The five drug candidates are the first molecules into the pipeline of newly formed Synosis Therapeutics, which plans to specialise in using 'smart' clinical trials to develop treatments for CNS disorders such as Alzheimer's, Parkinson's, drug dependency and pain.
Dr Ian Massey, CEO of Synosis, explained to DrugResearcher.com that Synosis hopes to have a real impact on improving patient quality of life and that these five compounds were only the beginning.
"Traditionally, CNS has been a difficult area to work on. The challenges depend on the indication but it is often difficult to determine how much drug is getting into the CNS and which part of the CNS it is getting to," said Dr Massey.
He explained that this can lead to the somewhat marginal efficacy and significant side effects seen with some current therapies.
Dr Massey plans to overcome these hurdles by using small clinical trials to rapidly establish proof-of-concept leading to a better understanding of both a drug's action and any side effects, earlier in development.
Synosis has refocused diagnostic imaging techniques, such as EEG or PET scans, to use during the clinical trials to show how the drug influences brain activity, whether in a normal state, during cognitive tasks or in a disease state and also determine the concentration of molecules in specific regions of the brain.
For example, one of the molecules, SYN-117 inhibits dopamine beta-hydroxylase, the protein responsible for converting dopamine to norepinephrine. Increased dopamine levels are associated with the reversal of motor defecits in Parkinson's disease and modulating this neurotransmitter can remove the reward response associated with addictive drugs.
Dr Massey explained that the research team can track where SYN-117 is present in the brain and in what concentration and also the concentration of dopamine levels. Overall, this indicates how effective the drug is - establishing a suitable dose - and where it acts, indicating potential side effects.
The technology can also indicate other potential uses for a candidate molecule, possibly opening the drug up as a viable treatment for another disorder.
The data can then be used to decide which molecules should progress into larger clinical studies and to design studies that are more effective and more likely to prove successful.
Synosis wants to acquire more of these compounds, neglected by large pharma often for business rather than scientific reasons. Dr Massey said: "We want to assemble a portfolio of molecules, not all of which we would be expected to become drugs, and conduct small studies to select and prioritise compounds among that portfolio to go onto later stage, Phase IIb and III trials."
By doing this, the fledgling company hopes to avoid the trap fallen into by many other pharma start-ups where they rely too heavily on just one or two compounds, only to see them fail and their share price plummet.
"Having a portfolio is very important. If you only have one or two compounds, there is no real incentive to make rigorous selections," said Dr Massey.
"The goal is to identify molecules that already have clinical data associated with them that we can immediately utilise in CNS indications."
Four of the compounds are in Phase I trials and Roche had also conducted Phase II trials on one of those, albeit for a different disorder to the one currently being studied.
Under the terms of the deal, the clinical development of all five drug candidates will fall to Synosis with Roche retaining a call-back option on one and a right of first negotiation on another. The rights to the remaining three programmes belong entirely to Synosis and the company can choose whether to market any products alone or with a partner.
Although the financial terms of the deal were not disclosed, Dr Massey revealed that the potential market for any of the five molecules could be in the range of $500m to $1bn (€383m to €769m).
Dr Massey doesn't believe that the fact that Roche had discontinued development of these particular compounds should be seen to indicate there is something wrong with them. And he should know: until recently he was head of research and preclinical development at the Roche campus in Palo Alto, California, US.
He said: "There are many diamonds in the rough sitting on the shelves of pharmaceutical companies."
He added: "I believe Roche sees [Synosis] as a trusted pair of hands and have shown confidence in us to be able to create value from these molecules."