SBIR-STTR Award

The overall goal of this program is to develop an oral replacement for injecting insulin. The central premise of this work is that a small molecule called BG-148, or similar molecules, can be taken orally in place of injecting insulin to aid in glycemic control. BG-148 could completely replace insulin injections or could reduce insulin injections by half. To begin clinical testing to evaluate this premise, a formal, regulated toxicological program must be conducted, and BG-148 must be manufactured for human use. The specific aims of this proposal are designed to address these obstacles. PHASE I SPECIFIC AIM: Make larger quantities (? 2 kg) of BG-148. This aim will produce sufficient amounts of BG-148 to complete all preclinical studies required to begin human testing. Aim 1 will also generate analytical knowledge, such as analytical methods to characterize the drug?s stability, identity, strength, and purity, which will enable the manufacturing of BG-148 for human use and the completion of all preclinical studies required to proceeded to humans. PHASE II SPECIFIC AIMS: AIM 2: Complete a 28-day repeat-dose study in animals with type I diabetes. Aim 2 will help define (a) the therapeutic oral dose levels of the BG-148, (b) the degree to which BG-148 is able to lower blood glucose, and (c) BG-148?s potential to induce hypoglycemia, diabetic ketoacidosis, or other adverse events. This information will allow us to power and design initial human trials. AIM 3: Define the no-observed-adverse-effect Level (NOAEL) and derive the Maximum Recommended Starting Dose (MRSD) for first-in-human clinical trials. There is currently insufficient data to determine the dose levels at which toxicity might occur in upon repeat dosing with BG-148. Not knowing these dose levels prevents us from initiating human trials. This aim will generate the required safety data to enable clinical trials. This program will lead to the identification of a new class of orally bioavailable molecule that is capable of lowering blood glucose with an activity approaching that of insulin. Such discovery would lead to a novel therapeutic for glycemic control. Clinical work represents the only method to determine the extent to which BG-148, or similar molecules, would make useful and safe oral therapeutic that are capable of reducing the need to inject insulin. This project is designed to reach this clinical stage as early as possible.

Project Terms:
Acute; Address; Adverse event; American; analytical method; Animals; Automobile Driving; base; Beta Cell; Bioavailable; Blood Glucose; Clinical; Clinical Trials; cost; Data; design; Development; diabetes control; diabetes management; Diabetes Mellitus; Diabetic Ketoacidosis; dosage; Dose; Drug Stability; Evaluation; Family suidae; first-in-human; Formulation; Glucose; glycemic control; Goals; Health; Health Care Costs; Human; Human Activities; Hypoglycemia; Hypoglycemic Agents; Individual; Injections; Insulin; Insulin-Dependent Diabetes Mellitus; Intellectual Property; Investigational Drugs; Knowledge; Lead; Legal patent; Medical Care Costs; Methods; Miniature Swine; Molecular; Monitor; Mus; No-Observed-Adverse-Effect Level; Non-Insulin-Dependent Diabetes Mellitus; novel therapeutics; Oral; Organ; Patients; Pharmaceutical Preparations; Phase; pill; preclinical study; prevent; Productivity; programs; Public Health; research clinical testing; Safety; small molecule; societal costs; Tablets; Testing; Therapeutic; Therapeutic Index; Toxic effect; Toxicology; type I and type II diabetes; United States; Work;

The overall goal of this program is to develop an oral replacement for injecting insulin. The central premise of this work is that a small molecule called BG-148, or similar molecules, can be taken orally in place of injecting insulin to aid in glycemic control. BG-148 could completely replace insulin injections or could reduce insulin injections by half. To begin clinical testing to evaluate this premise, a formal, regulated toxicological program must be conducted, and BG-148 must be manufactured for human use. The specific aims of this proposal are designed to address these obstacles. PHASE I SPECIFIC AIM: Make larger quantities (? 2 kg) of BG-148. This aim will produce sufficient amounts of BG-148 to complete all preclinical studies required to begin human testing. Aim 1 will also generate analytical knowledge, such as analytical methods to characterize the drug’s stability, identity, strength, and purity, which will enable the manufacturing of BG-148 for human use and the completion of all preclinical studies required to proceeded to humans. PHASE II SPECIFIC AIMS: AIM 2: Complete a 28-day repeat-dose study in animals with type I diabetes. Aim 2 will help define (a) the therapeutic oral dose levels of the BG-148, (b) the degree to which BG-148 is able to lower blood glucose, and (c) BG-148’s potential to induce hypoglycemia, diabetic ketoacidosis, or other adverse events. This information will allow us to power and design initial human trials. AIM 3: Define the no-observed-adverse-effect Level (NOAEL) and derive the Maximum Recommended Starting Dose (MRSD) for first-in-human clinical trials. There is currently insufficient data to determine the dose levels at which toxicity might occur in upon repeat dosing with BG-148. Not knowing these dose levels prevents us from initiating human trials. This aim will generate the required safety data to enable clinical trials. This program will lead to the identification of a new class of orally bioavailable molecule that is capable of lowering blood glucose with an activity approaching that of insulin. Such discovery would lead to a novel therapeutic for glycemic control. Clinical work represents the only method to determine the extent to which BG-148, or similar molecules, would make useful and safe oral therapeutic that are capable of reducing the need to inject insulin. This project is designed to reach this clinical stage as early as possible.

Public Health Relevance Statement:
Despite advancements in the management of diabetes, such as oral hypoglycemic agents and insulin therapies, it is estimated that only half of 29 million Americans with diabetes are able to achieve ideal levels of blood glucose. As a result, in 2012, diabetes was estimated to cost the United States $245 billion: $176 billion in direct medical costs and $69 billion in reduced productivity. The proposed work is relevant to public health because it will enable the development of a therapeutic to control diabetes, reducing individual burden, along with the acssciated healthcare and societal cost.

NIH Spending Category:
Autoimmune Disease; Diabetes; Prevention

Project Terms:
Acute; Address; Adverse event; American; analytical method; Animals; Automobile Driving; base; Beta Cell; Bioavailable; Blood Glucose; Clinical; Clinical Trials; cost; Data; design; Development; diabetes control; diabetes management; Diabetes Mellitus; Diabetic Ketoacidosis; dosage; Dose; Drug Stability; Evaluation; Family suidae; first-in-human; Formulation; Glucose; glycemic control; Goals; Health; Health Care Costs; Human; Human Activities; Hypoglycemia; Hypoglycemic Agents; Individual; Injections; Insulin; Insulin-Dependent Diabetes Mellitus; Intellectual Property; Investigational Drugs; Knowledge; Lead; Legal patent; Medical Care Costs; Methods; Miniature Swine; Molecular; Monitor; Mus; No-Observed-Adverse-Effect Level; Non-Insulin-Dependent Diabetes Mellitus; novel therapeutics; off-patent; Oral; Organ; Patients; Pharmaceutical Preparations; Phase; pill; preclinical study; prevent; Productivity; programs; Public Health; research clinical testing; Safety; small molecule; societal costs; Tablets; Testing; Therapeutic; Therapeutic Index; Toxic effect; Toxicology; type I and type II diabetes; United States; Work