Non-Invasive Array Based Screening for Cancer. Dr. Amit Kumar President and CEO CombiMatrix Corporation

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1 Non-Invasive Array Based Screening for Cancer Dr. Amit Kumar President and CEO CombiMatrix Corporation May 13, 2009

2 This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the recent economic slowdown affecting technology companies, our ability to successfully develop products, rapid technological change in our markets, changes in demand for our future products, legislative, regulatory and competitive developments and general economic conditions. Acacia Research: CombiMatrix Annual Report on Form 10-K, recent and forthcoming Quarterly Reports on Form 10-Q, recent Current Reports on Forms 8-K and 8-K/A, and other SEC filings discuss some of the important risk factors that may affect our business, results of operations and financial condition. We undertake no obligation to revise or update publicly any forward-looking statements for any reason. Reform Act Notice

3 Outline of Presentation Background on Company Background on Cancer Technology Comprehensive Cancer Array (CCA) Data Next Steps and Conclusions

4 Company Background NASDAQ: CBMX Corporate Headquarters near Seattle, WA CLIA Laboratory in Irvine, CA Two DNA Array Platforms Bacterial Artificial Chromosome Arrays (BAC-Arrays) Oligonucleotide Arrays Leader in DNA Array Diagnostics and Personalized Medicine More diagnostic products than all array companies combined Favorable FDA opinion Non-Invasive Cancer Screen In Development

5 Background on Cancer Most cancers (especially solid tumors) can be treated if caught early. 5-year survivability is highest for early diagnosis and intervention Poor survivability for late stage and metastasis Cancers with poor 5-year survivability are diagnosed at late stage because symptoms occur at later stages. Ovarian (Only 1 out of 5 alive, in 5 years) Pancreatic Even other cancers if missed at early stage (breast, colon) Diagnosing Cancer Early is Challenging-Good Screening Approaches Are Few Breast Cancer - self exams, mammograms Prostate Cancer - Prostate Specific Antigen (PSA) - non-invasive Other Screening Processes are Invasive, Unpleasant or Expensive Sigmoidoscopy, Colonoscopy Biopsies

6 Holy Grail of Cancer Screening Broad, Comprehensive Cancer Screen Non-Invasive- Blood Test Screens for Multiple Spurious Growths Simultaneously Specify organ/tissue Early Indication Confirm with other Invasive Method Not a guaranteed diagnosis, but an indicator of concern - verify with other method (like PSA-Prostate Specific Antigen test) This would be a revolutionary test with massive public health impact and tremendous market potential.

7 Categories of Tests Pre-Disposition Risk Factor Big Market Inexpensive Expensive Dev. Payer Issues Screening Early Detection Big Market Economic Impact Diagnosis Traditional Smaller Market Prognosis Clinical Course Preventative Medicine Companion Dx Drug Response Number of Patients Decreases in This Direction Monitoring Progression Treatment Response Recurrence CBMX has tests on Market in Prognosis, and is Developing Screening Test Today s Presentation Focuses on Screening Test

8 CBMX Oligonucleotide Array Technology

9 DNA MicroArrays Analyze multiple biomarkers simultaneously Microarray

10 CBMX- Oligonucleotide Array Technology Active Semiconductor Scalable Manufacturing Costs Rapid Customization Discrete Electrodes In Situ E-chem Synthesis SOFTWARE CONTROLLED REACTIONS

11 Virtual Flask Technology Electrochemically Generated Acid Dye = Acid ph Dye = Neutral ph Porous Reaction Layer on Chips Conditions Identical on Both Chips

12 START

13 DEPROTECT

14 COUPLE

15 WASH

16 DEPROTECT

17 COUPLE

18 WASH

19 DEPROTECT

20 COUPLE

21 WASH

22 DEPROTECT

23 COUPLE

24 WASH

25 Three Major Differentiating Characteristics of CBMX Array Technology Arrays Quick, Inexpensive Fabrication Bench Top Synthesizer In-house Array Fabrication Electro-Chemical Detection (ECD) Enables Revolutionary Inexpensive, Compact Instruments

26 How Can We Screen for Growths Early and Identify Organ of Interest? We know that tumors are constantly spilling cellular contents into blood. Cells that break up Organelles Proteins Nucleic Acids We also know that some of these contents are unique to the tumor. However, when tumor is small, the amount of these components in blood is very low and difficult to detect.

