At Triangulum, our mission is to provide scientists in the Biopharma industry with world class pre-clinical pharmacology services.
Triangulum is founded with the vision of supporting scientists and innovators accelerate drug development, leveraging our portfolio of extensive industry experience in small molecule, biologics and RNA-based therapeutics. Our customer-centric approach and commitment enables you to bring modern medicines rapidly to the patients.
The company is headquartered, and has its operations in San Diego, California. Triangulum consists of a team of professionals with a collective experience of over 60 years. Together, we have authored over 100 publications, abstracts, scientific presentations, book chapters and patents. Several of the compounds our scientists have previously worked on are now in clinical phases of development.
Nonalcoholic Steatohepatitis (NASH) is a progressive form of Nonalcoholic Fatty Liver Disease (NAFLD) and has emerged to be a critical public health issue. It is anticipated that NASH will become the most common indication for liver transplantation in next ten years in the United States. NASH has strong association with diabetes, obesity and metabolic syndrome, and this disease is characterized by excessive triglyceride storage in the liver, insulin resistance and progress through stages of inflammation, fibrosis to cirrhosis and associated with the risk of hepatocellular cancer. There is currently no FDA-approved therapy for NASH and thus it becomes one of the major unmet medical needs of the present time.
Triangulum offers CRO services with extensive expertise in the following mouse models of NASH to our clients:
Normal mice fed with diet enriched in fat (40% kcal), fructose (22% by wt), and cholesterol (2% by wt). This model develops clinically relevant features of NASH over a prolonged period of time.
ob/ob mice fed with high fat diet Model
These mice are severely obese due to leptin deficiency and predisposed to develop steatohepatitis. ob/ob mice fed with diet enriched in fat (40% kcal), fructose (22% by wt), and cholesterol (2% by wt) develop clinically relevant features of NASH in a shorter duration.
Normal mice fed with MCD diet Model
MCD diet fed model shows the features of NASH-related inflammation and fibrosis that have been implicated in human NASH progression.
db/db mice fed with MCD diet Model
These mice are obese with insulin resistance, severe type 2 diabetes, and fatty livers due to a functional defect in their leptin receptor. MCD diet in this model exhibit the features of NASH-related inflammation and fibrosis that have been implicated in human NASH progression
Normal mice are fed with diet enriched in fat and diabetes is induced by streptozotocin administration. This model develops clinically relevant features of NASH where diabetes exacerbates the NASH phenotype.
Muscle diseases can be caused by metabolic disorders or other genetic mutations. Muscular dystrophy is the most common form and characterized by progressive weakness and degeneration of the skeletal muscles.
Triangulum brings years of experience in preclinical pharmacology studies of drug candidates in muscle disease areas such as Myotonic Dystrophy Type 1 (DM1). We offer services specific to your needs by conducting efficacy studies with your investigative compounds in various muscle diseases. At present we offer our expertise in the following mouse models.
HSALR mouse model of Myotonic Dystrophy Type1 (DM1)
In humans DM1 is caused by an expanded CTG (or CUG at RNA level) repeat in the 3′ UTR of DMPK (Dystrophia myotonica Protein kinase) gene. The HSALR (Human Skeletal Actin Long Repeat) transgenic mouse is the widely used model in DM1 research. These mice express high levels of CUGexp RNA in skeletal muscle and have expanded CTG repeat in the 3′ UTR of a human skeletal actin (hACTA1) gene. The CUGexp transcripts are retained in nuclear foci, along with splicing factors in the Muscleblind-like (MBNL) family, and the sequestration of Muscleblind leads to misregulated alternative splicing and these pathological changes affect the muscle function known as Myotonia.
mdx model for Duchenne Muscular Dystrophy (DMD)
DMD is caused by mutations in the dystrophin gene resulting in the absence of dystrophin protein. The mdx mouse model for DMD is routinely used to study the efficacy and toxicity of disease modifier compounds. The mdx mouse model does not have a functional dystrophin protein in its muscle since a nonsense point mutation in exon 23 of the dystrophin gene results in the premature termination of translation in dystrophin expression. Nonetheless, the mdx mouse model is extremely valuable in assessing the activity of drugs as well as performing proof-of-concept experiments.
Evaluation of drug activity in the muscles of wild type mice
Our team also offers preclinical screening services with your drug candidate in normal wild type mice that target muscle. We work with our clients in providing scientific guidance, customized study design, end-point analysis, histopathology services, and will assist you with the interpretation of the data.
Triangulum offers CRO services with extensive expertise in conducting preclinical efficacy, proof-of-concept and mechanism of action studies in various animal models of type 2 diabetes. Our scientists have outstanding track record of working with ob/ob, db/db, DIO-Streptozotocin, DIO mice as well as Zucker Diabetic Fatty (ZDF) rats and DIO-Streptozotocin rats. Our team has the skills and experience needed to evaluate your preclinical drug candidates such as small molecules, biologics and RNA therapeutics in acute and chronic efficacy studies. We provide hyperinsulinemic-euglycemic clamp studies, OGTT, IPGTT, ITT and histopathology services. Our scientists provide professional interpretation of the preclinical efficacy data to accelerate your drug development.
Drug Metabolism and Pharmaco-Kinetic (DMPK) studies are integral to understand the life and/or stability of the drug inside the organism and thus aid in determination of the required optimal dosage of the drug. While various factors such as Absorption, Distribution, Metabolism and Excretion could have mono- or multi-variate influence on the bioavailability of the drug once administered, a proper understanding of these processes is often necessary for drug development in pre-clinical stages and could provide valuable information for dose selection in First in Human (FIH) clinical trials. Further, knowledge gained from these studies is critical for repeated compound administration.
Our research team has extensive experience in rodent disease models, a variety of routes for investigative drug administration (IP, IV, IM, SC, PO) and extraction of various tissues to determine the bioavailability of the drug in target organs.
Our DMPK analysis team has significant experience in the analytical methods of drug development including but not limited to:
Our team can also assist with data analysis utilizing either non-compartmental or compartmental (single and/or multi-compartmental) modelling approaches and statistical analysis using SAS software.
In addition, we perform PD studies on the following NASH/NAFLD Models, Metabolic Disease Models and Muscle Disease Models.
Genetic Disorder Animal Models Services
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