Successfully reported this slideshow.

Organ Specific Proteomics


Published on

Organ Specific Proteomics as Presented by Paul Kearney, PhD; CSO, Integrated Diagnostics at the 2010 Personalized Health Care National Conference at Ohio State.

  • Be the first to comment

  • Be the first to like this

Organ Specific Proteomics

  1. 1. Realizing P4 Medicine: First Steps <br />Paul Kearney, Ph.D.<br />President, CSO and Founder<br />Integrated Diagnostics<br />October 14, 2010<br />1<br />
  2. 2. Integrated Diagnostics<br />Spin out from the Institute for Systems Biology and based in Seattle.<br />Founded September 2009 raising $30M in venture capital from InterWest, Wellcome Trust and BioTechCube.<br />Focus is on the development of early diagnostics for lung cancer and Alzheimer’s.<br />Founding concepts include large scale system measurements and organ-specific proteins.<br />2<br />
  3. 3. The Power of Vision: The First Step<br />3<br />enables<br />The value of visionary ideas, such as P4 medicine, is that they <br />compel us (researchers, policy makers, entrepreneurs, etc.) <br />to innovate and take those important first steps to realizing the vision.<br />Advances in<br />technology, policy, knowledge<br />Visionary Idea<br />compels/directs<br />
  4. 4. The Power of Vision: The First Step<br />4<br />first steps<br />longer term<br />The Vision: Location Awareness<br /><ul><li> self-navigating cars
  5. 5. Raytheon (1950s)</li></ul>Personal GPS Devices<br /><ul><li> car navigation devices
  6. 6. cell phone location apps
  7. 7. portable devices (iPad)</li></ul>GPS ($12B, 1970s)<br /><ul><li> enabling tech</li></ul>Google’s self navigating car <br />
  8. 8. The Power of Vision: The First Step<br />5<br />first step<br />longer term<br />P4 Medicine <br /><ul><li> system wellness assays
  9. 9. monitor thousands of markers
  10. 10. from a drop of blood.</li></ul>?$<br />Today<br />The first step is tactical: <br /> What can we do tomorrow with today’s innovations?<br />
  11. 11. Some ‘First Step’ Challenges for P4 Medicine<br />6<br />Technology<br />Technology<br /><ul><li> Need for massively parallel measurements
  12. 12. Reducing ‘Loss in Translation’</li></ul>Commercialization<br /><ul><li> Developing market channels
  13. 13. Working within the existing environment
  14. 14. Adoption by clinicians</li></ul>Clinical<br /><ul><li> Identifying the right clinical problems
  15. 15. Acquiring high value content markers
  16. 16. Regulatory hurdles</li></ul>P4<br />Commercial<br />Clinical<br />What has Integrated Diagnostics done to address these challenges?<br />
  17. 17. Challenge #1: Finding the Right Application<br />7<br />Determine if a lung cancer lesion detected <br />by imaging is benign or malignant.<br />Patrick Nana-Sinkham, MD The Ohio State University School of Medicine<br />
  18. 18. What Makes This Application Ideal?<br />estimated 2.7 million lung lesions are seen by imaging every year in the US<br />current protocol is ‘watchful waiting’<br />if the lesion grows (operate – ~30% error rate) or<br />if the lesion does not grow after 2 years then do nothing (97% of cases; 4-5 CT scans per patient on average)<br />hard to biopsy (blood-based Dx test is ideal)<br />market research indicates that this is the #1 diagnostic need in lung cancer among pulmonologists (the end-users)<br />High unmet need drives <br />adoption of new ideas, technologies and solutions.<br />8<br />
  19. 19. Challenge #2: Intelligently Selecting Markers to Monitor<br />1. Lung-specific proteins (expressed only by the lung) *<br />Sentinels of system health and disease of the lung only<br />Lung-specific proteins are highly modulated by lung disease (statistical disease association analysis across GEO database)<br />2. Lung cancer tumor-specific cell surface markers **<br />Proteins expressed on the cell-surface of tumor cells but not healthy cells<br />Likely to be found in blood.<br />3. Lung cancer tumor-specific secreted proteins **<br />Proteins secreted by tumor cells but not by normal cells<br />Likely to be found in blood.<br />9<br />Total: ~750 proteins<br />* licensed from the Institute for Systems Biology<br />** licensed from Caprion Proteomics<br />
  20. 20. Challenge #3: Massively Parallel System Measurements<br />Diagnosing/monitoring/treating complex diseases in a complex system (humans) with high population variability requires broad sampling across organs, pathways, biological functions, etc. One gene or one protein is not enough for a high resolution picture of an individual’s state of health.<br />Massively parallel biological system queries are going to be the norm for P4 medicine<br />10<br />
  21. 21. Challenge #3:The Power of Massively Parallel System Measurements<br />11<br />As the number of random blood analytes profiled increases, <br />segregation of healthy and disease type occurs.<br />
  22. 22. Challenge #3:Select a Technology that can Assay 750 Proteins<br />MRM (Multiple Reaction Monitoring) is targeted, hypothesis driven mass spectrometry<br />Focusing resources of the MS on a small number of proteins, not on sample surveys<br />Emerging clinical tool pioneered at Institute for Systems Biology<br />Largest lung cancer assay ever created (750 proteins)<br />12<br />
  23. 23. Challenge #4: Avoid ‘Loss in Translation’<br />‘Loss in Translation’ occurs when discovery results cannot be translated into clinical tools.<br />discovery technology platforms (e.g. mass spectrometry) differ from commercial platforms (e.g. Luminex assays)<br />technologies vary greatly in performance and in what they can detect and measure reliably<br />often large panels of discovery-stage markers cannot be translated onto a commercially viable platform because of cost or multiplexing limitations <br />Solution: Use the same platform technology (mass spec)<br /> discovery  validation  commercialization<br />13<br />
  24. 24. Tactical First Step Solutions<br />14<br />Market<br />Research<br />Discovery<br />Studies<br />MRM Assay Development<br />Validation<br />Studies<br />Commercial-<br />ization<br />1<br />2<br />3<br />4<br />Select an indication of large market size and of high clinical unmet need. Validate with front line clinicians (end-users).<br />License large systems-based discovery data sets.<br />Select a highly multiplexed technology platform (MRM) that enables massively parallel system measurements.<br />Select a technology platform (MRM) that avoids ‘loss in translation’.<br />100+ of the 750 MRM assays developed to date (completed in 6 months)<br />76% success rate in assay development<br />~ $2000 per MRM assay to develop<br />high correlation between discovery data and assay verification data<br />
  25. 25. Other Challenges …<br />Regulation of IVDMIA Dx tests<br />Developing a market channel to end users (e.g. pulmonologists)<br />New use of MRM in the clinic (previously only used for single analyte monitoring such as vitamin D levels).<br />Working within the existing environment. Who saves and who gains with each P4 innovation?<br />15<br />
  26. 26. Concluding Remarks<br />What are the first steps for the P4 vision?<br />What are the demonstration projects?<br />What are the emerging technologies that can be leveraged?<br />What are the performance measures for P4 Medicine?<br />What are the challenges that must be overcome in these demonstration projects?<br />16<br />