Mirati Accelerates Drug Discovery With OpenEye Platform Powered by AWS and Intel

Mirati Therapeutics uses AWS and Intel to screen several billion molecules in under 24 hours, accelerate the drug discovery process, and more rapidly discover molecules that can be turned into lifesaving oncology therapeutics. Mirati is a clinical-stage biotechnology company that advances breakthrough therapies for cancer patients. The company uses OpenEye Scientific’s Orion, an AWS- and Intel-powered molecular design platform that runs on Amazon EC2 instances.

Mirati Therapeutics, Inc., is a clinical-stage biotechnology company with a noble mission: discovering, designing, and delivering breakthrough therapies that transform the lives of patients with cancer and their loved ones. Among the drugs in the company’s developmental pipeline of novel therapeutics are KRAS inhibitors, which are targeted therapies that stop tumor growth caused by a mutant version of the protein KRAS.

Mirati faces several key challenges when it comes to molecular design and drug discovery. Like all pharmaceutical and life sciences companies, Mirati must accelerate the discovery of new drugs to get them to market rapidly. “Getting a compound into the clinic is a complex and challenging endeavor,” says David Lawson, senior director of structural chemistry at Mirati Therapeutics. “Going from absolute zero as a starting point and then finding and crafting initial hits into a compound that is tolerable and efficacious is never an easy task.”

Mirati sought an easier, more scalable, and cost-effective technology to enable virtual screening of compounds. Virtual screening is a way of computationally evaluating the likelihood that a compound will bind and inhibit a target protein. “We wanted to build a scientific computing infrastructure from the ground up with a minimal in-house footprint,” Lawson says. “To do that, we wanted to leverage the cloud for its on-demand scalability.”

Mirati’s search for a better technology platform led it to AWS Partner OpenEye, Cadence Molecular Sciences, a life sciences division of Cadence Design Systems that specializes in computer-aided drug design. OpenEye’s Orion molecular design platform runs on Amazon Web Services (AWS), which provides researchers with scalability and access to hundreds of thousands of processors.

Orion runs on Amazon Elastic Compute Cloud (Amazon EC2) C4, C5, C6i, R5, and M5 instances, all powered by Intel Xeon scalable processors. “OpenEye has decades of experience compiling, running, and optimizing our software on Intel processors, both on our own computers in our data center and at our customer sites,” says Jharrod LaFon, executive vice president, OpenEye Cadence Molecular Sciences.

“We had a lot of confidence that our algorithms would behave correctly and similarly in the cloud as they do on our own hardware. As newer Intel chips become available on AWS, we tend to take advantage of those very early on. One example is the C6i that recently came out. We've already ported our code to use those, and in some cases we've seen up to a 15 percent speed increase. We're very happy with that result.”

Using Orion, Mirati computational chemists can create, model, calculate, visualize, and analyze chemical compounds through virtual screening and OpenEye’s Gigadock™ functionality, which performs massively parallel molecular docking using tens of thousands of cores on AWS. “We use Orion to look for new chemical material, using the virtual screening process to investigate virtual libraries that can be rapidly synthesized,” says Lawson. “These initial hits are novel starting points that can then be evolved into potent, efficacious, tolerable drugs for treating cancer.”

Using the Orion platform, Mirati has much more scalability than it had with its previous desktop applications. “Right now, using Orion on AWS with Intel technologies, I can screen several billion molecules in less than 24 hours,” says Lawson. “That is completely out of the realm of what I can do on my own laptop or workstation. For a relatively small amount of money, we can identify, synthesize, and test hundreds of compounds. And every time that we've done it, we have found at least one or two compounds, if not more, that register in our assays.”

Mirati also only pays for cloud resources as needed. “With Orion on AWS, we have access to a vast amount of compute power on demand without having to maintain our own server room and hardware. We’re not paying for full-time resources when we have a part-time need,” Lawson says.

Mirati has eased its research processes by relying on Orion, which provides an integrated solution including both code and infrastructure to enable drug discovery. “Mirati can go from zero to an entire virtual data center tailored toward early-stage drug discovery, performing virtual screening, with a single click,” says LaFon. “Researchers don't have to install any software on their desktop, and they have access to vast amounts of compute and storage resources.”

As a result, Mirati does not have to maintain its own high-performance computing clusters. “It frees up resources for us,” Lawson says. “I don’t need to look after the hardware and infrastructure, and we can focus on what we're good at: the science, the computational chemistry, and the medicinal chemistry of designing these drugs.”

With the OpenEye solution, Mirati has accelerated the drug discovery process. Now the company’s researchers can more quickly identify molecules that may impact targets like KRAS and provide meaningful breakthroughs for patients with hard-to-treat cancers. “Using OpenEye’s Orion, we’re able to come up with lists of make-on-demand compounds that we can purchase and have in our hands and into the testing process within a few weeks,” says Lawson. “Further down the line, as we're evolving these initial hit molecules into leads, we’re able to evaluate what we call synthesis-focused libraries. We take a hit molecule and then algorithmically add on available building blocks to create virtual molecules that are amenable to rapid synthesis in the lab by our chemists. Orion helps us evaluate which of the hundreds of thousands of virtual molecules in these libraries we should invest in synthesizing.”

By relying on OpenEye’s Orion to power its research, Mirati can stay focused on its mission of delivering medicine to cancer patients. “The end product of what we do is in our minds every day,” says Lawson. “We want to do everything we can to accelerate that process, and that’s what OpenEye, AWS, and Intel are enabling us to do.”