R44DK125126

Targeting Galectin-3 to overcome insulin resistance in type 2 diabetes - Project Summary/Abstract

Obesity-mediated insulin resistance is a hallmark of type 2 diabetes (T2D), which accounts for ~90% of all diabetes. Despite many drugs that are available to treat T2D, there is no FDA-approved drug that directly works on the insulin receptor (IR) to overcome insulin resistance.

Recent studies show that Galectin-3 (GAL3) can bind directly to the IR and inhibit downstream IR signaling causing insulin resistance and impaired glucose tolerance in obesity-induced T2D. Our scientific premise is that we have developed a very potent GAL3 antagonist, TFD100, from a natural dietary source.

The primary objective of this Phase II proposal is to complete the preclinical studies required for our IND submission to the FDA to enable the initiation of a first-in-human Phase 1 clinical trial. Successful completion of our proposed aims will achieve a significant value inflection point for the company, positioning us well for either partnering or a capital raise.

The proposed research embodies technological innovation in two areas: 1) this will be the first FDA-approved biologic therapeutics based on a natural carbohydrate compound; 2) TFD100's picomolar affinity to GAL3 has many advantages including overcoming the common saturation issue related to antigenicity.

An anticipated corollary benefit of the proposed studies includes the elucidation of novel lectin-mediated molecular mechanisms of cell-cell or cell-extracellular matrix (ECM) interactions that modulate IR signaling in T2D. This knowledge will be fundamental to opening up new carbohydrate-based approaches to T2D treatments.

We have successfully completed Phase 1 studies. In studies with cells, GAL3 inhibited IR/IRS-1 activation, which was reversed by TFD100. In high-fat diet (HFD) animal model, TFD100 treatment significantly improved glucose tolerance and insulin tolerance compared to the vehicle-treated animals.

After analyzing our results, we are excited to continue our drug development. TFD100 is a biologic drug and we believe that TFD100 will likely be distributed as a solution in the prefilled cartridge to be taken by T2D patients at home, similar to non-invasive SC injection of insulin or Ozempic.

To enhance the scientific rigor, we plan to ascertain SC administered TFD100's ability to treat T2D in HFD model, and to complete relevant IND-enabling experiments in the following specific aims: 1) determine PK/PD of TFD100; 2) ascertain efficacy of SC administered TFD100 to treat HFD-induced obesity, insulin resistance, and T2D; and 3) GLP production of TFD100 for future toxicology studies.

The proposed activities will be either performed by expert contractual collaborators or will be guided by an exceptional consultant team with specialized industry expertise in biologics product development, regulation, and clinical development. The outcomes of these studies will lead to the submission of IND to the FDA followed by a Phase 1 clinical trial.

Glycomantra

NOT APPLICABLE

93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHS - NIH]

Halethorpe, Maryland 212273863 United States

Single Zip Code

PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-22-176)

Amendment Since initial award the total obligations have increased 103% from $1,810,483 to $3,674,654.