Reducing the Cost and Increasing the Precision of Future Medicines

DURHAM, NC, UNITED STATES - Feb 10, 2015 - While the merits of the proposed Precision Medicine Initiative are hotly debated, Cloud Pharmaceuticals, a drug development start-up in Durham, North Carolina, has been quietly making the promise of precision medicine more attainable.

Cloud Pharmaceuticals is breaking new ground in the field of in silico drug discovery - that is, performed on a computer or via computer modeling and simulation of molecules.

The successful treatment of diseases depends on effective medicine, consisting of molecules that bind to specific biological targets, says Shahar Keinan, CSO of Cloud Pharmaceuticals. Our technology, called Inverse Design, computationally designs small molecules and peptides that inhibit the activity of protein targets, which are produced by the genes responsible for certain pathologies.

This design process takes place much more quickly and effectively than traditional methods. Qualified drug candidates can therefore be identified and advanced to the next stages of development more rapidly to reduce the cost, increase efficacy, reduce toxicity, and enable precision medicine by providing more than one drug per target.

Overcoming the obstacles of in silico

How can Cloud Pharmaceuticals novel technology deliver on the promise of faster, more effective drug design? Past in silico methods, such as docking, have inconsistent results due to inaccurate prediction of activity. Inverse Design overcomes these challenges by combining three different technologies, as Cloud Pharmaceuticals CEO Ed Addison explains.

There are an estimated 10^65 stable molecules with a molecular weight below 850 available for exploration. Researching this space by direct enumeration and evaluation is too slow and too expensive. We use patented search algorithms to locate the best molecules in that vast space, Addison says. Our method combines high-performance cloud computing, quantum mechanics/molecular mechanics (QM/MM), and molecular property simulation. This approach enables us to calculate accurate binding affinities in a fraction of the time and choose only molecules that could make a useful drug. Plus were able to identify novel drug candidates that exhibit low probability of toxic side effects and high probability of success.

Targeting proteins at a molecular level

The efficiency and speed of developing novel drug candidates with Inverse Design is that it enables the creation of a virtual hit list of molecules that bind to protein targets. More than one drug can be developed per indication that can later be matched to people with certain genetic markers. This targeting enables adaptive drug trials so the best drugs can be chosen for a given patient, changing the drug development paradigm to be more suited to precision medicine.

Very often, the same protein will mutate and cause different types of illness or disease, Keinan adds. Therefore, targeting proteins at a molecular level helps to identify more effective treatment protocols.

Bringing precision medicine within reach

Its clear that the worldwide pharmaceutical industry is in need of new treatment options that target smaller market segments, are developed faster, and have novel IP, greater drug safety, efficacy, and affordability. Cloud Pharmaceuticals is poised to help.

If the vision of precision medicine and eventually personalized medicine is to happen, it is important that new breakthroughs and better applications emerge for computational drug discovery, Addison says. Accurately calculating binding affinities between a protein and a small molecule is critical to rationally designing new drugs - and thats exactly what we do.