Going small for broad potential

CAMBRIDGE, Mass.—Nimbus Discovery LLC, a biotechnologycompany discovering novel medicines against what it calls "exciting butpreviously inaccessible disease targets," announced May 8 a co-developmentagreement with Shire PLC focused on small-molecule treatments for several raregenetic diseases known as lysosomal storage disorders (LSDs).

Through the collaboration, the companies plan to use Nimbus'computational chemistry approach to discover and develop novel,disease-altering therapies for LSDs, many of which remain untreated because ofchallenges in creating drugs that can effectively reach the disease site.

"The significant potential of this partnership is thedevelopment of the first small-molecule agents designed to penetrateinaccessible tissues while offering the convenience of an orally administeredpill," the companies say.

"Our target is one that has never been drugged before andhas proved to be quite challenging with regard to traditional approaches,"Jonathan Montagu, Nimbus' vice president of business development andoperations, tells DDNEWS. "So, this isideal for us. It's a joint target that bring all the weight of our breakthroughcomputational approach to bear, while Shire brought us its skills aroundbiological understanding, commercial potential and patents."

Enzymes often have limitations in terms of treatmentpotential, he notes, while small molecules can get to places where enzymes aretoo large to go.

"And in the case of enzyme replacement approaches," hecontinues, "you tend to end up with one drug for one disease. In the case of asmall-molecule approach like we're pioneering with Shire, one molecule couldpotentially treat multiple diseases, giving much better market potential."

The Nimbus-Shire collaboration, the companies say, is theresult of a joint assessment of a series of important rare disease targets withsignificant unmet medical need. One target was ultimately chosen to be theresearch focus, as a sort of "test drive" of Nimbus' methods, and thecollaborative relationship could extend beyond it later. Under the terms of theagreement, Nimbus will use its research and development platform to extensivelyprofile molecules against the agreed-upon disease target and will deliver adrug candidate that is ready to enter late preclinical studies.

Up to the point the collaboration achieves an actual drugcandidate, Nimbus will control and conduct all research related to the effort,and then Shire will have an exclusive option to acquire the program. Shirewould then be responsible for all clinical development and futurecommercialization activities. Nimbus would be eligible to receive preclinical,development and commercial-stage milestones.

As is Nimbus' style, the program will be set up as its owndedicated subsidiary under an LLC umbrella, so that its intellectual propertyand assets can be more easily acquired, such if Shire takes over the program,Montagu says. Also, as Nimbus notes on its website, this structure "solves theclassic drug discovery illiquidity problem where it takes seven to 10 years toget a return on capital via M&A or an IPO. The LLC structure enablesshareholders to cycle capital back to investors in a tax-efficient manner on aper-project basis."

"This collaboration validates our computationally driven,structure-based drug discovery engine and innovative partnering model," saidDr. Rosana Kapeller, chief scientific officer of Nimbus, in the news releaseabout the deal, adding that this is Nimbus' first alliance with Shire, "acompany that shares our passion for uncovering breakthroughs in highlysought-after disease targets that have proven inaccessible to traditionalindustry approaches."

It is also worth noting that this is the first dealannounced through Shire's strategic alliance with Atlas Venture, whichidentifies investments for early-stage venture creation around rare geneticdiseases. That multiyear collaboration deal was announced in December 2011. Thepartnership leverages Shire's capabilities and knowledge in the research anddevelopment of rare diseases with Atlas' expertise in the formation and growthof early-stage companies.

"As a leader in rare diseases, this partnership is anotherway for Shire to ensure that we expand into new disease areas and continue toapply cutting-edge technologies in this space," said Philip J. Vickers, Shire'ssenior vice president of research and development, when the collaboration wasannounced in 2011. "Working with an organization like Atlas provides us with anew source of external expertise that is complementary to our internalcapabilities and has a clear focus on Shire's goal of bringing innovativetherapies to patients suffering from rare diseases worldwide."

The alliance structure was designed to provide anopportunity early in the venture process to utilize all of Shire's capabilitiesin rare diseases from research to commercialization, while leveraging theextensive Atlas network and experience in company formation.

"The partnership with Shire is truly synergistic and leveragesour individual strengths to create and fund new startups around high potentialmedical science early in the R&D cycle," said Dr. Bruce Booth, an AtlasVenture partner.

Looking to the more recent deal that brought Nimbus into themix, Vickers says, "Nimbus is groundbreaking in their approach to drugdiscovery and, in a short period of time, have already assembled an impressivetrack record in delivering clinical candidates for challenging diseasetargets."