Had a look at the Eos website today after the PCOP purchase. Has recently been updated. Parking some of the interesting stuff below -
We approach the identification and validation of targets in a way distinct from traditional drug development programs. Our method begins by choosing a disease for which we can identify a key pathogenic cell (e.g. cancer and the cancer cell). We then examine both diseased and normal tissues to find all genes that are uniquely or preferentially active in the disease-causing cell. We call this process "specificity validation." We do this because we want our treatments to thoroughly attack those cells; i.e. to maximize efficacy, but do so without toxicity or other harm to all normal organs in the body. We convert select genes into proteins and assess their potential as "targets." Along the way, we use an integrated series of tools and technologies that include:
* Collections of all normal human tissues and also collections of tissues containing the specific diseases on which we focus. We do this in collaboration with world-class investigators who share our commitment to finding new treatments for the disease;
* Custom designed GeneChip® arrays that can assess the activity in those tissues of essentially all human genes. Since early 2001, we have been working with an Eos-designed, custom GeneChip® with virtually the entire human genome on one chip;
* Proprietary bioinformatics to identify disease-specific gene activity in a statistically rigorous manner;
* Antibody-generating tools, including mice and phage, to produce fully-human monoclonal antibodies;
* Tissue arrays that contain hundreds of tiny specimens of human pathological and normal tissues on single microscope slides; and
* Experimental model systems, both in vitro and in vivo, for probing the efficacy of chosen targets with antibodies.
The structure of a target and its location on or in the cell determines which kind of treatment, e.g. antibodies, small molecule drugs, or vaccines, is most likely to be effective. If a target meets our criteria of being both novel and highly specific for the disease-causing cell, i.e. if it is specificity validated, then we proceed further. We focus our efforts on targets that are best addressed by antibodies. Our criteria: targets that are abundantly present in disease cells and that antibodies can attack, but that are not present or accessible to antibodies anywhere else in the healthy human body. To ensure that other targets, better addressed by small molecules or vaccines, lead to treatments for patients, we have and will continue to form alliances with other leading biopharmaceutical companies.
The next step is to perform "efficacy validation", a series of overlapping studies to predict and confirm whether a drug made against that target will likely be useful for patients. We test our potential drug at this step in both hundreds of archived tissue samples and also in animal models. If the results are favorable, then we can take this same drug directly into clinical testing. This takes months to years off the traditional drug development timeline. Meanwhile, the information we get lets us weed out, at this early stage, drugs that are likely to be ineffective or toxic long before starting trials in people. We save time and money, while picking the best from among the many possible targets that we are discovering. When necessary, we add potent toxins to ensure that we kill the disease cell. By coupling these toxins to our antibodies, we aim to avoid the side effects that patients experience when given the toxin by itself (i.e. the side effects that are caused by many chemotherapy drugs on market today).
Eos has ongoing programs to identify and validate targets in angiogenesis and in breast, prostate, colorectal, and lung cancer. Eos is using the best of these targets to rapidly and aggresively bring forward treatments for these diseases.
Human Pathologic Tissue Collection
Our tissue acquisition programs are executed in collaboration with premier universities and medical research institutions throughout the world. Each specimen has patient history and is Internal Review Board (IRB) approved.
These programs, in the area of cancer, are designed together with the participating institution to include four major components: i) collection of frozen specimens of dissected primary cancers along with samples of matched normal tissue; ii) acquisition of copies of the pathology reports accompanying each tumor; iii) clinical follow-up data obtained by periodic chart reviews and by the Cancer Center Tumor Registry, indicating for each of these cancers whether patients developed or remained free of tumor metastases; iv) retrospective samples for construction of tissue arrays allowing independent validation of target molecules.
In addition to producing these primary archives, our collaborating pathologists identify and retrieve tumor blocks from a second distinct set of cancer cases. Generally these cases are from individuals for whom five year clinical follow-up after cancer diagnosis is available, which we employ as an independent "secondary" or validation set of cancer cases using tissue array technology.
To date, we have profiled the following tissue samples:
* Breast cancer (primary tumor & liver metastatic samples) > 70 samples
* Colorectal cancer (primary tumor & liver metastatic samples) > 70 samples
* Prostate cancer > 50 samples
* Lung cancer > 40 samples
* Ovarian cancer > 40 samples
* Rheumatoid arthritis database > 30 samples acquired via mini-arthroscopy during the progression of disease
* For bladder, cervical, uterine, renal and gastric cancers, tissues have been secured and profiling is underway.
Human normal tissue atlas
Eos has carefully acquired IRB approved normal human tissues and cell types as part of an organ transplant program with a major university medical center. These samples create an internal reference database of gene expression to which we compare data from pathological specimens. Currently we have profiled over 145 normal human tissue and cell samples covering > 50 different tissues.
