The power of three

SOUTH PLAINFIELD, N.J.—In late November, Roche and PTCTherapeutics joined forces to tackle spinal muscular atrophy (SMA), a geneticneuromuscular disorder that causes muscle weakness. SMA affects one out ofevery 10,000 children, but currently has no effective treatment.

In the hopes of filling this high-unmet medical need, Rochehas licensed PTC's SMA program. The agreement gives PTC $30 million upfront, upto $460 million in development and commercial milestone payments anddouble-digit royalties on commercial sales. Development will be overseen by ajoint steering committee.

At its core, the partnership is "really about developingfirst-in-class treatments for a disease with a high, unmet medical need," saysDr. Stuart Peltz, president and CEO of PTC. SMA is caused by a missing ordefective SMN1 gene, which results in reduced levels of the survival motorneuron (SMN) protein.

Because the disease affects the muscles that controlbreathing, SMA can cause premature death. Life expectancy tends to vary by SMAtype, which is generally associated with age of onset of symptoms. The severityof symptoms varies widely depending on SMA type involved and the stage of thedisease, but even its moderate form, SMA can limit function and mobility.People with SMA either never acquire, or progressively lose, the ability towalk, stand, sit and eventually move. People with SMA often develop bone and/orspinal deformities that may require surgical treatment. Respiratory illnessesmay be more common for people living with SMA and can be severe.

There is no known cure for the disease, which could beeligible for orphan status by regulatory authorities. Should that status begranted, this could reduce the time needed for a drug to reach patients.

The compounds in PTC's SMA program treat the underlyingcause of the disorder. Early testing in research models of the disease hasshown that the compounds increase SMN levels in the central nervous system,muscles and other tissues. The program includes three compounds currently inpreclinical development, as well as several potential back-up compounds.

"Not only do we have one compound to move forward, but wealso have backups, so if for any reason the compounds fail, we have others wecan move forward," notes Peltz.

The basic science of PTC's approach to drug discovery "isvery attractive," says Santarelli, adding that it "unlocks the possibility ofimpacting therapeutic targets that would not be possible with standardapproaches."

The partnership is Roche's first experience working in thearea of SMA, says Luca Santarelli, global head of Roche Neuroscience, and headds that the agreement will boost Roche's work in the area of central nervoussystem diseases.

"It is our goal to get very close to the science and developmechanistic agents, allowing us to individualize medicine for every patient.This makes us different from a lot of others that have played in this field inthe past, and we believe this goal is part of the reason we are still in thisgame," Santarelli says.

Roche was compelled by "the serious nature of thiscondition, its very high unmet need and the fact that it affects children,"adds Santarelli. "For me, this was a very strong motivator to identify apotential treatment. In this case, the ability to achieve normal-levelexpression of a protein lacking because of a genetic deficit is the key tosolving this disease."

Notably, PTC and Roche consider their work a "three-waypartnership," as the SMA Foundation is also closely involved. Founded in 2003,the nonprofit organization has to date invested more than $100 million ondeveloping a portfolio of drug discovery assets to treat SMA. PTC's program hasbeen developed in partnership with the SMA Foundation, which will remain activein the collaboration.

"It's quite unique that an advocacy group places patients asequal members of this kind of collaboration," says Peltz.

The foundation's involvement in the partnership "adds a lotof value" in that it is scientifically sophisticated, not just dedicated toproviding funding or other resources for patients.

"Unlike other charitable foundations, this one decided to goafter the science," Santarelli says. "Their mission is solving the disease andgetting to its root problem. In addition to that, what they bring to the tableis a connection with the families, caregivers and doctors. This gives usinstant access to a network of patients with whom we conduct trials and get atargeted, sophisticated understanding of the disease."

"At the end of the day, these organizations are not onlyyour customers, but people who will help or hurt you in moving forward," Peltzadds. "If they are not yelling for it, there is probably not someone working onit. They are not only doing something scientifically exciting, but theirmission is so important. If this works, we will have changed the lives of thesepeople."

Roche and Labcyteintegrate systems to boost qPCR-based RNA/DNA analyses

SUNNYVALE, Calif.—Roche and Labcyte Inc. will cooperatearound high-speed, miniaturized quantitative PCR (qPCR) to monitor theexpression of tens to thousands of genes for therapeutic research, Rocheannounced last month.

Roche's RealTime ready Cell Lysis kit enables gene expressiondirectly from cell lysates. Coupled with Echo liquid handlers and newlyreleased tissue culture microplates from Labcyte, researchers can greatlysimplify high-throughput qPCR analyses, Roche said in a press releaseannouncing the integration.

According to Roche, this process can be fully automatedusing the Access Workstation from Labcyte, which integrates the Echo liquidhandler with either the LightCycler 480 or LightCycler 1536 Instrument. Geneexpression profiles derived in a one-step process directly from cells can nowbe streamlined into a simple automated workflow, significantly increasingproductivity, said Roche.

"This integrated platform reduces data costs associated withgene expression profiling, allowing efficient incorporation of qPCR into theearly stages of drug discovery," said Dr. Matthias Hinzpeter, Roche's qPCR/NAPsystems project leader.