West Coast Editor

ThromboGenics NV's licensing deal with Rhein Minapharma Biogenetics for preclinical THR-174 could bring a next-generation thrombolytic for developing countries, a cheaper therapy for heart attacks that's equivalent to the gold standard tissue plasminogen activator (tPA).

In return for the license, Leuven, Belgium-based ThromboGenics gets upfront and milestone payments, along with double-digit royalties, with Rhein Minapharm, a subsidiary of Minapharm SAE, of Cairo, Egypt, paying all future costs.

THR-174 - a recombinant form of staphylokinase, the enzyme from Staphylococcus aureus that catalyzes the conversion of plasminogen to plasmin - is targeted to launch by 2010, and could replace streptokinase, the most widely used heart-attack therapy in poorer countries.

Streptokinase's side effects and immunogenic responses have not been evident so far with THR-174, which means the drug could be given repeatedly without the use of steroids to less allergic reactions. What's more, physicians can inject THR-174 as a single bolus or double bolus, or can infuse the drug continuously, depending on need.

The arrangement covers the Middle East and North Africa or 360 million people, about the population of the EU.

ThromboGenics will transfer its THR-174 technology to Rhein Minapharm, which will manufacture the drug. Rhein Minapharm will be responsible for developing the commercial manufacturing process, implementing a clinical development plan, and gaining marketing clearance.

Late last year, ThromboGenics struck a deal related to another staphylokinase thrombolytic, THR-100, with Bharat Biotech International Ltd., of Hyderabad, India. The drug carries similar benefits to THR-174, and details disclosed about the Bharat licensing deal resemble those in the arrangement with Rhein Minapharm.

Programs in the clinic at ThromboGenics include microplasmin, in Phase II testing for vitreoretinal disorders and as a thrombolytic agent for occlusive diseases, and TB-402 (anti-Factor VIII), set to enter a Phase II study next year in collaboration with Bioinvent International AB, of Lund, Sweden. Last month, added €5.1 million (US$7.2 million) to its coffers through the exercise of 1.1 million warrants, increasing the outstanding shares to 25.5 million.

The failure-strewn hunt goes on for better thrombolytics in various settings. In late August, New York-based Forest Laboratories Inc. backed out of developing Paion AG's stroke drug desmoteplase before analysis was complete of the fizzled Phase III trial, and returned North American rights to Paion, of Aachen, Germany. (See BioWorld Today, Aug. 31, 2007.)

Earlier the same month, San Carlos, Calif.-based Nuvelo Inc. restarted its derailed alfimeprase program, enrolling patients in the previously discontinued SONOMA-3 trial testing the compound in treating central venous catheter occlusion. Nuvelo is trying a higher dosage than the failed SONOMA-2 Phase III trial in the same indication. The December setback was accompanied by the failure of alfimeprase in a separate Phase III trial in acute peripheral arterial occlusion. Nuvelo's alfimeprase partner, Bayer Healthcare AG, has since bailed out. (See BioWorld Today, Aug. 23, 2007.)

Another, somewhat different approach also making news in August belongs to ImaRx Therapeutics Inc., of Tucson, Ariz., which went ahead with the second dose cohort in its Phase I/II trial combining SonoLysis therapy with tPA in ischemic stroke patients. SonoLysis therapy combines ImaRx's MRX-801 microbubbles with ultrasound to break up blood clots and restore blood flow to tissues. The dose-escalation trial started in January and is expected to complete enrollment of its target 72 patients in the first half of next year.