Potent Topoisomerase I Inhibition For Glioma Therapy

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: PHS2001-2
Agency Tracking Number: 1R41CA091700-01
Amount: $133,125.00
Phase: Phase I
Program: STTR
Awards Year: 2001
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (859) 257-2300
Business Contact
Phone: (606) 257-2300
Research Institution
 Nonprofit college or university
DESCRIPTION (PROVIDED BY APPLICANT): DB-67 is a promising new silatecan (silylcamptothecin) analog that displays superior blood stability relative to the FDA-approved camptothecin congeners, topotecan and CPT- 11. DB-67 also exhibits a high degree of anti-cancer potency both in vitro and in vivo. DB-67 is a highly lipophilic camptothecin and active lactone levels persist in human tissues to a much greater degree than existing FDA-approved camptothecins. DB-67 has been shown by Pollack et al. to be more potent than other camptothecins against glioblastoma cells; in the same study the agent was found to be highly effective against intracranially implanted glioblastoma tumors. For this Phase I application there are two key issues that will be addressed. First, liposomal formulation studies are required as DB-67 is highly lipophilic and may crystallize at the site of injection unless properly formulated. Thus, we intend to develop a lyophilized liposomal DB-67 preparation that displays ideal stability and microemulsion characteristics upon re-suspension. Secondly, we will test our lead liposomal formulations in a human glioma xenograft murine model system to ensure that the DB-67 formulations exhibit the predicted efficacy profile. DB-67 has already been well explored in vitro and in vivo; thus, the intent of this Phase I application is to find the best formulation for advancing DB-67 to clinical trials by thoroughly studying various liposomal formulations. PROPOSED COMMERCIAL APPLICATION: Initial FDA approval of comptothecins (topotecan and CPT-11) occurred in 1996. In 1998 their use was expanded by the FDA for new indications. With other campthecins currently in clinical development, a worldwide market of approximately 1 billion dollars is anticipated in the near future. Our novel, blood-stable camptothecin, DB-67, described in this application may present several therapeutic advantages over the campthecin drugs that are currently used and, accordingly, could eventually control a significant portion of the campthecin market.

* Information listed above is at the time of submission. *

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