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GL1001

Ore Pharmaceuticals is seeking a partner for GL1001, a novel, clinical stage, potent and highly selective inhibitor of the carboxypeptidase, ACE2. The molecule possesses a desirable therapeutic profile including:

  • First-in-class small molecule
  • Orally administered
  • Well tolerated in man
  • Excellent preclinical safety profile PK consistent with once daily dosing
  • Efficient, simple 5-step chemical synthesis
  • IND filing anticipated: Summer 2008
  • Several potential therapeutic uses (i.e., ulcerative colitis, Crohn’s disease, non-ulcer dyspepsia, gastric ulcer, esophagitis, chronic pancreatitis)

GL1001 Development
GL1001 is a nanomolar inhibitor of the ACE2 enzyme, whose substrates include products of angiotensinogen and apelin, which is involved in intestinal epithelium repair in colitis. Ore Pharmaceuticals broadly analyzed GL1001’s action in vivo and in vitro as well as its disease-specific expression in over 20,000 human tissue samples. ACE2 is highly expressed in the gastrointestinal tract. Of more than 400 diverse disease states examined, ACE2 was modulated in only two conditions, chronic gastritis and chronic pancreatitis. In vivo animal data demonstrated that GL1001 inhibited NF-ĸB pathway activity in some GI organs, suggesting tissue-specific anti-inflammatory activity. In vivo models provided compelling evidence that GL1001 reduces signs of injury and inflammation in experimental colitis, gastritis and gastric ulcer. In the mouse dextran sodium sulfate (DSS) model, GL1001 dose-dependently reduced signs of disease activity, reduced severity of histological lesions, and achieved high concentrations selectively in the tissues of the colon. GL1001 reduced gastric damage scores and myeloperoxidase activity in rat models of injury induced by non-steroidal anti-inflammatory drugs. Additional testing in alternative animal models of IBD, gastritis, and esophagitis is underway. GL1001 has completed testing in a clinical Phase I single-ascending dose study in the U.K. It was well-tolerated up to the highest dose tested (2100 mg) which is consistent with results of animal toxicity and safety studies. GL1001 has a pharmacokinetic profile consistent with once daily dosing. An IND is in preparation so that a planned 2008 clinical trial may enroll subjects in the United States.

 

Intellectual Property
Ore Pharmaceuticals has an exclusive license to the target inhibitor composition-of-matter (COM) patents – issued in the U.S. in October 2003 and May 2006 - in all fields of use excluding oncology. The patent estate is fortified by recent patent applications claiming methods of using the COM for gastrointestinal disease indications and an exclusive license to related target-inhibitor patents useful for the expanded development of GL1001.

 

Partnering Opportunities
Ore Pharmaceuticals seeks to out-license or co-develop repositioned drug candidates in our proprietary drug development pipeline and we welcome discussions with interested pharmaceutical and biotechnology companies.

 

For further information on this opportunity, please contact:
Deborah Barbara
Vice President, Business Development & Licensing
240-491-7750
dbarbara@orepharma.com
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