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Companies to advance mdm2/p53 inhibitors, which hold potential to address various tumor types
Munich, Ingelheim/Germany, 18 January 2010 - Boehringer Ingelheim and Priaxon entered into a worldwide collaboration to research and develop mdm2/p53 inhibitors for the treatment of cancer. Priaxon is providing its innovative and proprietary small molecule drug discovery expertise which is particularly suited to investigate inhibition of protein-protein interactions. p53 is a human tumor suppressor protein. It has been shown that in tumors with wild-type p53, the restoration of p53 tumor-suppressive functions can be achieved by blocking a cellular interaction of mdm21 and p53. This may reactivate the “genome guardian” function of p53 and is therefore an interesting approach for treating various oncological indications.
Under the terms of the collaboration and license agreement, Boehringer Ingelheim will lead development and commercialisation of the potential mdm2/p53 inhibitor products to capitalise on its global marketing and sales expertise. Boehringer Ingelheim will pay significant up-front and near-term payments to Priaxon including research funding to support further discovery efforts. In addition, Priaxon will be eligible to receive from Boehringer Ingelheim EUR 86 million in milestone payments upon achievement of certain development, regulatory and commercial milestones as well as royalties on potential future net sales of products.
The companies will work jointly to identify and advance candidates into pre-clinical development. Thereafter, Boehringer Ingelheim will drive the development and commercialisation of the potential cancer treatments arising from the collaboration.
"We are delighted to work with Priaxon on novel targeted cancer therapies, to further broaden our Oncology Pipeline. The discovery of p53 and its protein-protein interactions in a broad range of human cancers has been a milestone in cancer biology, yet finding potent inhibitors of these interactions has been challenging. With our partners, we see a significant potential for this treatment modality in patients with locally advanced or metastatic cancers for whom available treatment options are not satisfactory," said Dr Wolfgang Rettig, Corporate Senior Vice President Research at Boehringer Ingelheim.
“Using the strength of its unique drug discovery platforms, Priaxon was able to develop new promising mdm2/p53 inhibitors with high potency”, said Dr Juergen Kolb, CEO of Priaxon. “Our collaboration with Boehringer Ingelheim and its experts in oncology provides the resources and the capabilities to drive this programme forward. Both Boehringer Ingelheim and Priaxon are looking forward to working together with the goal to develop a small molecule inhibitor for this protein-protein interaction of high potential.”
About mdm2/p53 Inhibition
The human p53 tumor suppressor protein has been one of the most investigated proteins in cancer research due to the fact that loss of p53 function through mutation and/or deregulation is involved in about 50% of all human cancers. The role of p53 in controlling the cell cycle and monitoring the integrity of the genome has made it known as the “guardian of the genome”. Besides the functional loss of p53 through mutation, it can also be inactivated by the overexpression or amplification of MDM2 (murine double minute 2), which is the case in many p53 wild-type tumors. Thus, disruption of the MDM2–p53 interaction is considered a novel therapeutic strategy for cancer cells that still are endowed with wild-type p53, and a variety of small molecule drug like compounds have been reported that bind to the p53 binding site of MDM2.
Priaxon is an emerging pharmaceutical company building a pipeline of novel drug candidates in different therapeutic fields, but mainly focusing on protein-protein interactions in oncology and other diseases. The goal is to discover and develop candidates for validated but hard-to-drug targets using two orthogonal drug discovery platforms.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
1 mdm2 is is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene.