My visit to Nimbus, Bill Gates' bet on virtual drug discovery

The nerve center of Nimbus Discovery, a largely virtual biotech start-up, resides in the offices of Atlas Venture in Cambridge, MA. Bruce Booth, an Atlas partner and chairman of the small company, recently talked to me at the firm's offices about how Nimbus is making use of computer-aided drug discovery software from Schrödinger to advance a pipeline of potential treatments for cancer, obesity and other conditions.

Microsoft ($MSFT) chairman Bill Gates was announced as one of Nimbus' seed investors in March, raising the profile of the young firm and shedding light on its unique relationship with Schrödinger, in which Gates invested last year through his Cascade Investment group. Nimbus hasn't disclosed how much it has brought from Gates, Atlas and its other seed investors, yet more details could be in the offing; the company is planning a Series A round of funding in the near future.

Schrödinger, a global provider of chemistry simulation software for pharmaceutical companies, is a major shareholder in Nimbus. Ramy Farid, Schrödinger's president, co-founded Nimbus with Atlas' Booth in 2009 and sits on its board, the chairman says. The start-up has special access to Schrödinger's software, support from the 21-year-old company's computational chemistry experts and business expertise from Atlas.

While it's too early to say with Nimbus' drugs will succeed in clinical trials, the upstart has been able to show how the use of new software for understanding disease proteins and other tools have helped speed its drug discovery efforts, according to Booth. The firm also relies heavily on a global network of contract research organizations for work related to its drug discovery efforts. Its virtual organization also uses Schrödinger's cloud computing assets for some of its computer-based experiments. Its virtual drug discovery model might seem highly suspect to traditional Big Pharma R&D folks, but pioneering different ways of doing business is a source of pride for Booth and Nimbus.

"True virtual drug discovery is still very much at the forefront of thinking, and there are a lot of skeptics who don't believe that virtual drug discovery will work, especially among the old guard at big pharmaceutical companies," Booth says.

One of the key software tools for Nimbus' early discovery work has been Schrödinger's WaterMap system, which is designed to help researchers understand the location and energetics of water molecules at specific sites on disease-related proteins. The software might provide Nimbus with an edge, especially in cases where there are undiscovered aspects of water molecules at certain protein drug targets. For example, Nimbus' lead program is focused on interleukin-1 receptor-associated kinase-4, or IRAK4, which is a promising target for certain inflammatory and oncology cases yet is difficult to drug in part because of its shallow pocket where compounds can bind in order to inhibit its activity.

A Nature paper in December indicated that IRAK4 might play a major role in keeping cancer cells alive in certain patients with a form of large B-cell lymphoma. Aided by insights about the water molecules at the protein, Nimbus has moved swiftly, starting its initial wet lab work in August 2010 at a CRO to gaining efficacy data from animal experiments with its potential IRAK4 inhibitors in recent months, according to Booth. The firm is making similar progress with its other programs involving targets such as acetyl CoA carboxylase (ACC), which is an enzyme implicated in burning and storing fats, according to the company.

"I think the fact that this company went from its first wet chemistry work in August and we already have oral in vivo data in eight months is incredibly impressive," Booth says. The relationship with Schrodinger has been "a core part of it, as has been incredibly important partners to us" such as our chemistry CROs in China.

Indeed, computer-based drug discovery isn't perfect and Nimbus has to confirm what its software indicates about drug targets and design at actual bricks-and-mortar labs, Booth says. So after computational chemists from Schrödinger design molecules, those molecules are synthesized for real and then tested in labs to show whether they have an intended effect. Then data from the wet lab experiments can be fed into the computer models. "Like all drug discovery, there's an iterative process around design, synthesis, testing and insight," Booth says.

To be clear, Nimbus doesn't have the market on computer-based drug discovery cornered. Yet it'd be tough to duplicate the start-up's capabilities from scratch because it is able to tap the technology and expertise that Schrödinger has spent more than $125 million to build over the years. (In these fiscally conservative times for venture-backed biotech, it seems unlikely for an upstart to raise enough cash to try to build such capabilities on its own.) Locus Pharmaceuticals has raised big chunks of capital from investors to build up computer-based drug design capabilities, yet the 12-year-old firm hasn't been able to deliver a new drug to the market yet.

Nimbus might be able to move quickly and efficiently with its virtual business model and unique access to Schrödinger's technology and people. If it's approach to drug discovery yields some clinically validated candidates at some point in the next several years, Atlas, Schrödinger and Gates might see their gamble on the firm's business strategy pay off. - Ryan McBride (twitter | e-mail)

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