NOVATARG, INC. — Department of Health and Human Services SBIR Phase II: 200

Description

DESCRIPTION provided by applicant The present Phase SBIR application builds on the previous Phase SBIR award to identify a markedly improved biguanide to replace metformin in the treatment of T D Over new biguanides were synthesized in the Phase work and analyzed for their ability to produce metformin like activity in cells and animal models but at a much lower effective concentration The findings show that the aims of the Phase research were met by the generation of promising candidates that are more effective than metformin In the work proposed a limited number of new biguanides will be synthesized based on the structure function relationships identified in the Phase work These and the other novel biguanides in the NovaTarg library will be tested in cell and animal models of diabetes to understand their potential to treat this disease A preclinical candidate will be selected and advanced to GLP safety studies The results of this work will position the novel biguanide for an IND to treat T D The reason for conducting this drug discovery work lies in the inability of current drugs to treat T D and control the disease Unfortunately more than of affected individuals fail to achieve healthy blood glucose levels Of the therapies used metformin i e Glucophage a member of the biguanide drug class is the most prominent of the drugs as measured by the number of prescriptions issued worldwide Unfortunately up to of potential patients cannot tolerate this agent because of gastrointestinal adverse effects while another even larger segment of the diabetic population with renal insufficiency cannot take metformin because of the risk of lactic acidosis a life threatening condition generated by a decrease in metformin elimination by the kidney In the current application the preclinical candidate for an IND will be chosen for its ability to act on liver fat and skeletal muscle throug the OCT family of transporters and be excluded from the kidney Overall the agent should provide for better efficacy and less side effects Moreover the selection of this candidate will involve its ability to inhibit cancer cell proliferation an effect not optimized for metformin T has an increased risk for cancer development and our preclinical biguanide should protect against this feature of the disease better than any other drug category We believe that this is a unique aspect of our drug discovery program along with the increase in efficacy to lower blood glucose and reduce the side effects found with metformin Overall we expect that a much larger of the T D population will be able to use our drug and the efficacy on glucose control and on anti cancer effects will be much greater than that found for metformin PUBLIC HEALTH RELEVANCE NovaTarg Therapeutics has developed a drug discovery program to find an improved metformin the most prescribed drug worldwide for the treatment of T D The new treatment will accept more patients and be more efficient in controlling the symptoms of diabetes Importantly it will provide more protection against the development of cancer and overall this Phase ll SBIR program will fund the resources to identify the best biguanide to move into human clinical studies and fund the safety studies to support a successful IND application