What is iBio?
iBio (NYSE MKT:IBIO) develops and offers product applications of its iBio Technology platform, providing collaborators full support for turn-key implementation of its technology for both proprietary and biosimilar products. The iBio Technology platform is a proprietary, transformative technology for the development and production of biologics using transient gene expression in unmodified green plants. The technology has been validated in both preclinical and clinical studies, with interim positive results from a Phase 1 clinical trial of an iBio Technology platform-produced H1N1 Influenza Vaccine. iBio is actively engaged in a strategy to commercially license the iBio Technology platform across multiple markets and geographic regions to provide various revenue streams. Further information is available at: www.ibioinc.com.
What is the iBio Technology platform?
iBio Technology is a new method for the production of biotherapeutics and subunit vaccines in whole plants, bypassing expensive and complicated cell culture systems. The proprietary iBio Technology vector system utilizes the ability to efficiently introduce non-integrating foreign DNA into a plant cell nucleus by Agrobacterium plasmids to launch virus-based mRNA replication that takes over the plant cell's protein synthesis to produce any desired protein. The hybrid Agrobacterium/viral gene system does not permanently alter the plant's genetic makeup; it is not transgenic and does not result in the production of plant virus particles. Transfer of the iBio Technology vector to every cell in every leaf of the plant is near simultaneous, and within four to seven days the desired protein accumulates transiently in the plant leaves, where it can be easily harvested for purification. Unlike cell culture systems, the iBio Technology platform can be in production within weeks and does not require the time-consuming identification and isolation of high-producing cell clones which need to be scaled up for manufacturing. Additionally, the plants are grown in a soil-free, hydroponic medium under strict climatic and lighting controls for the highest degrees of reproducibility. No animal derived products or growth factors are utilized, eliminating the risk of human pathogens being introduced in the manufacturing process, and the expensive aseptic liquid handling process steps for cell culture are not required. The iBio Technology has been validated through the construction of a cGMP manufacturing facility that has provided clinical trial material for multiple FDA-approved studies.
What products can be made with the iBio Technology platform?
The iBio Technology platform has a wide range of commercial capability. Various proteins have been successfully produced with the iBio Technology platform and demonstrated, through preclinical and clinical studies, to be safe, efficacious, and to have anticipated biological functionality. These proteins include antibodies, interferons and cytokines, growth factors, protease inhibitors, clotting factors and enzymes for replacement therapy (Alpha-Galactosidase A). In addition, a variety of antigens for vaccines against diseases such as influenza, anthrax, malaria, sleeping sickness, plague and human papilloma virus have been produced, as well as several therapeutic antibodies for the treatment of acute treatment of influenza and anthrax infections. Virtually any protein that can be produced in prokaryotic or other eukaryotic expression systems can be made in plants with the iBio Technology platform with significant cost and pricing advantages.
Where did iBio get its technology?
iBio is currently developing CFB03, a protein derived from endostatin with demonstrated antifibrotic effects. CFB03 is produced using iBio's proprietary plant manufactured protein technology, and has been shown to arrest and reverse fibrotic disease in skin and lungs of preclinical models in both mice and human tissue. CFB03 is in a preclinical research phase, and is being developed initially for the treatment of diffuse systemic scleroderma.
Will iBio develop its own products?
iBio's investments to date have focused primarily on the development and application of its iBio Technology platform product. As iBio builds its revenue base through commercial alliances for the use of its platform technology, it may choose to invest in early-stage clinical development from the best of the preclinical product targets. The objective of the additional investment is to enhance the value prior to forming alliances with other companies for final development and marketing.
Since biotechnology products have been successfully produced for so many years, why is iBio Technology important now?
