SBIR-STTR Award

Type 2 diabetes (T2D) is chronic disease characterized by high blood glucose and rapidly emerged as a global health care problem that threatens to reach pandemic levels by 2030. Nearly 350 million people worldwide are currently affected by diabetes. Diabetes is a major cause of heart disease and stroke and also leads to other complications, such as vision loss, kidney failure, and amputations of legs or feet. The effective drugs for treatment of T2D, such as insulin and glucagon-like peptide 1 (GLP- 1), require injections, which are inconvenient and expensive. Development of safer, more effective, and more convenient oral medicines, therefore, will be necessary for preventing the diabetes pandemic. The product of this SBIR is the oral dosage form of DT-109 for the treatment of T2D. DT-109 is a tripeptide that effectively lowered blood glucose in several T2D mouse models by increase the GLP-1 and insulin levels when orally administered. Since DT-109 is comprised of natural occurring L-amino acids, it is considered to be a safer, cheaper, and a convenient pharmaceutical intervention for T2D patients. The long-term goal of this SBIR is to complete preclinical development and identify a partner or investor consortium to fund clinical trials for DT-109 as an oral therapeutic for T2D. Diapin Therapeutics has demonstrated that DT-109 acts through a G-protein coupled receptor (GPCR) to elicit its activity and high throughput screening of GPCR libraries showed the 3 hits as an agonist among 160 GPCRs. This phase I hypothesis is that at least one of 3 GPCRs are essential for DT-109 to elicit its activity. There are two specific aims in this phase I SBIR proposal. Aim 1 is to confirm the results from high throughput screening and identify the specific GPCR(s) required for the effect using a gain-of-function model. Aim 2 is to determine the functional importance of the GPCR(s) using a loss-of-function model. Characterization of the MOA of DT-109 is critical for our understanding of the pharmacology of DT-109. The phase II of this SBIR will carry on the studies on pharmacokinetics/toxicokinetics and complete the data set for opening IND for DT-109. The patent for the oral dosage form of DT-109 has been issued and the identification of DT-109 targets will help us to bridge with big Pharmas to open clinical trials for DT-109 as an oral therapeutic for T2D.

Public Health Relevance Statement:


Public Health Relevance:
In this Phase I SBIR, Diapin Therapeutics plans to characterize the mechanism of action of DT-109 for the development of DT-109 as an oral therapeutic for type 2 diabetes, a metabolic disease that currently affects nearly 350 million people worldwide. Because the most effective drugs on the market require injections, development of this new oral therapy is necessary for preventing diabetes pandemic. The goal of this SBIR project is to complete the pre-clinical development and open clinical trials leading t commercialization of DT-109 as a novel therapeutic for type 2 diabetes.

Project Terms:
Affect; Agonist; Amino Acids; Amputation; Animals; Blindness; Blood; Blood Glucose; Cell Line; Cells; Cessation of life; Chronic; Chronic Disease; Clinical Trials; commercial application; commercialization; Complications of Diabetes Mellitus; cost; Data Set; Development; Diabetes Mellitus; Diabetic mouse; Diagnosis; Disease; Dosage Forms; Drug Kinetics; Drug or chemical Tissue Distribution; economic cost; effective therapy; foot; Funding; G-Protein-Coupled Receptors; gain of function; global health; glucagon-like peptide; Glucose; Goals; Health; Healthcare; Heart Diseases; high throughput screening; Injectable; Injection of therapeutic agent; Insulin; Intervention; Kidney Failure; Knockout Mice; Lead; Leg; Legal patent; Libraries; Licensing; loss of function; Marketing; Medical; Metabolic Diseases; Michigan; Modeling; Non-Insulin-Dependent Diabetes Mellitus; novel; novel therapeutics; Oral; Oral Administration; Oral Medicine; overexpression; pandemic disease; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Play; pre-clinical; prevent; public health relevance; Receptor Mediated Signal Transduction; Role; Safety; Small Business Innovation Research Grant; Small Interfering RNA; Staging; stem; stroke; Technology; Testing; Therapeutic; Toxicokinetics; Toxicology; Universities