Eos Custom-Designed Affymetrix GeneChip®
We have designed proprietary arrays in the following formats:
Eos Hu01 and Eos Hu02:
* These two arrays together contain probes to detect the activities of 80% of all human genes;
* They are fully quality-controlled and validated, and we are actively pursuing lead targets from our biological interrogations using these arrays.
Eos Hu03:
* This is our most advanced array design;
* It contains on a single array probes to detect the activities of ~59,000 genes, or essentially all of the human genes identifiable in the complete human genome.
We anticipate fully deploying our Hu03 GeneChip array by the first quarter of 2001.
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Bioinformatics
Eos has developed its own proprietary suite of highly parallel bioinformatics tools, specially-designed to analyze data of the magnitude of the human genome. A key element to the success of these bioinformatics tools is that we have created them for our own use, not as a product offering. Furthermore, we use them during the actual stream of data flow, not as an isolated step after-the-fact (as is the case with many commercially available software packages). Eos gene expression analysis tools include:
* A proprietary tool for DNA microarray normalization. Eos has developed a novel calibration method for comparing gene expression data from numerous and diverse experimental data sets.
* Eosurveyor™, a unique gene expression analysis tool for statistical mining of DNA microarray data. Gene expression data may now be evaluated with statistical confidence that a gene is changing during a disease process, minimizing false negative as well as false positive results. Eosurveyor™ was created to take full advantage of increasing volumes of independent samples within an expression database, going far beyond pair-wise comparison.
* An automated quality control evaluation of every DNA array analysis. By controlling for sporadic sample or array failures, "mining" of expression data can be performed with an even greater level of confidence.
Antibody-Generating Systems
We use bacteriophage antibody display libraries proprietary to MorphoSys to generate and isolate reagent antibodies. We are using Medarex's proprietary HuMAb mice for making fully-human therapeutic antibodies. As a result of our collaborative relationship with Medarex, we have special access to these mice. We immunize them with the proteins that we make as a result of translating our therapeutic targets. As with our other technology-dependent activities, we deploy multiple means to achieve our important ends.
Human Tissue Arrays
Tissue array technology provides a new method for a highly parallel molecular profiling of tissue specimens. This technology allows for a rapid, large-scale molecular analysis of hundreds of disease-derived or normal tissues. We have acquired and continue to develop tissue array technology to further characterize the genes chosen by our DNA array based analysis. The arrays are constructed by acquiring small (0.6mm-2mm) cylindrical core biopsies from tens to hundreds of individual tissue samples. These tissue cores are then arranged into a single array block the size of a microscope slide. Hundreds of identical slides can be sliced from such a tissue array block and probed for mRNA or protein expression. A single hybridization reaction of a tissue array with a probe for a specific gene activity provides information on hundreds of specimens in parallel. This molecular approach allows us to determine specific gene activity at the level of the individual cells. In addition, the large numbers of patient specimens surveyed provide statistically significant conclusions regarding the target incidence within the disease population. Taken together, DNA arrays and tissue arrays allow for large scale rapid discovery and validation of pathogenic cell type specific gene activity.
Experimental Model Systems
Eos makes extensive use of pre-clinical experimental models systems to further assess the specificity and efficacy of antibodies made to our targets. We do in vivo imaging experiments in multiple proprietary systems, including:
Angiogenesis primary cell culture assay
* Human endothelial cells are cultured in a three-dimensional matrix system that allows genome-based interrogation of the formation of tubular vessels with lumens and tight junctions.
* Angiogenesis has pathogenic relevance across many diseases, including Eos' internal drug target discovery programs in oncology and inflammation.
* A database has been generated with over 3 million independent gene measurements from multiple experiments with numerous time points each.
In vivo models
* More than 20 human cancer cell lines that we profile both as cultured cells and excised xenograft tumors.
* Intrinsic mouse disease models systems, such as collagen induced arthritis and APC mutant mice.
CORPORATE COLLABORATORS
In April 1998, we entered into a Chip Supply Agreement with Affymetrix whereby Eos has Gold EasyAccess to the GeneChip® technology. In February 1999, we acquired from Affymetrix an internal research use license to all Affymetrix existing intellectual properties for the generation of and analysis using synthetic DNA arrays. Affymetrix manufactures and sells exclusively to Eos custom GeneChips® designed by Eos using our proprietary mask design and genome-prediction technology.
www.Affymetrix.com
In March 2000, Eos and Medarex entered into a multi-year collaboration providing Eos with broad access to Medarex' HuMAb-Mouse technology, including a breeding stock of HuMab mice, and options to take up to 15 commercial licenses for antibodies developed to Eos targets. Seperately, in April 2001 Eos and Medarex entered into an applied genomics collaboration, the result of restructuring a prior co-development agreement. Eos and Medarex will jointly develop and commercialize fully human monoclonal therapeutic products generated using the Medarex technology, to multiple disease targets identified by Eos. Eos and Medarex will share costs and responsibilities leading to the anticipated commercialization of therapeutic products, including preclinical and clinical development and marketing efforts.
