1. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Altogen Labs 4020 S Industrial Dr Suite 130 Austin TX 78744 USA info@altogenlabs.com 512.433.6177 Benefits of Xenograft Develop new therapeutic agents quickly, efficiently and cost effectively Evaluate the efficacy and toxicity of potential therapeutic agents Evaluate target compound activity using in vivo system (human cells) Predict cytotoxicity of cancer drugs Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another. www.signalsblog.ca www.wikipedia.org

2. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics In vivo xenograft efficacy evaluations remain the gold standard and the workhorse of oncology preclinical research. Xenograft models combine the advantages of working with human cancers with the physiological relevance of an in vivo host. Typically, immunodeficient mice serve as hosts for a wide variety of human tumors, effectively serving as proxies for human subjects. Xenograft models remain a mainstay in oncology research, playing a key role in drug discovery and development. The Gold Standard in Oncology

3. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Pipeline Xenograft Assay I We design your experiment based on your project requirements. Through years of experience and literature search we guarantee optimal experimental setup according to selection of mice stain, cell lines, inoculation and dosage. Pipeline Assay II - test a compound You send us a compound and cell line to establish xenograft. We establish xenograft animal models and test compound activity and how it affects tumor growth in an established xenograft model. Pipeline Xenograft Assay III - test a cell line You send us a cell line and we test it’s ability to establish tumor growth in standard immunodeficient mice. Assay Pipelines

4. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics How does the test compound affect tumor growth? Does the test compound inhibit tumor invasion or metastasis? Localization of test compound in the tumor? Define drug characteristics: Bioavailability Toxicity Efficacy Potency Is cell line tumorigenic? Changes in gene expression upon treatment or gene manipulation ParamHow does gene manipulation in a cell line affect following parameters: Tumor growth, Invasiveness, Metastasis Experimental Objectives of Compound Testing www.skyepharma.com

5. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Basic Study Design Xenograft studies can be designed to identify lead compounds, optimize dose schedules, and identify combination strategies.

6. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Use in-house or customer-provided cell lines or tumor Begin testing a compound immediately after injecting mice with tumor cells (unstaged) or once the tumors reach a certain size (staged) Assign mice to groups randomly or stratify them by body weight, tumor size, disease factors, or any combination of parameters Administer test compounds by any of the following methods: topically, IP, IV, SC, PO, high pressure tail vein, osmotic minipumps (SC or IP), SC drug pellets, or in the food or water Snap freeze harvested tumors or fix them for histology or other specialized assays Analyze blood chemistry at various times throughout the study Service Options

7. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Cell Line Organ Disease A549 Lung Carcinoma DU145 Prostate Carcinoma PC3 Prostate Adenocarcinoma LNCaPProstateCarcinoma MDA-MB-231 Breast Adenocarcinoma FaDuPharynx Squamous carcinoma Caki -1Kidney Clear Cell Carcinoma Caki - 2 Kidney Clear Cell Carcinoma PANC-1 Pancreas Epithiloid Carcinoma SK-MEL-2 Skin Malignant Melanoma SK-OV-3 Ovary Adenocarcinoma U-87 MG BrainGlioblastoma/ Astrocytoma A431 Epidermis Epidermoid Carcinoma SW-480Colon Adenocarcinoma HeLa CervixAdenocarcinoma Sample of Cell Lines Maintained at Altogen Labs

8. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Growth rates for different cell lines

9. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Route of dose: Intratumoral Intramuscular Oral Intravenous Intratracheal Subcutaneous Intraperitoneal Frequency of dose Duration of dose Administration Options www.patient-derived-xenograft-services.com

10. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Estimated tumor volume (L x W 2 /2) Mean/median time to specified tumor volume Survival time to specified tumor volume Tumor doubling time Tumor growth inhibition (TGI) Tumor growth delay (TGD) Increased life span (ILS) Tumor cell kill rate Endpoints

11. Provider of Global Contract Research Services Accelerating Preclinical Research, Drug Discovery & Therapeutics Clinical observations every day Haematology analysis (blood cell count) Clinical chemistry profile (of urine and plasma) Evaluate the degree of metastasis. Characterization of the tumor (necrosis, etc) The tumor is divided and preserved for further analysis Cryo-preservation (for cell culture) Formalin fixed tumors and tissues (for histopathological and immunostaining analysis) RNAlater fixed tumors and tissues (for RNA and DNA isolation, and gene expression analysis) Additional Analysis Options