Teva gets in on protein kinase B act

By Mike Nagle

- Last updated on GMT

Related tags: Pharmacology, Chemotherapy

Teva Pharmaceuticals has licensed some protein kinase B technology,
including preclinical drug candidates, adding to the buzz around
this up-and-coming cancer target.

The deal is an all-Israeli affair with Teva buying the goods off the Israeli arm of DeveloGen. All of the drug candidates involved target protein kinase B (PKB), sometimes also called Akt, and validates this targets increasing popularity with anticancer drug developers. PKB is a serine-threonine kinase that can be activated in many different ways. It has been implicated both in a tumour cell's ability to avoid cell suicide (apoptosis) and also in its ability to divide and grow rapidly. The target has also been found to promote resistance to chemotherapy. One of the reasons it is such a popular target is that it works on the same pathways as other cancer drugs but earlier on. This upstream effect can then block more than one alternative cancer target, including phosphoinosotide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR). Several other companies are developing drugs aimed at PKB. Keryx Biopharmaceuticals recently presented the results from Phase I and II trials for its own small molecule therapy perifosine (KRX-0401). Developed in conjunction with AEterna Zentaris, the alkylphospholipid inhibits the activation of PKB by preventing it from having phosphate groups added to it. In January, Exelixis submitted an investigational new drug application (IND) to the US Food and Drug Administration (FDA) for XL418. This drug is slightly different in that it blocks both PKB and S6 Kinase (S6K). The company believe this is the first dual inhibitor of these targets to enter clinical development. Scientists at ProXara Biotechnology, a spin-out from the University of Bristol, UK, are also developing PKB inhibitors. Recently, the service division of pharma company Galapagos, called BioFocus DPI, were brought in to provide lead optimisation services for the university's programme. The €2m deal was possible at least partly due to the university recently receiving a €4.3m research grant from the Wellcome Trust's Seeding Drug Discovery Initiative to take this research programme forward. A more advanced research project can be found at Rexahn Pharmaceuticals. It has developed Archexin, an antisense string of 20 nucleotides that is complementary to the messenger RNA used to translate the PKB gene into its protein product. The company recently received regulatory clearance to begin Phase II clinical trials. Abbott Laboratories has also been examining this cancer target. One of its drugs in the PKB programme is A-443654, and the company has been using primary cells to examine which proteins, in addition to the PKB target, are affected by it. Astex is also in on the game, in a collaboration with AstraZeneca. Astex described PKB as "one of the most exciting new targets in the class of molecularly-targeted anti-cancer agents"​. This research programme is further back than the others, with the companies hoping to chose a candidate for preclinical testing sometime this year. The exclusive global license for Teva was arranged through DeveloGen's new subsidiary, called CureGenics Limited. Although details were not divulged, DeveloGen will receive milestone payments and royalties from any commercialisation. "With Teva, we have found a strong partner for this highly innovative program,"​ said Carsten Dehning, chief financial officer of DeveloGen. "Teva's proven expertise in the successful development and marketing of ethical drugs will be instrumental in bringing this novel treatment to the many patients suffering from cancer."​ Dehning went on to say that the reason the PKB programme was available was as part of DeveloGen's plans to focus on metabolic and endocrine disorders.

Related topics: Preclinical Research

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