DUBLIN – Shares in Prothena Corp. plc should get a pre-Christmas boost when Nasdaq opens on Thursday morning to news of a drug development deal in Parkinson’s disease with Roche Holding AG worth up to $600 million in up-front and milestone payments.

That headline figure includes $45 million, which comprises an up-front payment and a near-term milestone, payable when Prothena’s lead drug, an anti-alpha-synuclein antibody PRX002, enters the clinic.

“A majority of the $45 million is in the up-front payment,” Tran Nguyen, chief financial officer of Dublin-based Prothena, told investors on a conference call late on Wednesday. The rest of it should arrive during the first half of next year, when PRX002 is due to begin a Phase I trial.

The milestones are also split into two components: $380 million is payable on the progress of PRX002 through development, regulatory approval and first U.S. sales; the remaining $175 million is tied to ex-US sales targets. Prothena would also receive sales royalties, up to a double-digit percentage, on ex-U.S. sales.

Prothena will receive a 30 percent share of profits on U.S. sales and will shoulder 30 percent of the development costs. It also has an option to co-promote the drug, which it can exercise once a BLA has been filed. That would enable the company to establish a specialty commercial infrastructure, although that decision is down the pike.

As part of the alliance, the two companies are also entering a Roche-funded research collaboration, the agenda of which includes the development of diagnostic biomarkers to support the drug development effort and the use of Roche’s brain shuttle technology, which is designed to boost the delivery of biologic drugs to the brain. It is based on the addition to antibodies – and potentially other therapeutic molecules – of targeting agents that bind protein receptors on the surface of the blood-brain barrier.

The alliance may extend to other synucleinopathies, such as dementia with Lewy bodies, multiple system atrophy and neurodegeneration with brain iron accumulation, all of which are characterized by the inappropriate aggregation of alpha-synuclein protein within neurons and glial cells.

For now, though, the main focus is on Parkinson’s. “It’s thought to be the real smoking gun in Parkinson’s disease,” Prothena CEO Dale Schenk told BioWorld Today. Alpha-synuclein is normally found in presynaptic nerve terminals of neurons and is thought to play a role in coating synaptic vesicles, which store neurotransmitters prior to their release.

The disease process is, Schenk said, thought to be linked to the inappropriate distribution of alpha-synuclein between neurons. The absolute level of alpha-synuclein may not be that different in Parkinson’s patients, as compared with healthy patients, but it seems to be distributed in the wrong places. PRX002 is designed to block that process, rather than interfere with the protein residing within the neuron. “The protein may not even get to that form of it,” he said.

Animal studies provide some level of comfort on the safety front. Knockout mice “do ok,” he said, although there are subtle differences between them and wild-type animals.

Prothena was spun out of Dublin-based Elan Corp. plc last December in order to continue development on early stage, high-risk antibody development programs focused on neurodegenerative diseases. Its name offers a nod to its heritage in Athena Neurosciences, the South San Francisco firm Elan acquired almost two decades ago, which gave rise to its multiple sclerosis drug Tysabri (natalizumab) and to its high-profile but ultimately unsuccessful Alzheimer’s disease program.

Elan’s Alzheimer’s program exemplified the difficulty of halting or slowing a disease process that only becomes apparent in patients once it had been under way for a considerable period of time. PRX002 is also intended as a disease-modifying drug but, according to Schenk, the parallels end there.

“Alzheimer’s is a central [nervous system] only disease – there’s nothing peripheral about it,” he said. In contrast, some of the early symptoms of Parkinson’s involve the gastrointestinal tract and fluctuations in heart rate. Moreover, alpha-synuclein is also found, at low levels, in most tissue types, apart from the liver.

The deal, coupled with a share offering in October that netted $85 million, significantly extends Prothena’s cash runway well beyond 2014. The company reported $101.9 million cash on Sep. 30. The deal also provides some early upside for investors in Perrigo Co., of Allegan, Mich., which will hold an 18 percent stake in Prothena once its $8.6 billion cash-and-shares acquisition of Elan is completed.