Partners

ThromboGenics and BioInvent entered into a license agreement with Roche for their jointly developed anticancer agent TB-403. TB-403 is a novel monoclonal antibody that blocks placental growth factor (PlGF), one of the growth factors responsible for the development of new blood vessels.

Under the terms of the agreement, ThromboGenics and BioInvent received an upfront payment of €50 million. In addition, ThromboGenics and BioInvent could potentially receive up to €450 million over the term of the collaboration based on the successful completion of a series of development and commercial milestones for multiple indications, as well as double-digit royalties on potential product sales, including any backup antibodies based on inhibition of PlGF. ThromboGenics, which discovered TB-403, will receive 60% and BioInvent 40% of the revenue from the deal. Roche will have a worldwide, exclusive license to develop and commercialize TB-403. ThromboGenics and BioInvent will retain copromotion rights for the product in the Benelux, Baltic, and Nordic regions.

TB-403 has the potential to be a major advance in the treatment of cancer. It is a humanized monoclonal antibody that blocks the formation of the new blood vessels that are needed by solid tumors to support their growth. TB-403 has the potential to minimize both the growth and spread of cancer cells.

ThromboGenics and Bharat Biotech International Limited entered into a license agreement for manufacturing, clinical development, and commercialization of THR-100 (formerly known as Sak42D), a novel variant of recombinant staphylokinase, in developing countries and certain industrialized countries. THR-100 is a thrombolytic agent developed for treatment of AMI and other vascular diseases based on its ability to dissolve blood clots. In return for granting this license, we will earn double-digit royalties on net sales. Bharat Biotech will assume responsibility for all future costs.

Bharat Biotech has initiated a Phase III trial in India with THR-100 in patients suffering an AMI.  The results of this trial will pave the way for this novel thrombolytic to be filed for marketing approval by Bharat with Indian regulatory authorities.

THR-100 has completed phase 2 clinical trials in Europe for treatment of AMI in more than 140 patients. In the clinic, THR-100 has demonstrated efficacy equivalent to tissue plasminogen activator (tPA), considered the “gold standard” for thrombolytic therapy, but at significantly lower patient cost than tPA. THR-100 has also shown superior efficacy to both streptokinase and urokinase, the most commonly used thrombolytic agents in the developing world for the treatment of AMI and other thrombotic conditions.

The objective of the agreement between ThromboGenics and Bharat Biotech is to develop and commercialize THR-100 as a replacement for established thrombolytics, such as streptokinase and urokinase, in developing markets. As part of this license deal, we will transfer our THR-100 technology to Bharat Biotech, which will become the global manufacturer for the finished drug. With our input, Bharat Biotech will be responsible for developing the commercial manufacturing process, implementing a clinical development plan for phase 3 trials, and gaining marketing authorization to commercialize THR-100, initially in India. Entry into markets outside of India is also planned as part of this alliance.

ThromboGenics and Rhein Minapharm entered into a license agreement for manufacturing, clinical development, and commercialization of THR-174, the next-generation derivative of staphylokinase, in the Middle East, Africa, and other countries comprising the MENA region. THR-174 is a recombinantly derived thrombolytic agent developed for treatment of acute myocardial infarction (AMI; heart attack). In return for granting this license, we will receive upfront and milestone payments and will earn double-digit royalties on net sales. Rhein Minapharm will assume responsibility for all future costs.

In preclinical studies, THR-174 has shown improved efficacy, safety, and, most importantly, reduced immunogenic response compared to earlier versions of staphylokinase, as well as to established thrombolytics, such as streptokinase. Unlike streptokinase and other therapies, THR-174 produces a lower antibody response or allergic reaction. This means that it could potentially be administered to most patients more than once, allowing treatment of subsequent cardiac events and improving quality of care, with minimal side effects and without the use of steroids.

The agreement between ThromboGenics and Rhein Minapharm is designed to develop and commercialize THR-174 as a replacement for established thrombolytics, such as streptokinase, in the Middle East, Africa, and other countries. As part of this license deal, we will transfer our THR-174 technology to Rhein Minapharm, which will manufacture the finished drug. With our input, Rhein Minapharm will be responsible for developing the commercial manufacturing process, implementing a clinical development plan, and gaining marketing authorization to commercialize THR-174 in the Middle East, Africa, and other countries.

ThromboGenics and BioInvent International AB entered into a collaborative research and licensing agreement in September 2004 to co-develop antibody-based drugs for vascular indications. Currently, we are jointly developing 2 candidates:

• TB-402 (anti-factor VIII) as an anticoagulant therapy for numerous indications, including prevention and treatment of deep vein thrombosis and treatment of atrial fibrillation
• TB-403 (anti-PlGF) as an antiangiogenic agent for potential treatment of various diseases, including cancer, age-related macular degeneration, retinopathies, and inflammation

The objective of this collaboration is to bring together a portfolio of expertise in the area of antibody discovery, development, and manufacturing. BioInvent contributes its knowledge and experience in antibody discovery, production, and immunology, and we contribute our research and clinical development skills in the area of vascular medicine. Both parties provide core intellectual property based on specific therapeutic targets.

ThromboGenics and Millipore Corporation entered into a license agreement under which we have licensed our technology for production of the proprietary stem cell culture medium marketed by Millipore as RESGRO™*. The technology for producing RESGRO was originally developed by our drug discovery team as part of our successful efforts to identify several of our drug discovery candidates currently in clinical trials.

ThromboGenics, along with our partner Geymonat, has entered into 2 co-exclusive licensing agreements, with Roche Diagnostics and Biosite Inc., for use of PlGF in diagnostic applications. ThromboGenics and Geymonat have out-licensed the use of PlGF as a diagnostic marker for the prediction of major cardiac events, such as heart attack, and preeclampsia, a disease of pregnancy. ThromboGenics and Geymonat received upfront payments upon signing these agreements and will receive milestone payments tied to submission to regulatory authorities and approval for commercialization, as well as royalties on net sales.

Center For Molecular and Vascular Biology, KULeuven

ThromboGenics has collaborations on projects that are in-licensed from this academic center, including the development of staphylokinase and Anti-Factor VIII.

Prof Dr Peter Verhamme
In addition to the above collaborations, ThromboGenics has Advisory Boards for several of our advanced programs (namely the Anti-Factor VIII Advisory Board and the Anti-PlGF Advisory Board).

Prof Dr Peter Carmeliet
ThromboGenics has an ongoing collaboration with the Center for Transgene Technology and Gene Therapy, a department of the VIB, on the preclinical characterization of 2 of its programs that were in-licensed from this institute, anti-PlGF and PlGF.