Navidea Biopharmaceuticals, Inc. — Department of Health and Human Services SBIR Phase I: NIAMS

Description

DESCRIPTION provided by applicant Navidea Biopharmaceuticals is seeking SBIR Fast Track grant support for preclinical animal studies and a regulatory phase clinical study of the ability of mTc tilmanocept to identify skeletal joint inflammation due to rheumatoid arthritis RA RA is a chronic progressive systemic autoimmune disease characterized by skeletal joint inflammation If not treated successfully RA can lead to disability disfigurement and premature death Recently antirheumatic drugs DMARDs have dramatically improved outcomes for many RA patients Three problems persist DMARDs are most effective when RA symptoms first appear which is problematic for current RA diagnostics monitoring the effectiveness of DMARD therapy is challenging and a significant portion of RA patients respond poorly or not at all to current DMARDs Therefore there are significant unmet medical clinical needs for a more accurate RA diagnostic especially for early stage RA and for more effective RA therapies With this application Navidea is initiating efforts intended to address these clinically pivotal needs mTc Tilmanocept is a wholly synthetic molecule designed specifically to bind with high affinity to macrophage mannose receptors CD The original intended use for mTc tilmanocept was for imaging sentinel lymph nodes during cancer surgeries an indication for which mTc tilmanocept has received FDA approval mTc Tilmanocept binds to CD displayed on macrophages residing in tumor associated lymph nodes In RA large numbers of CD expressing macrophages infiltrate into the synovial spaces of inflamed joints An animal study with a mouse model of RA showed that mTc tilmanocept can be injected intravenously and thereafter accumulates specifically in RA inflamed joints In an ex vivo test of human synovial aspirates Cy tilmanocept strongly differentiated RA from osteoarthritis and healthy control tissue In this application additional animal studies are proposed to ensure the safety of injecting mTc tilmanocept intravenously Then in a clinical study mTc tilmanocept will be injected intravenously into four types of study participants participants with active RA participants with recent development of polyarthralgia PAT healthy arthritis free individuals over the age of and patients with painful joints not caused by RA PAT may have many causes of which RA is only one About of PAT patients are expected to progress to frank RA in yr It is the RA patients among these patients that would benefit m o s t from early diagnosis so that they can receive DMARD therapy when it is most effective Participants injected with mTc Tc tilmanocept will be imaged by single photon emission computed tomography SPECT This study will investigate the ability of mTc tilmanocept to identify RA inflamed joints and to identify early RA patients among those with PAT Follow on studies will investigate if tilmanocept can also target delivery of therapeutics to RA inflamed joints thus enabling better therapies PUBLIC HEALTH RELEVANCE This project seeks to significantly improve patient outcomes and quality of care for patients with rheumatoid arthritis by providing these patients with an innovative targeted agent tilmanocept that provides more accurate and more timely earlier diagnosis of their illnesses This will enable currently available therapeutics to be more effectiv and may make possible the development of new and even more effective therapies based on the targeted diagnostic