27 Past Attempts Previous attempts have focused on measuring contents, but often they are too low in abundance to detect, or are broken down rapidly, or both. Circulating Tumor Cells - usually can be identified once the tumor is relatively large. Organelles - Broken down quickly. Proteins - Low concentrations, broken down quickly. Some notable successes - PSA for Prostate Cancer Nucleic Acids - Low concentration, broken down quickly. DNA mrna- messenger RNA Great focus on nucleic acids --- they can be amplified

28 CBMX Approach New Type of Nucleic Acid Discovered mirna - microrna Small sequence of regulatory RNA CBMX has made mirna arrays for 3 years Two Characteristics of mirna mirna Patterns are unique for each cancer Much more stable in blood than DNA or mrna Hypothesis: We can identify mirnas in Blood that indicate a spurious growth somewhere else in the body

29 Comprehensive Cancer Array Colon Lung Prostate Probes Common All Cancers Each segment carries specific probes that bind to mirnas from blood that are characteristic of different tumor growths with appropriate controls (red).

30 DATA

31 SIGNAL INTENSITY CBMX Arrays Are Very Sensitive CBMX Microarrays can see signal down to 4,000 copies/µl of serum This level of sensitivity is sufficient to perform this assay in blood COPIES PER MICROLITER SERUM

32 Blood Based Profile: Prostate vs. Normal (male) 5 3 prostate normal 1 mir-16 mir-92a mir-103 mir-107 mir-197 mir-34b mir-328 mir-485-3p mir-486-5p mir-92b mir-574-3p mir-636 mir-640 mir-766 mir-885-5p -1-3 We can distinguish Prostate Cancer form Normal ln ratio

33 Blood Based Profile: Ovarian vs. Normal (female) 5 Ov arian Normal 3 1 mir-197 mir-34b mir-328 mir-326 mir-483-5p mir-483-3p mir-485-3p mir-92b mir-596 mir-615-3p mir-636 mir p mir-766 mir-885-5p -1-3 We can distinguish Ovarian Cancer form Normal ln ratio

34 Blood Based Profile: Colon vs. Normal (male and female) Male Female Colon Normal 5 3 Colon Normal mir-92a mir-198 mir-34b mir-423-5p mir-483-5p mir-485-3p mir-574-5p mir-574-3p mir-663 mir p mir-766 mir-765 mir-937 m i R m i R b m i R m i R m i R m i R p m i R p m i R b m i R p m i R p m i R m i R p m i R m i R p m i R We can distinguish Colon Cancer form Normal

35 mir-16 mir-92a mir-197 mir-30b mir-125b mir-34b mir-483-3p mir-491-3p mir-574-3p mir-605 mir-647 mir p mir-1296 mir Blood Based Profile: Breast vs. Normal (female) Breast Normal We can distinguish Breast Cancer form Normal

36 Blood Based Profile: Lung vs. Normal (small cell and NSC) 5 3 Lung Normal 1 mir-92a mir-197 mir-212 mir-342-3p mir-346 mir-423-5p mir-92b mir-574-3p mir-596 mir-631 mir-636 mir-637 mir-654-3p mir-671-3p mir-1296 mir-885-5p -1-3 We can distinguish Lung Cancer form Normal

37 Decision Process SAMPLE No Indication of Cancer Expression Pattern Indicates Problem Detailed Analysis of Pattern No Further Workup Identify Potential Organ System Further Work-up by Physician

38 Clustering Analysis NORMAL CANCER SERUM SAMPLES Normals cluster together, Cancers cluster away from normals Types of cancer cluster together, in general, but more distinction is needed

39 CCA-Timeline Q3-09 Q4-09 Q Research and Development Assay Dev. Protocols QC Metrics Clinical Trials Launch Additional Trials Product Expansion

40 Conclusions Array is Sensitive Enough Can Distinguish Cancer vs. Normal for 5 cancers Initial Focus Breast, Lung, Colon, Ovarian, Prostate 85% of all solid tumors in these categories Evaluated over 100 normal and cancer patients Stage 1-4 Focused on Distinguishing Specific Cancers Decision Tree Approach

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