy cells, making it an attractive target for therapeutic interventions. This variant is most prominently associated with glioblastoma, a type of brain cancer and head and neck cancer, but can also be present in certain cases of breast, lung, and ovarian cancers, among others. In the company's pursuit of innovative treatments, iBio is exploring antibody therapeutics that specifically target EGFRvIII, aiming to address these cancer types without affecting healthy cells. Leveraging the company's patented AI-enabled epitope steering engine, it has specifically directed antibodies to target a unique epitope found exclusively on EGFRvIII, and not on the wildtype receptor, EGFR. Through this precision approach, iBio has designed tumor-specific molecules aimed at selectively targeting cancer cells while preserving healthy ones, potentially offering patients a more focused and safer therapeutic solution. iBio's hit molecules have demonstrated strong binding to the tumor-specific EGFRvIII protein without targeting the wildtype EGFR. Additionally, these molecules have effectively eliminated tumor cells, while sparing healthy ones, in in vitro cell killing tests. iBio's lead anti-EGFRvIII antibody was specially engineered to enhance its ability to attack cancer cells and has proven effective in a mouse model for head and neck cancer. In preclinical studies, iBio's anti-EGFRvIII antibody demonstrated a 43 percent reduction in tumor growth compared to untreated animals. CCR8 Using its unique AI-driven technology, iBio successfully identified molecules targeting CCR8, addressing some of the hurdles often faced when creating therapies that target GPCR with antibodies. iBio's specialized anti-CCR8 antibody has shown strong attachment to cells expressing CCR8 and effectively disrupted the CCR8 signaling process, resulting in the efficient elimination of Tregs derived from primary human immune cells. Notably, iBio's CCR8-focused molecule did not attach to cells overproducing CCR4, highlighting its precision in targeting only CCR8. iBio's CCR8 antibody has proven effective in a mouse model for colon cancer. Preclinical studies show iBio's anti-CCR8 molecule inhibited tumor growth and achieved a 22 percent reduction in tumor size compared to its pre-treatment dimensions. iBio specifically engineered the anti-CCR8 molecule as a high Antibody-Dependent Cellular Cytotoxicity (ADCC) antibody to enhance its ability to attack cancer cells. Autoimmune PD-1 Agonist iBio purchased the global rights to a partnership-ready PD-1 agonistic mAb intended to treat serious autoimmune disorders. While the goal in immuno-oncology is to remove immune tolerance towards cancer cells, in autoimmune diseases the opposite is the case, because autoimmune diseases can result from deficits in peripheral and/or central tolerance mechanisms which presents an opportunity for therapeutic intervention. Specifically, agonism or stimulation of inhibitory receptors like PD-1 or CTLA4, which mediate peripheral tolerance is a promising approach to treat autoimmune diseases. Unlike PD-1 antagonists used in immuno-oncology, PD-1 agonists are difficult to find. RubrYc used its AI Discovery Platform to discover PD-1. PD-1 is currently in the late-discovery stage, having undergone extensive screening and in vitro characterization, and the company anticipates it will be advanced into in vivo models as IBIO-102, in the near future. Furthermore, in preclinical studies, iBio's PD-1 agonists have been evaluated using a primary T-cell assay. The company's top-performing molecules showed a significant decrease in the proinflammatory cytokine IL-2 and reduced expression of the T-cell activation marker CD96. Both of these outcomes are indicative of the desired dampening of T-cell activation. iBio's PD-1 agonist is in the late-discovery stage and it anticipates it will be advanced into in vivo models as IBIO-102, in the near future. Fibrosis IBIO-100 As part of this decision, the company completed the pre-clinical cancer studies it was conducting in collaboration with University of Texas Southwestern using E4 endostatin peptide, which is derived from IBIO-100. After the conclusion of the pre-clinical studies, the company determined not to further pursue this oncology program. Suppliers The company outsources certain functions and supplies to third parties, such as Charles River Laboratories, Sartorius AG, Fisher Scientific, Lonza Sales AG, and Twist Bioscience Corporation. Strategic Alliances, Collaborations, and Joint Ventures iBio has formed collaborations and strategic alliances to gain access to funding, capabilities, technical resources and intellectual property to further its development efforts, commercialize its technology and to generate revenues, including through the use of its patented epitope-steering AI-engine and its EngageTX platform. National Institute of Allergy and Infectious Diseases In June 2023, iBio entered into a research collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), to investigate the potential of the patented AI-driven epitope steering