SBIR-STTR Award

Enhancement of tumor targeting and chemotherapeutic ac*
Award last edited on: 7/5/07

Sponsored Program
SBIR
Awarding Agency
NIH : NCI
Total Award Amount
$1,874,713
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Christopher P Leamon

Company Information

Endocyte Inc

3000 Kent Avenue Suite A1-100
West Lafayette, IN 47906
   (765) 463-7175
   info@endocyte.com
   www.endocyte.com
Location: Single
Congr. District: 04
County: Tippecanoe

Phase I

Contract Number: 1R43CA096020-01
Start Date: 00/00/00    Completed: 00/00/00
Phase I year
2002
Phase I Amount
$250,000
The objective of this proposal is to advance the development of a novel tumor- targeted antineoplastic drug conjugate. Our concept is based on the use of the vitamin folate to deliver a potent, covalently-attached chemotherapeutic drug to folate receptor (FR)-positive tumors in vivo and to potentiate a greater anti-tumor response in syngeneic animal models relative to that obtained with the un-conjugated drug. It is well-known that many types of human cancers vastly over-express FR and that folate-macromolecule conjugates specifically bind to and enter FR-expressing tumor cells via an endocytosis mechanism. Importantly, internalized folate-drug conjugates are exposed to both acidic and reducing environments within these intracellular endocytic compartments. Thus, high therapeutic efficacy may result from the use of potent folate-drug conjugates constructed with endosome-labile linkers. As such, the following specific aims are proposed: i) synthesize a novel acid- cleavable folate-drug conjugate, ii) synthesize a related thiol-labile folate- drug conjugate, iii) conduct in vitro dose-response cytotoxicity studies, and iv) conduct an initial therapeutic animal study with the more potent folate- drug conjugate. Following the completion of these specific aims, a Phase II project will be initiated which will include the submission of a corporate IND application for a folate-drug conjugate to the FDA and the initiation of an IND Phase I clinical study.

Thesaurus Terms:
antineoplastic, chemical conjugate, drug design /synthesis /production, drug screening /evaluation, folate, mitomycin chemical synthesis, cytotoxicity, endocytosis, thiol

Phase II

Contract Number: 2R44CA096020-02A1
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2004
(last award dollars: 2006)
Phase II Amount
$1,624,713

The objective of this Phase II SBIR grant is to advance the development of EC72, a novel folate-targeted drug conjugate that can safely deliver covalently attached mitomycin C (MMC) specifically to folate receptor (FR)-positive tumors in vivo. EC72 offers a number of advantages over standard chemotherapy agents. It is small (mw = 937), highly water soluble, tumor-targetable (via folate), and capable of releasing the active MMC drug upon entry into the target cell by an endocytic process. Plus, recent data strongly indicate that EC72 is not toxic to major organs, including the FR-positive kidneys and the bone marrow, and it can also manifest synergistic anti-proliferative activity in vivo when dosed in combination with Taxol. To facilitate the continued development of EC72, the following six Phase II specific aims are proposed: (1) determine EC72's pharmacokinetic tissue distribution, metabolism and excretion profile in mice as well as serum protein binding properties, (2) conduct additional pre-clinical pharmacology studies in mice to correlate therapeutic efficacy with respect to the tumor's net folate receptor expression level, (3) complete GLP toxicology studies required by the FDA to support Phase I clinical trials, (4) validate an LC/MS/MS method for measuring EC72 levels in human serum, (5) manufacture cGMP-grade drug products and conduct stability testing, and (6) submit an IND for EC72