99mTc-Tilmanocept for Targeting Rheumatoid Arthritis (RA)-Driving Macrophages

Information

  • Research Project
  • 9284732
  • ApplicationId
    9284732
  • Core Project Number
    R44AR067583
  • Full Project Number
    4R44AR067583-02
  • Serial Number
    067583
  • FOA Number
    PA-14-071
  • Sub Project Id
  • Project Start Date
    7/3/2015 - 9 years ago
  • Project End Date
    7/31/2017 - 7 years ago
  • Program Officer Name
    WITTER, JAMES
  • Budget Start Date
    8/1/2016 - 8 years ago
  • Budget End Date
    7/31/2017 - 7 years ago
  • Fiscal Year
    2016
  • Support Year
    02
  • Suffix
  • Award Notice Date
    7/26/2016 - 8 years ago
Organizations

99mTc-Tilmanocept for Targeting Rheumatoid Arthritis (RA)-Driving Macrophages

? DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals is seeking SBIR Fast Track grant support for preclinical animal studies and a regulatory phase 1/2 clinical study of the ability of 99mTc-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: 1 ] DMARDs are most effective when RA symptoms first appear, which is problematic for current RA diagnostics; 2 ] monitoring the effectiveness of DMARD therapy is challenging; and 3 ] 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. 99mTc- Tilmanocept is a wholly synthetic molecule designed specifically to bind with high affinity to macrophage mannose receptors (CD206). The original intended use for 99mTc-tilmanocept was for imaging sentinel lymph nodes during cancer surgeries, an indication for which 99mTc-tilmanocept has received FDA approval. 99mTc-Tilmanocept binds to CD206 displayed on macrophages residing in tumor associated lymph nodes. In RA, large numbers of CD206 expressing macrophages infiltrate into the synovial spaces of inflamed joints. An animal study with a mouse model of RA showed that 99mTc-tilmanocept can be injected intravenously and thereafter accumulates specifically in RA-inflamed joints. In an ex vivo test of human synovial aspirates, Cy3-tilmanocept strongly differentiated RA from osteoarthritis and healthy control tissue. In this application, additional animal studies are proposed to ensure the safety of injecting 99mTc-tilmanocept intravenously. Then in a clinical study, 99mTc-tilmanocept will be injected intravenously into four types of study participants: 12 participants with active RA, 30 participants with recent development of polyarthralgia (PAT), 12 healthy, arthritis free individuals over the age of 50, and 12 patients with painful joints not caused by RA. PAT may have many causes, of which RA is only one. About 2/3 of PAT patients are expected to progress to frank RA in =1 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 99mTc Tc-tilmanocept will be imaged by single-photon emission computed tomography (SPECT). This study will investigate the ability of 99mTc-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.

IC Name
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
  • Activity
    R44
  • Administering IC
    AR
  • Application Type
    4
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    1125665
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    846
  • Ed Inst. Type
  • Funding ICs
    NIAMS:1125665\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    NAVIDEA BIOPHARMACEUTICALS, INC.
  • Organization Department
  • Organization DUNS
    131891467
  • Organization City
    DUBLIN
  • Organization State
    OH
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    430177550
  • Organization District
    UNITED STATES