Building a Practice of Predictive Medicine

One goal of modern, personalized medicine is to find signs of diseases early enough to treat them before they rage out of control.

Integrated Diagnostics Inc. (Indi)—which was formed using in-licensed patents and patent applications from both Caltech and the Institute for Systems Biology (ISB)—is working to identify diseases at their earliest stages, before a patient has symptoms or realizes there is an illness. Indi is changing the practice of medicine from a reactive one in which diseases are treated only when they are full-blown, to a predictive one that allows for successful early treatment.

Indi's cofounders are Leroy Hood, a Caltech alum (BS '60, PhD '68) and former professor and chair of biology, who pioneered development of the automated DNA sequencer; James Heath, the Elizabeth W. Gilloon Professor and professor of chemistry and director of the National Cancer Institute–funded NanoSystems Biology Cancer Center; Paul Kearney, who serves as president and chief scientific officer; and David Galas, one of Hood's former collaborators at ISB. The company designs new diagnostic tests that can identify blood-based proteins that provide early warning of lung cancer, Alzheimer's, and other diseases.

"Proteins are the most information-rich of biomolecules," Heath says. "Disease diagnostics has always been done at the protein level, but protein measurements haven't changed in the past 30 years." Getting diagnostic information on one protein, such as a measure of its level in the blood, costs $50 to $100, Heath says, and when trying to diagnose cancer, for example, investigators are searching for panels of proteins—perhaps dozens of modified proteins that, together, can report on, for example, the benign or malignant status of a tumor. Detecting such a large number of proteins, and interpreting how those proteins reflect the patient's disease condition, is challenging. Heath and Hood have developed techniques for simplifying the process.

Hood and Kearney's contribution involved developing an application of mass spectrometry called focused proteomics, which investigators utilize to study protein structure, function, changes, and interactions to determine their role in human health. The method identifies the presence of certain proteins based on measuring the masses of several pieces of those proteins, which can serve as a fingerprint. "Ten years ago, the use of mass spectrometry to measure protein abundance was extremely limited, and results from one laboratory were often not reproduced in other labs," Heath says. "Indi developed tools that overcame this limitation and allowed the levels of several hundred proteins to be quickly and accurately measured from a single patient sample. Those tools open up the blood as a powerful window into disease and health diagnostics."

Heath invented two technologies that have improved the measurement of blood proteins. One is a microfluidic chip to perform quantitative protein analysis on tiny samples, such as a single cell or a pinprick of blood. The other technology is an approach for building stable and high-performance protein capture agents. These have the potential to replace the expensive and unstable antibodies that are currently used in blood protein diagnostics. "Our antibody replacement technology yields chemically synthesized molecules that can serve as antibody equivalents—and, unlike traditional antibodies, they are reproducible in manufacturing.

Beginning in 2009, Kearney, Heath and Hood raised close to $40 million to form Integrated Diagnostics, mostly from InterWest Partners, the Wellcome Trust, and BioTechCube.

Having helped start several companies, including Amgen and Applied Biosystems, "Lee has a start-up success rate of about nine out of ten, so, if you shop around an idea and have Lee on board, everybody opens their doors," Heath says. "We raised enough money to give us a very good chance of success."

Caltech's Office of Technology Transfer provided particular help in filing patent applications and helping in negotiations with Integrated Diagnostics over licensing Heath's intellectual property. "Caltech's Office of Technology Transfer is the best in the country," Heath says. "They strike deals that are fair, and understand how to work with small companies in ways that don't handicap them."

Indi's initial focus is on lung cancer. Typically, in lung cancer diagnostics, a CT scan or ultrasound might reveal pulmonary nodules or masses within the lungs. "But you have no idea if they're benign or malignant, so doctors operate on all of these patients, even though two-thirds of these lesions are typically benign," Heath says. "It's about a $50,000 procedure."

"Indi is pioneering powerful new approaches to blood diagnostics that promise the ability to detect disease early as well as to follow disease progression and response to therapy for individual patients," says Hood. "These are hallmark opportunities for personalized medicine. "

For a product to be successful, however, Heath says that it has to solve both medical and economic problems, because if a fantastic new drug or test is too expensive the medical establishment won't adopt it. "If we can kick out half of those $50,000 procedures for a big provider with millions of clients, then the net result is that we have saved a couple of dollars for every client, and that's a huge annual savings for the provider.  A diagnostic test that can perform that well is considered to be a home run."