www.Medarex.com
In December, 2000 Eos entered into a collaborative licensing agreement. They will generate and deliver to us phage derived antibodies that originate from animals, including from Medarex's HuMab mice, that we, or they, have immunized with our specific target molecules. We are obligated to pay a fee for each set of phage antibodies delivered, and annual maintenance fee subsequent to the delivery date, and milestones and royalties for products resulting from their phage system technology.
www.biosite.com
In June, 2001, we entered into a collaboration to use Seattle Genetics' toxic payload technology with our proprietary monoclonal antibodies directed against our novel cancer targets, derived from their analyses of the human genome. Seattle Genetics has fully synthetic, highly potent, novel drugs that can be used as payloads to dramatically increase the potency of monoclonal antibodies as therapeutic agents. Under the multi-year agreement, Seattle Genetics will provide broad access to their proprietary, novel classes of cell-killing drugs and their proprietary, specialized linkers, used to attach the drugs to antibodies. Eos will apply this technology towards developing therapeutic antibodies linked to these toxic payloads, to specifically target and kill tumor cells. Under the terms of the agreement, Seattle Genetics will provide access both to its current technology of novel, fully synthetic payloads as well as any new technology developed during the course of the collaboration. Eos pays an upfront technology access fee, milestone payments and royalties on net sales of any resulting products. Eos will be responsible for product development, manufacturing and marketing of any products generated through the collaboration.
www.seattlegenetics.com
In September 2000, we established a collaboration with Biogen, Inc. for the discovery and validation of targets for therapeutic antibodies and proteins we generate from our analyses of breast cancer. We have agreed to provide Biogen with antibody targets that have been specificity- and efficacy-validated on human tissue and in preclinical model systems, which Biogen may or may not accept to develop therapeutic antibodies and proteins for commercialization. In connection with this collaboration, Biogen made an up-front cash payment to us and committed to support our research activities under the collaboration for a period of four years. For each target that Biogen accepts, we are entitled to receive a milestone payment. As Biogen's accepted targets progress through additional preclinical, and then clinical, development to market approval, Biogen is obligated to pay us additional milestone payments, and if any product is ultimately developed and marketed, royalty payments. In addition, we may agree to generate and co-develop with Biogen fully human antibodies against selected breast cancer targets under terms to be negotiated. The four-year research program associated with this collaboration is overseen by a joint research management committee. Biogen participated in our last private round of financing.
www.Biogen.com
In July of 2000, we acquired from MorphoSys a license to HuCal phage antibody display libraries for use in generating and isolating reagent antibodies.
www.morphosys.com
In June 2000, we established a collaboration with Aventis-Pasteur, Inc. to develop cancer vaccines in two therapeutic areas. We have agreed to provide Aventis-Pasteur with specificity-validated targets which Aventis-Pasteur may or may not accept for commercialization of vaccine therapies. In connection with this collaboration, Aventis-Pasteur made a cash payment to us and also committed to provide financial support for our target discovery activities for a two-year period. For each target that Aventis-Pasteur accepts, we are entitled to receive a milestone payment. As Aventis-Pasteur progresses accepted targets through preclinical and clinical development to market approval, Aventis-Pasteur is obligated to pay us additional milestone payments, and if any product is ultimately developed and marketed, royalty payments. Aventis Pasteur is a world leader in vaccines and produces more than one billion doses of vaccines every year to immunize 400 million people around the world. Aventis Pasteur, headquartered in Lyons, France, is one of the pharmaceutical activities of Aventis SA, a world leading company in life sciences.
www.aventispasteur.com
ACADEMIC COLLABORATORS
Eos has established a number of enabling academic relationships to provide it with access to high quality human tissues, medical outcome data, and animal models of human diseases. The institutions and lead investigators are:
* Murdoch Childrens Research Institute, Melbourne, Australia
Lead Investigator: Deon Venter, M.D., Ph.D.
* Princeton University/Rockefeller University, New York, NY
Lead Investigator: Arnold Levine, Ph.D.
* Case Western Reserve, Cleveland, OH
Lead Investigator: Sandy Markowitz, M.D., Ph.D.
* The Garvan Institute of Medical Research, Sydney, Australia
Lead investigator: Robert Sutherland, Ph.D.
* University of Duesseldorf, Dussedorf, Germany
Lead investigator: Matthias Schneider, M.D.
* University of Halle, Halle, Germany
Lead investigators: Stefan Burdach M.D., Ph.D. and Rolf Silber, M.D.
* University of California, San Francisco, CA
Lead investigator: Verna Gibbs, M.D.
* Cedars-Sinai Medical Center, Los Angeles, CA
Lead Investigator: David Agus, M.D.
* University of Aarhus, Arhus, Denmark
Lead Investigator: Torben Orntoft, Ph.D. |
