Shal Technologies, Inc. — Department of Health and Human Services SBIR Phase II: NCI

Description

DESCRIPTION provided by applicant The goal of this SBIR proposal is to complete the majority of the pre clinical studies and testing needed to submit an IND application and advance a promising new therapeutic for non Hodgkinandapos s lymphoma SH into a clinical trial SH is a selective high affinity ligand SHAL that was designed to target a unique site on HLA DR a protein receptor found on the surface of B cell lymphocytes and overexpressed in many B cell derived lymphomas and leukemias SH binds selectively and is highly cytotoxic at pM concentrations only to tumor cells expressing HLA DR In a Raji xenograft mouse model of animals treated with g kg of SH experienced a permanent cure that is the tumors disappeared within days after treatment and did not return during the remainder of the life of the animal In addition no adverse side effects have been observed in animals even when the dose was increased fold The specific aims proposed in phase II of this SBIR are to determine the potential impact of SH metabolism and metabolites on its function and the metabolism of other drugs confirm the mechanism of action of SH determine the pharmacokinetics toxicology and safety of SH in rodents and dogs and confirm SH selectivity for B cell malignancies and identify the potential breadth of the SH indication Upon the successful completion of this Phase II project SHAL Technologies will use the results to identify any additional tests that need to be conducted prepare and submit an IND application open a Phase I clinical trial and move forward with the clinical evaluation of SH as a new therapeutic for treating and potentially curing advanced non Hodgkinandapos s lymphoma and other B cell derived forms of cancer If successful this effort will provide a more effective first line therapy for advanced NHL Fewer side effects would be expected because only those cells that are overexpressing HLA DR are targeted and killed normal cells are not affected SH a biotinylated analog of SH could be used as companion diagnostic to identify those patients for whom this treatment would be most likely to be effective Radionuclide tagged SH may also prove useful as an imaging agent to monitor the progression of the patientandapos s disease The low cost of SH synthesis should reduce the cost of NHL therapy significantly and make the drug available to all those diagnosed with NHL PUBLIC HEALTH RELEVANCE There is a public health need to develop more efficacious less toxic and more cost effective treatments for advanced cancers This project addresses this need by proposing the studies and testing that must be completed to advance into clinical trials a promising new targeting agent and therapeutic for patients with non Hodgkinandapos s lymphoma which our current results suggest is remarkable and is likely to improve patient survival and reduce side effects and treatment costs significantly