Studies Show Crescendo Bioscience's Vectra™ DA Multi-Biomarker Test Algorithm More Accurate Than Other Established Disease Activity Measures in Identifying Rheumatoid Arthritis Patients at Risk for Joint Damage Progression

November 5, 2011

Multi-Biomarker Blood Test for RA data presented at the 2011 American College of Rheumatology and Association of Rheumatology Health Professionals’ Annual Scientific Meeting

CHICAGO--Crescendo Bioscience® today announced data indicating that the Company’s multi-biomarker blood test for rheumatoid arthritis (RA) disease activity, Vectra™ DA , may more accurately identify RA patients at risk for progression of joint damage when compared to established disease activity measures. Data demonstrate the Vectra DA algorithm score can identify patients at higher risk for structural damage despite achieving remission by DAS28CRP (the 28-joint disease activity score based on C-reactive protein). Among RA patients in DAS28CRP remission, those who also had a high Vectra DA algorithm score were 2.3 times more likely to have progressive joint destruction during the next year. Moreover, patients in remission as defined by the Vectra DA algorithm score had a lower observed rate of radiographic progression compared to patients in remission by DAS28CRP or by the American College of Rheumatology and the European League Against Rheumatism [ACR/EULAR] Boolean criteria. These and other data are being presented at the American College of Rheumatology and Association of Rheumatology Health Professionals’ Annual Scientific Meeting in Chicago, November 5 – 9, 2011.

“Being able to measure disease activity as well as identify patients at risk for progression of structural damage is critical when treating and managing patients with RA,” said Jeffrey Curtis, MD, MS, MPH, Associate Professor of Medicine, University of Alabama at Birmingham. “Vectra DA may help rheumatologists determine which patients are at higher risk for progression of structural damage.”

Rheumatologists commonly use a combination of clinical assessment, x-rays and laboratory tests to help determine the risk of progression of structural damage. Vectra DA represents a novel, precise and objective blood test that may provide rheumatologists with expanded insights into disease activity and progression of structural damage.

“There is increasing evidence that early, aggressive treatment of RA can lead to improved outcomes and remission,” said David Chernoff, MD, Crescendo Bioscience’s chief medical officer. “As a result, it is crucial that reliable indicators of disease activity are used to track a patient’s status over time. The data being presented during the American College of Rheumatology Conference further demonstrate the promise of Vectra DA in accurately identifying patients who are at risk for progression of structural damage, despite having achieved clinical remission.”

Other data presented during the American College of Rheumatology conference indicate the Vectra DA algorithm score is associated with disability in early RA patients and can differentiate between low disease activity and remission. In addition, data from a study in a Japanese population with RA treated with anti-tumor necrosis factor (anti-TNF) therapies show the ability of the Vectra DA algorithm score to measure disease activity and track response to therapy is consistent with prior studies in North American and European populations.

Additional studies demonstrate that multi-biomarker models may be better predictors of progressive structural damage in RA than clinical measures and initial observations indicate that profiles of autoantibodies reactive to individual peptides may differ among immunoglobulin isotypes. Future studies will evaluate if auto-immune responses to these individual peptides will help assess the risk of structural damage.

RA is a debilitating, highly variable, chronic disease that often results in joint damage and disability. Vectra DA is the first and only multi-biomarker blood test to assess RA disease activity, integrating information from 12 key biomarkers into a single objective score.

Overview of Vectra DA Algorithm Data

Oral Presentation

A Multi-Biomarker Disease Activity (Vectra™ DA) Algorithm Score for Rheumatoid Arthritis Predicts Radiographic Progression in the BeSt Study (W 474 A, McCormick Place West, Oral Presentation 1613: November 7, 2011; 3:00 p.m. CST)

Researchers analyzed blood samples from baseline and year one of 126 patients from the Behandel Strategieën (BeSt) clinical study to determine whether the Vectra DA algorithm score helps predict progressive joint damage. Disease activity is a significant risk factor for joint damage.

