Presentation Abstract

Program#/Poster#: 185.6/DD23
Title: ANG1005: Development of a new Engineered Peptide Compound (EPiC) for the treatment of malignant glioma
Location: South Hall A
Presentation Time: Sunday, Oct 18, 2009, 9:00 AM -10:00 AM
Authors: J. DRAPPATZ1, A. BRENNER2, S. ROSENFELD3, D. SCHIFF4, P. WEN1, T. MIKKELSEN5, M. GROVES6, E. T. WONG7, A. EICHLER8, K. M. ELIAN9, B. LAWRENCE9, *M. DEMEULE9, J.-P. CASTAIGNE9;
1Dana-Farber Cancer Inst., Boston, MA; 2Cancer Therapy and Res. Center, UT Hlth. Sci. Ctr. San Antonio, San Antonio, TX; 3Columbia Universtiy Med. Ctr., New York, NY; 4Univ. of Virginia Hlth. Syst., Charlottesville, VA; 5Henry Ford Hlth. Syst., Detroit, MI; 6MD Anderson, Houston, TX; 7Beth Israel Deaconess Med. Ctr., Boston, MA; 8Massachusetts Gen. Hosp., Boston, MA; 9Angiochem Inc., Montreal, QC, Canada
Abstract: Introduction: Malignant glioma (MG) is an aggressive and fatal cancer whose treatment is limited by the inability of drugs to cross the BBB. Angiochem is developing a deep and broad product pipeline of new breakthrough drugs that are uniquely capable of crossing the BBB to treat brain diseases. ANG1005, the first product created from the Engineered Peptide Compound (EPiC) platform, is a novel taxane derivative. Studies show that ANG1005 enters the brain by targeting low-density lipoprotein receptor-related protein (LRP); one of the most highly expressed receptors on the BBB, and also enters tumor cells via LRP, which is upregulated in various cancer cells including MG cells.
Methods: As of 18-May-2009, 37 patients with recurrent/progressive WHO Grades III-IV MG have received ANG1005 by IV infusion at doses of 30-550 mg/m2 once q21d without premedication. Study objectives include characterizing the safety/tolerability, identifying the MTD and obtaining preliminary PK and antitumor information in patients with MG. Drug penetration into extracted MG tumors was measured in a sub-group of patients undergoing debulking surgery following a single dose of ANG1005.
Results: Dose escalation is ongoing. At doses evaluated thus far, few, if any, patients have experienced neutropenia, leucopenia, thrombocytopenia, anemia, infusion reactions, mucositis or peripheral neuropathy at a severity ≥ Grade 2 (CTCAE, v.3). Neurocognitive data show that ANG1005 does not cause CNS toxicity at these doses. Biological data show that ANG1005 does not elicit an immune response even in patients who have received multiple treatment cycles. MRI data indicate potential efficacy in tumor regression/slowing tumor progression. Pharmacokinetic data show a linear relationship between dose and bioavailability. Data from extracted tumors (n=3) showed that ANG1005 uptake was 20-40x greater than reported following an equivalent dose of paclitaxel; and ANG1005 concentration in tumor relative to blood exceeded 25%.
Conclusion: Data to date demonstrate that ANG1005 has an excellent safety/tolerability profile, penetrates into tumors and shows promise as a potential treatment option for patients with recurrent/progressive MG.
Disclosures:   J. Drappatz, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); A. Brenner, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); S. Rosenfeld, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); D. Schiff, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); P. Wen, Angiochem Inc., F. Consultant/Advisory Board; T. Mikkelsen, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); M. Groves, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); E.T. Wong, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); A. Eichler, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); K.M. Elian, Angiochem Inc., A. Employment (full or part-time); B. Lawrence, Angiochem Inc., A. Employment (full or part-time); M. Demeule, Angiochem Inc., A. Employment (full or part-time); J. Castaigne, Angiochem Inc., A. Employment (full or part-time).
Keyword(s): ANG1005
Malignant Glioma
Glioblastoma Multiforme
[Authors]. [Abstract Title]. Program No. XXX.XX. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.

2009 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.




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