Phase I Clinical Trial Of Anticoagulant TB-402 Successfully Completed

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ThromboGenics NV, BioInvent International have successfully completed enrollment and initial follow-up of all volunteers in the first Phase I trial of TB-402, which is being developed for the prevention of venous thromboembolic disorders (VTE - blood clots).

TB-402 is a recombinant human monoclonal antibody that targets factor VIII, a component of the coagulation cascade. This antibody is a promising novel anticoagulant agent particularly because it only partially inhibits factor VIII activity even when administrated in very high doses. This may potentially decrease the risk of undesirable bleedings and the need for monitoring, which are the main concerns associated with anticoagulants currently on the market.

The trial, performed in Denmark, was a randomized, single-dose, placebo-controlled, dose-escalation trial in healthy male volunteers. 56 volunteers were enrolled into the trial, including both younger age volunteers (18-45) and older age volunteers (55-76).

Preliminary results of the trial showed that TB-402 met both the primary (safety and tolerability) and secondary (pharmacokinetic and pharmacodynamic) endpoints. The drug was well tolerated and the study showed that TB-402's prolonged half-life will allow for single-dose treatment in orthopaedic surgery patients and/or once-a-month administration for long-term stroke prevention in atrial fibrillation (AF), as opposed to daily treatment with current anticoagulants. Importantly, the findings confirm that TB-402 achieves only partial inhibition of factor VIII activity without the undesired effect of total factor VIII inactivation. Final data analysis of the first Phase I trial will be available later this year.

Based on these results, and after a review of preliminary results with the Scientific Advisory Board for this program, the Joint Steering Committee of ThromboGenics and BioInvent has decided to move TB-402 into Phase II clinical development. As part of the development programme, drug interaction studies will be performed in parallel with the preparation for Phase II, which is expected to start in H1 2008. The initial Phase II trial will be a dose-ranging clinical trial evaluating safety and efficacy (ability to prevent deep vein thrombosis - DVT) in an orthopaedic surgery setting.

Prof. Desire Collen, CEO of ThromboGenics, commenting on today's announcement, said: "We and our co-development partner, BioInvent, are extremely pleased to have completed the first TB-402 Phase I trial. Initial results of the trial are very encouraging and show that TB-402 is safe and has the potential to fill a significant unmet need in multiple major indications by allowing for single or once-monthly administration to prevent and treat debilitating and life-threatening conditions, such as deep vein thrombosis and stroke secondary to atrial fibrillation. We are looking forward to moving TB-402 into Phase II clinical trials in the first half of 2008."

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Svein Mathisen, CEO of BioInvent, added, "We are very satisfied that the trial has demonstrated that TB-402 is safe, and that it inhibits Factor VIII as predicted. The decision to advance into Phase II clinical development is once again evidence that our partnership is successful, proving the synergy of ThromboGenics' knowledge within vascular medicine and BioInvent's skills in antibody development."

Thromboembolic Disease

Thromboembolic diseases represent a major unmet medical need. The annual sales of anticoagulants (drugs that prevent blood clots) worldwide are over $5 billion. Nevertheless, available anticoagulants are still inconvenient and associated with a high risk of bleeding. Improved anticoagulants are therefore required. In particular, agents that allow for improved ease of administration (without requirement for daily dosing and frequent dose adjustment) would fill a significant unmet need.

Prevention and Treatment of Venous Thromboembolic disease (VTE)

Venous thromboembolic disease (deep vein thrombosis (DVT), pulmonary embolism) represents a major health issue, with an incidence of 1 to 3 per 1000 individuals per year and a high early mortality rate. One of the risk factors for VTE is major orthopaedic surgery. Anticoagulation prophylaxis is therefore indicated in this setting. In addition, in patients who develop a VTE, anticoagulation treatment for at least 6 months is indicated. Therefore, an agent allowing for once-a-month treatment in an outpatient setting is foreseen as an important option for the treatment of VTE.

Stroke Prevention in Atrial Fibrillation (AF)

Atrial fibrillation (AF), which is a strong risk factor for ischemic stroke, is the most common sustained arrhythmia observed in clinical practice. The prevalence of AF is estimated at 0.4% of the general population and increases with age, rising to 8.8% in the group aged 80-89 years. Given the aging population in the U.S. and other developed countries, the overall prevalence of AF is expected to continue to grow over the next several decades.

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