Type 2 diabetes is a chronic debilitating disease that threatens to reach pandemic level by 2030. Nearly 350 million people worldwide are currently affected by diabetes and more than 70% of patients with type 2 diabetes die of cardiovascular causes. However, no particular diabetes medication to date is considered superior in the minimization of the risk of cardiovascular diseases associated with type 2 diabetes. Therefore, development of new anti-diabetic drugs that also decreases the risk of cardiovascular diseases will be highly desirable and needed. The product being developed is DT-110, a tripeptide, as an oral therapeutic for treatment of type 2 diabetes. Technological innovation is the application of tripeptide as an oral dosage form to treat human diseases. In our phase I study, we found that DT-110 activates G protein coupled receptor D (MrgprD) signaling pathway that has not been reported to be linked to metabolic diseases. Since activation of MrgprD has been shown to play a protective role in cardiovascular system, our results suggest that DT-110 may have beneficial effects on cardiovascular system in addition to controlling blood glucose levels, and therefore, potentially be a first anti-diabetic drug that can minimize the risk of cardiovascular diseases associated with type 2 diabetes. The long-term goal of this SBIR is to complete the preclinical study on DT-110, file IND, and commercialize it as a new class of anti-type 2 diabetes drugs capable of reducing the risk of cardiovascular diseases associated with type 2 diabetes. The mechanism of action of DT-110 is different from that of the currently available medications for type 2 diabetes. In the Phase II study, we will test the hypothesis that DT-110 specifically acts on this novel signaling pathway to effectively lower the blood glucose levels and protecting cardiovascular system in the patients with type 2 diabetes. Specific aims of this Phase II SBIR are 1) to examine the therapeutic roles of DT-110 in controlling glucose levels and in regulation of blood vessel vasodilation in the genetically modified mice, 2) to develop an enteric coated DT-110, and 3) to determine the blood glucose lowering effect of DT-110 in a large animal model. This study will provide significant information for our understanding of novel mechanism of action of DT-110 and its efficacy in various animal models to support IND filing, and ultimately lead to successful development of a new drug for treatment of type 2 diabetes, which may also has a protective effect on cardiovascular system.

Public Health Relevance Statement:


Public Health Relevance:
In this Phase II SBIR, Diapin Therapeutics plans to develop DT-110 as an oral anti-type 2 diabetes drug that potentially decreases the risk of cardiovascular diseases associated with type 2 diabetes, a metabolic disease that currently affects about 29.1 million people In USA. No particular diabetes medication to date is considered superior in the minimization of the risk of cardiovascular diseases and any new drugs for treatment of type 2 diabetes that concurrently decrease the risk of cardiovascular diseases will be much needed. The goal of this SBIR project is to complete the pre-clinical development and open clinical trials leading to commercialization of DT-110 as a novel therapeutic for treatment of type 2 diabetes.

NIH Spending Category:
Cardiovascular; Diabetes; Heart Disease; Prevention

Project Terms:
Adoption; Affect; Animal Model; Animals; Antidiabetic Drugs; Attenuated; Blood Glucose; blood glucose regulation; Blood Vessels; cardiovascular disorder risk; cardiovascular risk factor; Cardiovascular system; Chronic; Clinic; Clinical Trials; commercial application; commercialization; Critical Pathways; Data; Development; Diabetes Mellitus; diabetes mellitus therapy; Disease; dosage; Dosage Forms; Dose; Drug Formulations; drug market; Endocrinologist; Enteral; Eye; forest; G-Protein-Coupled Receptors; Germany; glucagon-like peptide; glycemic control; Glycosylated hemoglobin A; Goals; Heart; high throughput screening; human disease; in vivo; insulin secretagogues; Investigational Drugs; Kidney; Lead; Libraries; Licensing; Link; Marketing; Metabolic Diseases; Michigan; Modeling; Mus; Nerve; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; nonhuman primate; novel; novel therapeutics; Oral; Oral Administration; Organ; pandemic disease; Patients; Pharmaceutical Preparations; Phase; phase 1 study; phase 2 study; Play; pre-clinical; preclinical study; prevent; Production; protective effect; public health relevance; Rattus; Regulation; Reporting; Resources; risk minimization; Role; Signal Pathway; Signal Transduction; Small Business Innovation Research Grant; Staging; success; technological innovation; Testing; Therapeutic; Universities; Vasodilation