All of the compounds in the collaboration target specific neuronal nicotinic receptors (NNRs) across a range of therapeutic areas, including pain, smoking cessation, obesity, addiction, and Parkinson's disease. The most advanced compound is TC-2696, which is currently in Phase II trials for acute post-operative pain.
GSK will make an initial payment of $35m to Targacept with the remainder of the cash contingent on Targacept achieving specified discovery, development, regulatory and commercial milestones across the five therapeutic areas mentioned. The US company will also receive tiered double-digit royalties dependent on sales achieved.
As part of the deal, Targacept has retained an option to co-promote TC-2696 in the US and also another neuropathic pain compound - the preclinical candidate called TC-6499.
Neuronal nicotinic receptors are neurotransmitter-gated ion channel receptors that play a central role in modulating synaptic neurotransmission, fundamental intracellular signalling pathways, neuronal viability and synaptic architecture and function. There are several receptor subtypes with different functions, which is why the collaboration covers a range of therapeutic applications.
"The breadth of this alliance validates the importance of NNRs in the potential treatment of a broad range of CNS-related disorders and diseases," said Dr Donald deBethizy, CEO of Targacept.
For each subtype, Targacept will use its 'Pentad' technology to develop candidate drugs, which will then be tested in a Phase II 'proof-of-concept' trial. Once that's done, GSK will fund all future development and commercialisation costs.
To help Targacept scientists do this, the company has developed Pentad - its in-house drug discovery software. As well as being able to predict the interaction between drug and target, the software also generates pharmacokinetic profiles, which the company claims can predict the likelihood a given molecule will succeed in subsequent preclinical and clinical research.
Unusually for computational drug discovery, Pentad uses quantum mechanics instead of classical descriptors to predict the behaviour of molecules over time. The software also includes algorithms to predict a compound's properties and programmes that can be used to design new compounds similar to others that are found to be effective at targeting a specific NNR. These data are then combined with biological data compiled from an in-house compound library.
The deal is the second large deal this month. Earlier in July, Merck & Co. announced a deal potentially worth over £1.1bn (€805m) with Ariad. However, this deal centres on just one drug: AP23573, Ariad's novel inhibitor of mammalian target of rapamycin (mTOR). This protein is a popular anticancer target as it plays a key role in regulating cell proliferation, cell growth and cell survival.
AP23573 is expected to begin Phase III trials as a treatment for metastatic sarcomas in the next few months. The first and currently only marketed drug that targets this therapy is Wyeth's Torisel (temsirolimus). The drug was recently approved by the US Food and Drug Administration (FDA) to treat advanced renal cell carcinoma (RCC).
