PRÉCIS^® Precision Medicine

Patient-specific, clinically relevant response, resistance and pathway information for Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC)

PRÉCIS Non-Small Cell Lung Cancer (NSCLC) Profile

Response Biomarkers

• Predict which patients will likely respond to molecular targeted therapies and
  chemotherapies
• Guide treatment choices to maximize efficacy in NSCLC patient populations

Resistance Biomarkers

• Predict which patients will likely be resistant to specific molecular targeted
  therapies and chemotherapies
• Guide treatment choice towards alternative pathways

Tumor Biomarkers

• Provide information on activated pathways that can be potentially
  targeted with existing therapies and/or direct physicians towards
  appropriate clinical trials
• Guide treatment choice towards alternative pathways new therapies
  and/or combinatorial approach to effectively treat NSCLC

PRÉCIS Colorectal Cancer (CRC) Profile

Response Biomarkers

• Predict which patients will likely respond to anti-EGFR monoclonal antibody
  therapies and chemotherapies
• Guide treatment choices to maximize efficacy in CRC patient populations

Resistance Biomarkers

• Predict which patients will likely be resistant to anti-EGFR
  monoclonal antibody therapies and chemotherapies
• Guide treatment choice towards alternative pathways

Tumor Biomarkers

• Provide information on activated pathways that can be potentially
  targeted with existing anti-EGFR therapies and/or direct physicians
  towards appropriate clinical trials
• Guide treatment choice towards alternative pathways including
  new therapies and/or combinatorial approach to effectively treat CRC

The information provided is not intended to be inclusive of all relevant published clinical studies or open clinical trials. Physicians should incorporate test results with all information available in diagnosing and determining appropriate treatment options for their patients.

PRÉCIS Indications for Use and Limitations
Studies indicate PRÉCIS is useful in tumor specimens from patients diagnosed with non-small cell lung cancer, colorectal cancer, breast cancer, gastric cancer, melanoma, and GIST. Results should be interpreted in conjunction with other laboratory and clinical findings. Performance characteristics refer to the analytical performance of the test. Polymorphisms or mutations at locations not tested (see Methods) that may be associated with drug efficacy or patient outcome will not be detected. bioTheranostics’ policy is to provide physicians with flexibility to choose appropriate tests and to assure that the convenience of ordering a multi-test profile does not prevent physicians from making informed decisions regarding which tests are medically necessary. Each of the tests offered in the bioTheranostics test profile portfolio may be ordered individually using the bioTheranostics Test Requisition. This test was developed and performance characteristics have been determined by bioTheranostics, Inc. It has not been cleared or approved by the U.S. Food and Drug Administration. This test is used for clinical purposes. It should not be regarded as investigational or for research. How this information is used to guide patient care is the responsibility of the physician. bioTheranostics is certified under the Clinical Laboratory Improvement Amendments of 1988 as qualified to perform high complexity clinical laboratory testing.