The Vectra DA algorithm score was significantly associated with joint damage progression (p< 0.001). In a multivariate regression analysis including other disease activity measurements, only the Vectra DA algorithm score was a significant predictor of the second year change in van der Heijde Sharp Score, a common radiographic scoring method used to assess joint damage in RA (p< 0.05).

Poster Sessions

Evaluation of Definitions of Rheumatoid Arthritis Remission by Assessing Radiographic Progression in the Leiden Early Arthritis Cohort (Poster Session, Presentation 323: November 6, 2011; 9:00 a.m. – 11:00 a.m. CST)

The prognostic values of three different definitions of RA remission (ACR/EULAR Boolean, DAS28CRP, and Vectra DA Algorithm Score) were assessed to determine whether Vectra DA algorithm scores can augment existing classifications of remission. Vectra DA algorithm scores and other variables were assessed at 271 study visits among patients in the Leiden Early Arthritis Cohort, a Dutch population-based cohort. Patients in remission, according to the Vectra DA algorithm score, had lower observed rates of radiographic progression over one year compared to patients in DAS28CRP remission or ACR/EULAR Boolean remission. Among RA patients in DAS28CRP remission, those who also had a high Vectra DA algorithm score were 2.3 times more likely to have progressive joint destruction during the next year. These results suggest Vectra DA may be useful in identifying patients who remain at risk for structural damage despite achieving DAS28CRP-defined remission. Vectra DA disease activity categories may better discriminate a patient’s risk for structural damage progression than DAS28CRP disease activity categories.

A Novel Multi-Biomarker Disease Activity Score (Vectra™ DA algorithm score) Reflects Clinical Disease Activity Score and Health Assessment Questionnaire for Rheumatoid Arthritis in the BeSt Study (Poster Session, Presentation 351: November 6, 2011; 9:00 a.m. –11:00 a.m. CST)

Blood samples were analyzed from 125 RA patients at 179 visits in the BeSt study. The Vectra DA algorithm score was significantly correlated with clinical disease activity (DAS28; p< 0.001). In addition, change in the Vectra DA algorithm score was significantly correlated with change in DAS28 between baseline and year 1 study visits, showing that the Vectra DA algorithm can track changes in disease activity over time. Further, the data demonstrated that the correlation between the Vectra DA algorithm score and the Health Assessment Questionnaire (HAQ) Disability Index (DI) was statistically significant (p < 0.001). In addition, those patients with a low Vectra DA algorithm score at year 1 had a significantly higher rate of HAQ remission than those with a moderate or high Vectra DA algorithm scores (p=0.041).

These results demonstrate that the Vectra DA algorithm score can measure current disease activity and track changes over time. In addition, the Vectra DA algorithm score results demonstrate an association with disability in early RA patients.

Investigation of a Multi-Biomarker Disease Activity (Vectra DA) Signature and Algorithm Score in Rheumatoid Arthritis Patients with Low Disease Activity: The REMIRA Study (Poster Session, Presentation 361: November 6, 2011; 9:00 a.m. – 11:00 a.m. CST)

Blood samples from the UK based REMIRA (Remission in RA) study acquired at baseline from 70 RA patients on stable therapy with disease duration of less than 10 years and DAS28 of less than 3.2 were examined to determine whether Vectra DA could differentiate between low disease activity and remission. Multiple definitions of remission were assessed, including those for standard clinical disease activity scores (DAS28, CDAI, SDAI) and the new ACR/EULAR Boolean criteria. A statistically significant association (p< 0.01 in all cases) was observed between the Vectra DA algorithm score and the current clinical standards for evaluating RA remission vs. non-remission. These results demonstrate that the Vectra DA algorithm score can differentiate between low disease activity and remission.

