SIGNABLOK, INC. — Department of Health and Human Services SBIR Phase I: 100

Description

DESCRIPTION provided by applicant Carcinoma of the pancreas or pancreatic cancer PC is the fourth leading cause of cancer related death in the United States According to the American Cancer Society new cases and deaths are expected in Despite advances in therapy the year survival rate is less than Current treatments of PC include surgery radiation therapy chemotherapy and immunotherapy but they all only slightly prolong survival or relieve symptoms in patients with PC The limitations in efficacy of available treatments highlight the need for new treatments Pancreatic inflammation is known to increase the risk of PC High macrophage infiltration into the tumor mass correlates with the promotion of tumor growth and metastasis development As found recently triggering receptor expressed on myeloid cells TREM an inflammation amplifier plays a role in PC progression Expression of TREM on myeloid cells including tumor associated macrophages TAMs in patients with PC is upregulated and correlates to disease severity We hypothesize that TREM inhibition can improve survival of PC patients Current approaches to TREM suggest to block binding of ligand to TREM The true nature of the TREM ligand is not yet known highly increasing the risk of failure of these approaches in clinical development The long term objective of the proposed project is to develop a novel ligand independent approach to a TREM targeted treatment of PC The major goal of the Phase I study is to demonstrate that specific inactivation of TREM with novel inhibitory peptides suppresses PC tumor progression in animal model system and improves survival Phase I specific aims are to generate and characterize injectable formulations of TREM inhibitory peptides with different half lives and test the TREM inhibitory peptide formulations in a mouse model of PC The peptides will be designed using SignaBlokandapos s proprietary model of TREM signaling These non toxic peptides employ novel ligand independent mechanisms of action and are anticipated to have less severe side effects In order to increase peptide solubility bioavailability and targeting to TAMs we will utilize SignaBlokandapos s proprietary nanosystem for macrophage targeted delivery of water insoluble and poorly water soluble drugs We will use a BxPC xenograft mouse model of PC to test the ability of the peptides in free and particulate forms to inhibit cancer progression and promote survival It is anticipated that the proposed research will identify novel anticancer lead compounds that will set the stage for the development of new targeted therapies of PC thereby leading to a higher survival rate of the patients If successful the Phase I will be followed in te Phase II by toxicology absorption disposition metabolism excretion ADME pharmacology and chemistry manufacturing control CMC studies filing an Investigational New Drug IND application with the US Food and Drug Administration FDA and subsequent evaluation in humans Importantly TREM may play a role in the progression of not only PC but also other tumors Thus successful completion of Phase I will provide the proof of concept of the hypothesis that might be applicable to a variety of tumors PUBLIC HEALTH RELEVANCE Pancreatic cancer is the fourth leading cause of cancer related death in the United States and the year survival rate is less than Current treatments are substantially ineffective and only slightly prolong survival or relieve symptoms in the cancer patients The proposed research is expected to result in the development of novel anticancer therapeutics that could substantially improve treatment of this type of cancer thereby leading to a higher survival rate of the patients