References for NSCLC Biomarkers

1. Sequist LV et al. Oncologist 2007;12:90-8. 2. Cappuzzo F et al. Crit Rev Oncol Hematol 2006;58:31-45. 3. The NCCN Non-Small Cell Lung Cancer Clinical Practice Guidelines in Oncology (Version 3.2011). National Comprehensive Cancer Network, Inc. 2011. 4. Oxnard GR et al. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. 5. Yasuda H et al. Lancet Oncol. 2012 Jan;13(1):e23-31. 6. Nakamura H. et al. Thorax. 2006 Feb;61(2):140-5. 7. Pirker R. et al. Lancet Oncol. 2012 Jan;13(1):33-42. 8. Shaw AT et al. J Clin Oncol. 2009 Sep 10;27(26):4247-53. 9. Shaw AT et al. Lancet Oncol. 2011 Oct;12(11):1004-12. 10. Choi YL et al. N Engl J Med. 2010 Oct 28;363(18):1734-9. 11. Sasaki T et al. Cancer Res. 2010 Dec 15;70(24):10038-43. 12. Sasaki T et al. Cancer Res. 2011 Sep 15;71(18):6051-60. 13. Doebele RC et al. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. 14. Brose MS et al. Cancer research, 2002. 62(23): p. 6997. 15. Pao W et al. PLoS Med. 2005 Jan;2(1):e17. 16. Bean J et al. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20932-7. 17. Engelman JA et al. Science. 2007 May 18;316(5827):1039-43. 18. Ou SH et al. J Thorac Oncol. 2011 May;6(5):942-6. 19. Chen HJ et al. Pathol Oncol Res. 2009 Dec;15(4):651-8. 20. Sequist LV et al. Sci Transl Med. 2011 Mar 23;3(75):75ra26. 21. Arcila ME et al. Clin Cancer Res. 2011 Mar 1;17(5):1169-80. 22. Turke AB et al. Cancer Cell. 2010 Jan 19;17(1):77-88. 23. Schiller JH et al. J Clin Oncol 28(18 Suppl): abstract, LBA7502. 24. www.clinicaltrials.gov. 25. Okuda K et al. Cancer Sci. 2008 Nov;99(11):2280-5. 26. Cappuzzo F et al. J Clin Oncol. 2009 Apr 1;27(10):1667-74. 27. Go H et al. J Thorac Oncol. 2010 Mar;5(3):305-13. 28. Benedettini et al. Am J Pathol. 2010 Jul;177(1):415-23. 29. Nakamura Y et al. Cancer Sci. 2007 Jul;98(7):1006-13. 30. Spigel et al. J Clin Oncol 29: 2011, 2011. (suppl; abstr 7505). 31. Wang X et al. Med Oncol. 2010 Jun;27(2):484-90. 32. Lee JJ et al. Lung Cancer. 2010 Nov;70(2):205-10. 33. Zheng Z et al. N Engl J Med. 2007 Feb 22;356(8):800-8. 34. Reynolds C et al. J Clin Oncol. 2009 Dec 1;27(34):5808-15. 35. Olaussen KA. et al. N Engl J Med. 2006 Sep 7;355(10):983-91. 36. Seyhan et al. Ann Thorac Cardiovasc Surg. 2011 Apr;17(2):110-7. 37. Tepeli E, et al. Mol Biol Rep. 2012 Jan;39(1):335-41. 38. Roth JA and Carlson JJ. Clin Lung Cancer. 2011 Nov;12(6):393-401. 39. Jiang J et al. Mol Biol Rep. 2012 Feb 3. [Epub ahead of print]. 40. Hammerman PS et al. Cancer Discov. 2011 Apr 3;1(1):78-89. 41. Lee, S.Y et al. J Thorac Oncol, 2010. 5(11): p. 1734-40. 42. Marchetti A et al. J Clin Oncol. 2011 Sep 10;29(26):3574-9l. 43. Hosoya Y et al. Lung Cancer, 1999. 25(2): p. 87-93. 44. Kohno T et al. Genes, Chromosomes and Cancer, 1998. 22(2): p. 152-156. 45. Bepler G et al. Journal of Clinical Oncology, 2004. 22(10): p. 1878. 46. Kawano O et al. Lung Cancer 54, 209-215, 2006). 47. Samuels Y et al. Science. 2004 Apr 23;304(5670):554. 48. Ludovini V et al. J Thorac Oncol. 2011 Apr;6(4):707-15.

References for CRC Biomarkers

1. Amado et al. J Clin Oncol. 2008 Apr 1;26(10): 1626-34. 2. Allegra et al. J Clin Oncol 2009;27:2091-96. 3. Lièvre A et al. Cancer Res. 2006 Apr 15;66(8):3992-5. 4. Di Nicolantonio et al. J. Clin. Oncol. 2008. 26:5705-12. 5. De Roock et al. Lancet Oncol. 2011;12:594-603. 6. Roth AD et al. J. Clin. Oncol. 2010. 28, 466-474. 7. DeRoock W et al. Lancet Oncol. 2010, 11:753-762. 8. Montagut C et al. Nat Med. 2012 Jan 22;18(2):221-3. 9. Negri F et al. Br J Cancer. 2010 Jan 5;102(1):162-4. 10. Chang PM et al. Cancer Sci. 2009 Feb;100(2):278-83. 11. Kim SH et al. Am J Clin Oncol. 2009 Feb;32(1):38-43. 12. www.clinicaltrials.gov. 13. Frattini M et al. Br J Cancer. 2007 Oct 22;97(8):1139-45. 14. Samuels Y and Waldman T. Curr Top Microbiol Immunol. 2010;347:21-41. Review. 15. Sartore-Bianchi A et al. Cancer Res. 2009 Mar 1;69(5):1851-7.