platform for the development of a vaccine for Lassa fever, which there is no vaccine available. Based on the viral epitopes identified by researchers at NIAID's Vaccine Research Center (VRC), the company will work with the VRC to determine if using the platform to steer immunity toward these epitopes offers advantages over other vaccine development approaches. Intellectual Property The company owns 95 patents. Of the 95 patents, 24 are U.S. and 71 are international. Since July 1, 2022, the company has primarily focused its intellectual property estate on its preclinical assets filing 10 provisional patents in the U.S. and foreign countries, including for chemokine receptor 8 (CCR8) antibodies, epidermal growth factor receptor variant III (EGFRvIII) antibodies, anti-MUC16 antibodies, TROP2 antibodies, CD3 antibodies, and recently filed a provisional patent for its high-efficiency, conditionally-activated antibodies. The company has 18 U.S., 2 Patent Cooperation Treaty, and 32 international applications pending. International patents and applications include numerous foreign countries, including Australia, Brazil, Canada, China, Hong Kong, India, Japan, Korea, and several countries in Europe. In the U.S. the company's patents expire between 2023 and 2036. Outside the U.S. these patents expire between 2023 and 2036. The 8 patents expiring in 2023 in the U.S. and overseas are related to virus-induced gene silencing in plants. Included in the 95 patents are 30 U.S. and foreign applications that the company acquired from RubrYc for novel antibodies, scaffold technology, and a machine learning apparatus for engineering meso-scale peptides, including 1 allowed application. As part of the plant portfolio, the company exclusively owns the right to use certain intellectual property acquired by or developed at Fraunhofer for human health and certain veterinary and diagnostic applications. The company also owns intellectual property developed or acquired independently of Fraunhofer as part of the plant portfolio. The technology and products covered by the company's issued and pending patent applications are summarized below: Technology and Product Patents (the U.S.) includes virus-induced gene silencing in plants; transient expression of foreign genes in plants; production of foreign nucleic acids and polypeptides in sprout systems; production of pharmaceutically active proteins in sprouted seedlings; systems and method for clonal expression in plants; recombinant carrier molecule for expression, delivery and purification of target polypeptides; influenza antigens, vaccine compositions, and related methods; plague antigens, vaccine compositions, and related methods; influenza therapeutic antibodies; trypanosomiasis vaccine; anthrax antigens, vaccine compositions, and related methods; and use of endostatin peptides for the treatment of fibrosis. Pending Technology Patent Applications (the U.S. and International) includes activation of transgenes in plants by viral vectors; transient expression of proteins in plants; thermostable carrier molecule; in vivo deglycosylation of recombinant proteins in plants; scaffold technology; machine learning apparatus for engineering meso-scale peptides; and methods of making conditionally-activated antibodies. Pending Product Patent Applications (the U.S. and International) includes antibodies, influenza vaccines, influenza therapeutic antibodies, anthrax vaccines, plague vaccines, HPV vaccines, trypanosomiasis vaccine, vaccines, COVID-19 vaccines, antibodies against chemokine receptor 8 (CCR8), antibodies against epidermal growth factor receptor variant III (EGFRvIII), antibodies against MUC16, antibodies against TROP2, antibodies against CD3, and high efficiency and conditionally activated antibodies. Competition The company's most significant competitors, among others, are fully integrated pharmaceutical companies, such as Eli Lilly and Company; Bristol-Myers Squibb Company; Merck & Co., Inc.; Novartis AG; MedImmune, LLC (a wholly owned subsidiary of AstraZeneca plc); Johnson & Johnson; Pfizer Inc.; Merck KGaA; and Sanofi SA. The company also competes with more established biotechnology companies, such as Genentech, Inc. (a member of the Roche Group); Amgen Inc.; Gilead Sciences, Inc.; and its subsidiary Kite Pharma, Inc. The company competes with cancer immunotherapy companies, such as Bluebird Bio, Inc.; Transgene SA; Bausch Health Companies; Lumos Pharma; Agenus Inc.; Aduro Biotech, Inc.; Advaxis, Inc.; ImmunoCellular Therapeutics, Ltd.; IMV Inc.; Oxford BioMedica plc; Bavarian Nordic A/S; and Celldex Therapeutics, Inc., as well as tech enabled drug discovery companies, such as Recursion; Abcellera Biologics, Inc.; Cellarity; and BenevolentAI. Research and Development (R&D) For the year ended June 30, 2023, the company's R&D expenses were approximately $10.3 million. Discontinued Operations As of June 30, 2023, iBio contract development and manufacturing organization's operations are discontinued. History iBio, Inc. was incorporated under the laws of the state of Delaware in 2008.