The iBio Technology platform has been validated in both preclinical and clinical studies, as well as vetted by multiple government and non-government organizations. Through these processes, iBio's technology has demonstrated qualities that present numerous advantages over previous methods of manufacturing biotechnology products as measured by time, cost, flexibility, and yield. These advantages are likely to radically alter the way these important but expensive biological products are produced. Compared to existing technologies, a manufacturing facility based on the iBio Technology platform requires less capital infrastructure and has lower operating costs because expensive bioreactors and aseptic liquid handling technology is not required to generate production biomass. The scalability and "simplicity" of the platform allow for modular growth and the ability to produce multiple products at a single facility. Using the iBio Technology platform, production cycles are reduced to days versus months for competitive processes. Since the platform contains no human or animal pathogens, the safety profile of platform products is more attractive. Finally, nearly unlimited surge capacity offers rapid response to pandemic disease threats or bioterrorism events.
What are the advantages of iBio technology for making biologics?
The key advantages of the iBio Technology are speed, simplicity, flexibility and lower cost. Unlike more conventional systems that fundamentally alter a host cell's DNA, there is no need to isolate and expand rare, high-producing cell clones to production level. A gene of interest can be cloned and inserted into the iBio Technology vectors and be ready for production at scale within a month's time. The transient nature of this powerful expression system allows the accumulation of massive amounts of desired protein over a four- to seven-day period when purification can then begin. The simplicity of the iBio Technology comes from the use of whole plants for the manufacturing of protein. These plants can be grown in chemically-defined medium in the open air or climate-controlled greenhouse, and do not require the expensive aseptic culture systems required to prevent contamination of cell culture production methods. The system is highly flexible, allowing the expression of vaccine antigens, monoclonal antibodies, replacement enzymes, blood cell growth factors, and many other products that cannot be produced by more traditional expression systems. Finally, the low cost of raising whole plants to provide the biomass for manufacturing obviates the need for expensive bioreactors and medium, as well as the lengthy and resource-intensive product development efforts seen with traditional cell-culture manufacturing.
Have products made with the iBio Technology been tested in human clinical trials?
Yes. Human clinical trials of products made using the iBio Technology platform began in 2010 with the initiation of Phase 1 clinical trials of an H5 avian influenza vaccine sponsored by the Bill & Melinda Gates Foundation and a vaccine for H1N1 influenza sponsored by DARPA.
On June 2, 2011, iBio announced positive interim results from a Phase 1 clinical trial of an iBio Technology platform-produced subunit vaccine directed against Influenza A/California/04/09 (H1N1). The vaccine demonstrated a strong induction of dose correlated immune responses, with or without adjuvant, as assessed by virus neutralization assays and hemagglutination inhibition (HAI responses). The vaccine was safe and well tolerated at all doses when administered with and without adjuvant.
In addition to the two influenza vaccines that have completed Phase 1 studies, a transmission-blocking vaccine for malaria sponsored by the PATH Malaria Vaccine Initiative (MVI), a hookworm vaccine sponsored by the Sabin Vaccine Institute, and a vaccine to protect from anthrax conducted at the Walter Reed Army Institute of Research are currently in Phase 1 trials.
Why can iBio produce influenza vaccines faster than companies that use chicken eggs?
iBio's process is not dependent on being able to culture live viruses, to genetically engineer cell lines, or to produce large volumes of sterile starting material. Using the iBio Technology platform, a vaccine target can be produced in less than three weeks because the gene engineering process and the protein production processes are inherently faster than virus production in chicken eggs.
Why does iBio use green plants?
Plants carry out most of the same biochemical functions as human cells during protein synthesis and processing. iBio's technology provides a cost effective basis to use the ability of green plants to produce complex proteins ideally suited for human health applications.
Why is iBio Technology faster at producing than other plant-based protein companies?
iBio Technology is a third-generation plant-based protein expression technology. The first generation, which some companies still use, relies on the creation of transgenic plants with a foreign gene permanently incorporated into the plant's DNA. The second generation, still used by some companies, is based on transient virus-based infectious delivery of genes into non-transgenic plants. While this technology works rapidly, there are yield constraints and target product size limitations that limit its applicability. The iBio Technology harnesses the combined features of bacterial, viral and plant biology to achieve the speed of transient production without the yield and size limitations of older technology. Because iBio's technology is proprietary and protected by issued and pending patents, it is not available to companies using older or publicly available technology except through commercial agreements with iBio.
