NU172
How NU172 Works |
Potential Therapeutic Applications |
Clinical Trials |
Commercialization Rights | Scientific Publications and Presentations
A Thrombin Inhibitor
NU172 is a short-acting aptamer designed to directly inhibit thrombin's ability to stimulate blood clot formation. Preclinical and clinical studies suggest that NU172 has the potential for predictable anticoagulant properties with rapid onset and offset of action. Due to its short half-life, the effect of NU172 is rapidly reversed without the need for an antidote.
How NU172 Works
NU172 is an aptamer, a single-stranded nucleic acid that forms a well-defined three-dimensional shape conceptually similar to an antibody. Aptamers combine the optimal characteristics of small molecules and antibodies, including high specificity and affinity, and the ability to target protein-protein interactions. In contrast to monoclonal antibodies, aptamers are chemically synthesized rather than biologically expressed.
Potential Therapeutics
NU172 is being studied as a potential short-acting anticoagulant for use in the setting of medical or surgical procedures such as coronary artery bypass graft (CABG) surgery, percutaneous coronary interventions (PCI) and kidney dialysis. Approximately 450,000 CABG procedures, 1.2 million PCIs and more than 50 million dialysis procedures are performed annually in the U.S. During these procedures, anticoagulants are given to prevent blood clotting, but must be reversed once the procedure has been completed in order to prevent excessive bleeding. Current standard of care for these procedures is anticoagulation with heparin, followed by protamine to reverse the anticoagulation once the procedure is complete.
Clinical Trials
We recently completed a Phase 1 proof-of-concept trial examining the safety, tolerability and pharmacokinetics of escalating single bolus doses of NU172 in 30 healthy volunteers. In the trial, NU172 produced dose-dependent increases in anticoagulation, measured by activated clotting time (ACT); rapid onset and offset of anticoagulation with an average peak ACT of 415 seconds; and a rapid return toward baseline upon drug discontinuation. NU172 was well-tolerated and no serious adverse events were reported.
In June 2008, we began a Phase 1b trial to determine the safety, tolerability and pharmacokinetics of bolus plus escalating infusion doses of NU172 in approximately 30 healthy male volunteers. The escalating infusion doses will be given for up to four hours, mimicking the drug's potential administration in CABG surgery. We expect top-line data from this trial in the third quarter of 2008. If the data from the Phase 1b trial are consistent with the results from the initial Phase 1 trial, a Phase 2 trial would begin in the fourth quarter of 2008 or the first quarter of 2009.
Commercialization Rights
In August 2006, we entered into a worldwide collaboration with Archemix to develop and commercialize anti-thrombin aptamers. Under the terms of the agreement, Archemix is responsible for discovery of short-acting aptamers for use in acute cardiovascular procedures, and Nuvelo is responsible for development and worldwide commercialization of these aptamers. We paid Archemix an up-front payment of $4.0 million and, under certain circumstances, may invest up to $10.0 million in Archemix's common stock upon an initial public offering. We also agreed to fund Archemix research in the area of short-acting aptamers for three years at a minimum of $5.25 million. In addition, Archemix may receive payments totaling up to $35.0 million per development compound on the achievement of specified development and regulatory milestones, along with potential royalty payments based on sales of licensed compounds. At the initiation of the first Phase 3 study for any licensed compound, Archemix has the option to elect to participate in profits from sales of the compound by funding its pro rata share of prior and future product development and commercialization expenses, in lieu of receiving milestone payments and royalties with respect to that compound.
Scientific Publications
Scientific Presentations
Wagner-Whyte J, Khuri S, Olsen K, Hatala P, Boomer RM, Fraone JM, Brosnan N, Makim A, Lewis SD, Cai L, McCauley T, Hutabarat R, Horvath C, Ganley K, Funk W, Deitcher S, Treanor P, Thatte H, Hussaini BE, Rottman JB, Diener JL. Discovery of an extremely potent aptamer direct thrombin inhibitor. International Society on Thrombosis and Haemostasis (ISTH) Annual Meeting, July 2007, Geneva, Switzerland. [Wagner-White J et al J Thromb Haemost 2007;5(Suppl 1):Number P-S-067.]
Hutabarat RM, McCauley T, Makim A, Lewis S, Olsen K, Wagner-Whyte J, Diener J, Matyugicheva U, Scull J, Levy MD, Deitcher SD, Funk WD, Bouchard P. Pharmacokinetic/pharmacodynamic profile of a novel aptamer direct thrombin inhibitor in cynomolgus monkeys and Yorkshire pigs following a single IV bolus administration. International Society on Thrombosis and Haemostasis (ISTH) Annual Meeting, July 2007, Geneva, Switzerland. [Hutabarat RM et al J Thromb Haemost 2007;5(Suppl 2): P-S-072.]