ASET Platform

Preclinical studies are required to ensure that any therapeutic candidate meets rigorous standards before being tested in any human subjects. This phase takes a large portion of the total time to develop the drug candidates and represent a critical time to identify failures before significant investment has been sunk. It is of vital importance that companies identify the compounds that have the highest potential for success and separate them for the large number of discovered chemical entities with as little investment as possible. Every dollar spent on a compound of low therapeutic yield or with a poor safety profile is a dollar lost as these compounds will never make it to any type of Pharmaceutical market. It is estimated that for every compound approved by regulatory bodies, 5,000 – 10,000 compounds are discovered and the remaining compounds abandoned. It is a strategic and financial necessity for a company to identify the winners faster and at a lower cost than current testing protocols allow.

Innovascreen's Avian System for Evaluating Therapeutics (ASET) Platform is a comprehensive suite of in vivo assays for faster preclinical validation of compounds at a lesser cost than conventional animal models while providing stronger, more compelling results. A key component of the ASET platform is Innovascreen’s novel high throughput intravital imaging system. This platform allows us to acquire richly detailed 3D time-lapse imagery of up to six distinct molecular features in real time. The impact of a drug candidate on human tumors and tumor cells at the primary tumor or metastatic sites can be assessed.

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Intravital Imaging Technology

As a core component of the ASET Platform, Innovascreen’s novel intravital imaging system utilizes validated human tumor models in the proprietary preclinical analytical platform. The technology can evaluate the migratory and invasive behavior of human tumor cells at the site of the primary tumor as well as metastatic sites. The model permits long-term imaging and the quantitative assessment of cell motility parameters (including velocity, persistence and turn-angle). Furthermore, the intravital imaging platform is integrated with our quantitative metastasis and angiogenesis assays allowing quantification of individual metastatic steps.

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In Vivo Assays

Angiogenesis

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential in normal developmental and regenerative processes. Aberrant angiogenesis is a cornerstone of numerous diseases, including cancer, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, psoriasis, and more than 70 other conditions.

We offer a high throughput, scalable in vivo angiogenesis assay that allows a quantitative evaluation of one to thousands of compounds simultaneously in as little as two weeks. The scalable nature of the assay allows us to test a dozen or thousands of subjects simultaneously. Because our Angiogenesis Assay is comparable in cost and duration to in vitro methods, it can be scaled up to provide enough data points to achieve a high degree of statistical significance. In contrast, mouse models can be lengthy, are expensive, and the results variable.

The platform is customizable, allowing Innovascreen to evaluate pro- or anti-angiogenic activity as is required and can be utilized to interrogate distinct mechanisms of action (ie. VEGF-mediated, MMP-mediated).

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Tumor Growth and Metastasis

The most deadly aspect of cancer is its ability to spread, or metastasize – it is an important clinical endpoint that is becoming an important drug target. Innovascreen offers a panel of in vivo metastasis assays that can precisely measure the activity of drug entities on tumor growth, invasion, migration, intravasation, extravasation and metastasis to distant organs. Our powerful assay can accurately detect less than 10 metastatic tumor cells per organ, allowing us to differentiate (with statistical significance) between drug candidates in as little as two weeks.

A key component of the ASET platform is Innovascreen’s novel high throughput intravital imaging system. This platform allows us to acquire richly detailed 3D time-lapse imagery of up to six distinct molecular features in real time. The impact of a drug candidate on the migratory and invasive behavior of tumor cells at the primary tumor or metastatic sites can be assessed. Innovascreen’s metastasis assays can measure the ability of drug candidates to inhibit dissemination of tumor cells from the primary tumor to secondary sites, or to impact each step of the metastatic cascade individually.

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Tumor cell invasion and migration

The most lethal aspect of cancer is its ability to move away from the primary site and colonize distant sites in the body. To achieve this, cancer cells must acquire the ability to migrate through the tissues surrounding the tumor. Using our 3D time-lapse imaging platform, we visualize and quantitatively document the capacity of a drug candidate to impact the migration of human tumors in vivo. Detailed information about the effect of drug administration on tumor cell migration within the primary and/or metastatic tumor microenvironment is obtained.

Intravital imaging and quantitation of tumor cell migration. We can visualize and quantify human tumor behavior in real time. These images demonstrate our ability to track individual cells as they invade the surrounding stroma. (Zijlstra et al. Cancer Cell 2008)
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Vascular Permeability

Uptake of cancer therapeutics into a tumor can be enhanced with agents that make the vasculature inside the tumor more permeable or "leaky". Measuring vascular permeability using traditional assays is highly variable, costly and time consuming. Using our 3D time-lapse imaging platform, we can visualize and quantitatively document the capacity of a drug candidate to increase the permeability of vasculature both inside and outside of the tumor in vivo. Detailed information is obtained regarding the timing and specific regions of increased permeability.

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Tumor targeting and biodistribution

Variations of small molecule investigational drugs based on a similar platform may exhibit dramatically different abilities to accumulate in target tissues in vivo. This, in turn, can have a significant effect on both the activity of a drug candidate and the potential side-effects. Using our 3D time-lapse imaging platform, we will visualize and quantitatively document the capacity of a drug candidate to target human tumors in vivo. Detailed information about the timing and specific localization of drug both at the tumor site and in distant metastases is obtained.

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