How is iBio's process less expensive than those used by other plant-based or mammalian cell-produced protein companies?
iBio's technology is more efficient than previous methods of manufacturing biotech products, as measured by time, cost, and yield, and is likely to radically alter the way these important but expensive products are produced. A manufacturing facility based on the iBio Technology platform requires substantially less capital for the same dose capacity as facilities dependent on cultured animal cells or the even older approach of using bacterial fermenters or chicken eggs. Unit manufacturing costs are significantly lower because the iBio Technology platform eliminates the need of expensive bioreactors. Additionally, iBio's technology includes proprietary features not available to companies using older or publicly available plant-based technologies. These features enhance the economic efficiency of the iBio Technology platform relative to others by providing higher yields and applicability to a broader range of products.
Is it safer to produce biologics with plants than with animal cells?
There are obvious contamination risks that exist with the current methods of producing proteins using animal cells in bioreactors. A good example of this type of contamination risk was demonstrated when a virus within a bioreactor shutdown production of a Genzyme facility in Allston, MA. The shutdown affected five Genzyme drugs used to treat rare genetic disorders, including two - Cerezyme and Fabrazyme - that were rationed due to short supply resulting from the facility shutdown. Animal viruses do not infect plants, relieving the risk of contamination of mammalian-based manufacturing systems.
Will there be problems obtaining FDA approval for pharmaceuticals made with plants?
The FDA is very familiar with the use of green plants to produce pharmaceutical proteins. In 2000, the FDA formed a working group with the USDA to provide a clear path for the use of plants in therapeutic protein and vaccine production. The FDA issued the draft Guidance for Industry: Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals in 2002 to set for guidelines on host plant selection, environmental considerations, process-related issues, and pre-clinical and clinical testing requirements. The approach the FDA takes to regulating vaccines and other biologics produced in plants is similar to their requirements for other methods of protein production in that product approval is dependent on the safety and efficacy of the product, and consistency and reliability of the production process.
Is there a risk with plants making human proteins incorrectly resulting in them not working for medical applications?
Plants properly synthesize virtually any protein a human cell can synthesize by carrying out the same biochemical steps, including correct signal sequence processing and proper protein folding and disulfide bridge formation. In some cases, glycosylation patterns may differ between plants and human cells, but these differences can be controlled and corrected if they are significant to the function of the product. Recent scientific publications have suggested that plant-manufactured antiviral antibodies.may be superior to those produced using mammalian cells due to enhanced killing of virus-infected cells.
Have pharmaceuticals or vaccines made in plants ever been tested in humans?
Yes. Human testing of products made using the iBio Technology platform began in 2010 with the initiation of phase 1 clinical trials of an H5 avian influenza vaccine sponsored by the Bill & Melinda Gates Foundation and a vaccine for H1N1 influenza sponsored by DARPA.
The first human test of a therapeutic protein made in plants was conducted by NeoRx Corporation in 1997. The product was NeoRx's experimental cancer therapeutic, Avicidin, which incorporated a monoclonal antibody produced in transgenic plants by a unit of Monsanto Co. Unfortunately, although there were no problems with the quality of the plant-made antibody itself, the Avicidin product was not successful. About the same time, Planet Biotechnology tested a transgenic plant-derived antibody for the prevention of tooth decay in collaboration with Guy's Hospital in London. Transgenic plants have since been used to produce several products that have entered human clinical trials, including gastric lipase, interferon and insulin. The most advanced product is human glucocerebrosidase, produced in transgenic carrot cells by Protalix. Phase 3 human clinical trials have been completed and Protalix has submitted data to the FDA in support of an application for marketing approval.