A Multi-Biomarker Disease Activity Score (Vectra™ DA algorithm score) Reflects Clinical Disease Activity and Tracks Response in a Japanese Rheumatoid Arthritis Population Treated with Anti-TNF Therapy (Poster Session, Presentation 2244: November 8, 2011; 9:00 a.m. – 11:00 a.m. CST)

Among 147 patients enrolled at the University of Occupational and Environmental Health in Japan receiving anti- tumor necrosis factor treatment, the Vectra DA algorithm score was significantly associated with clinical disease activity (DAS28, p<0.001). In the Vectra DA algorithm, the 11 biomarkers other than CRP provided information about disease activity that was not available from CRP alone. Change in the Vectra DA algorithm score was associated with clinical response to therapy. These results suggest that the Vectra DA algorithm score has a similar relationship to disease activity in both Caucasian and Japanese populations. Additionally, these results show that the Vectra DA algorithm score provides added value about disease activity above that provided by CRP and confirm the association with disease activity seen in other studies.

Presentations on Other Biomarker Tests

Oral Presentation

Development of A Multi-Biomarker Structural Damage Score in Rheumatoid Arthritis to Predict Radiographic Progression in the Leiden Early Arthritis Cohort (W 375 B, McCormick Place West, Oral Presentation 838: November 6, 2011; 4:45 p.m. CST)

Researchers evaluated both individual biomarkers and prototype multi-biomarker models to assess the association to joint damage in RA patients over 12 months. Biomarker concentrations were determined in 307 blood samples from 187 patients in the Leiden Early Arthritis Cohort, a Dutch population-based cohort.

The study found that multi-biomarker models had higher observed performance than conventional clinical measures at predicting progressive structural damage in RA. A multi-biomarker test, if validated, has the potential to help predict structural damage in clinical practice.

Poster Session

Development of a High-Throughput, Multiplex Assay for Profiling the Autoantibody Fine Specificity in Rheumatoid Arthritis (Poster Session, Presentation 1748: November 8, 2011; 9:00 a.m. –11:00 a.m. CST)

Serum samples from 35 RA patients with different disease activity levels were evaluated for the presence of autoantibodies. Reactivity to a panel of novel peptides derived from multiple proteins was assessed along with anti-cyclic citrullinated peptide reactivity and rheumatoid factor status. Initial observations indicate that profiles of autoantibodies reactive to individual peptides may differ among immunoglobulin isotypes (IgG, IgM, etc) and further evaluation may provide insight into progression of structural damage.

About Rheumatoid Arthritis
Rheumatoid arthritis is a debilitating, highly variable, chronic disease affecting approximately 1.5 million Americans and more than 2 million people in Europe. The primary symptoms of RA are joint inflammation, pain, and fatigue, with the disease often resulting in joint damage and disability. RA is a systemic, inflammatory disease that can significantly damage other parts of the body and result in diseases such as cardiovascular disease, a leading cause of death for RA patients.

About Vectra™ DA
Vectra DA is a quantitative, objective and reproducible multi-biomarker blood test that provides physicians a wide spectrum of insights into the biology of rheumatoid arthritis. This test measures 12 key serum biomarkers and integrates them into an easy to interpret score to help guide patient management and complement clinical decisions throughout the disease course. Vectra DA testing is performed at Crescendo Bioscience’s state-of-the-art CLIA (clinical laboratory improvement amendments) facility and test results are reported back within 7-10 days of receipt of sample. Physicians can either receive test results via standard report forms or via the private web portal, VectraView. For more information on Vectra DA, please visit, www.Vectra-DA.com.

About Crescendo Bioscience, Inc.
Crescendo Bioscience is a molecular diagnostics company focused in rheumatology and located in South San Francisco, CA. Crescendo Bioscience develops quantitative, objective, biology-based tests to provide rheumatologists with deeper clinical insights to help enable more effective management of patients with autoimmune and inflammatory diseases. For more information, please visit the company’s website at www.CrescendoBio.com.