Viral vectors were used to produce proteins for individualized treatment of non-Hodgkin's lymphoma in a Phase 1 clinical trial conducted in 2002. The Icon Genetics unit of Bayer AG is currently conducting a Phase 1 clinical trial of individualized cancer therapy based on their transient expression technology for producing proteins in plants.
What is glycosylation and is it a problem?
Glycosylation is a natural process in yeast, plant, insect and mammalian cells whereby carbohydrate residues are added as side chains to a protein. Glycosylation can promote the correct folding of a protein into the three-dimensional structure required for the protein to function, and can also help the protein resist breakdown in the body. Glycosylation across species tends to have a common core structure, along with species-specific variations. In most cases, the common structure is sufficient to promote the correct folding of the protein, while the variations seen in different species serve to optimize the performance of the protein in that species. Plants are entirely able to add the common core structure, but cannot produce some of the variations seen with mammalian-produced glycoproteins without further manipulation of the plant system. However, these mammalian-specific modifications are, in most cases, not necessary for the proper function and bioactivity of a plant-manufactured protein; the abundant scientific literature in this area grows daily. Some of the mammalian-specific modifications can be useful in stabilizing the protein as it circulates in the bloodstream, but plant-derived proteins such as monoclonal antibodies have circulation half-lives comparable to mammalian produced versions. As a final consideration, the common mammalian expression systems come from rodent cells, which add rodent-specific sugars to proteins that have been shown to cause immune responses in patients receiving drugs manufactured in these systems.
What other technology is competitive with iBio's?
iBio's numerous advantages make it extremely competitive against traditional methods of producing biologics, such as animal cell bioreactors which are widely used by major pharmaceutical and biotechnology companies. Due to its scope of capability and cost structure, the iBio Technology platform offers advantages over the new technologies such as cultured insect cells, transgenic plant technology and competing whole plant transient technologies, which either lack IP protection or have limited product capabilities.
Does iBio produce the final active ingredient or vaccine antigens used in products?
iBio is primarily in the business of licensing its platform technology to third parties for use in their own product manufacturing. In cases in which iBio would manufacture for a client, it would produce pharmaceutical grade protein (active pharmaceutical ingredient [API] or vaccine antigens for formulation into the final product by the client.)
What is iBio's relationship with Fraunhofer? Who owns the technology?
iBio has worked with the Fraunhofer USA Center for Molecular Biotechnology (CMB) since 2003 and owns the IP and technology developed there, including the iBio Technology platform. iBio's commercial rights are worldwide and exclusive in the field of human health and include limited rights to veterinary applications. iBio granted CMB an exclusive, royalty-bearing license to the technology for use in other fields. Under the terms of an existing multiyear agreement, iBio continues to accrue ownership of new technology with exclusive rights in the human health field in exchange for ongoing research funding commitments to CMB.
What is iBio's relationship with the Bill & Melinda Gates Foundation?
iBio and Fraunhofer established a license agreement at the request of the Bill & Melinda Gates Foundation to address its interest in providing access to vaccines to the world's poorest countries through the Global Access to Vaccines Initiative (GAVI). Fraunhofer has received substantial funding from the Bill & Melinda Gates Foundation to support development of vaccine products using the iBio Technology.
The license to Fraunhofer is non-exclusive and non-royalty bearing, and limited solely to Global Health Vaccines, which are vaccines for human or veterinary use for the prevention of malaria, tuberculosis, rotavirus, trypanosomiasis, hookworm and rabies. The Agreement establishes iBio's technology as the preferred manufacturer of these vaccines and provides a right of first refusal to iBio to provide technology transfer for manufacturing services to achieve Global Access Objectives on a commercially reasonable, competitive and sustainable cost basis.
Under the terms of the Agreement, Fraunhofer will use the iBio Technology to develop and test new GAVI vaccines funded by the Bill & Melinda Gates Foundation. In accordance with prior agreements, iBio will own new technology and improvements to existing technology arising during the course of the program at no cost to its shareholders.
Does iBio have patents on its technology?
As of February 2016 iBio had 20 issued US patents, 44 issued international patents and many pending applications.