CRx-102

In a poster entitled "Inhibition of Macrophage and Chondrocyte Inflammatory Mediators by CRx-102, a Novel Synergistic Combination Drug Candidate", Fraser, et.al. further insights into the novel mechanism of action of CRx-102 were unveiled. The synergistic combination of the two agents, dipyridamole and prednisolone, was found to modulate converging intracellular signaling pathways to synergistically inhibit key inflammatory modulators and mediators (TNF-alpha, MIP-1a, RANTES, MDC, IL-6 and MMP-9) that control disease progression and contribute directly to disease pathology.

In a poster entitled "Response and State-Attainment Criteria in Hand OA: Analysis from a Placebo-Controlled Clinical Trial of CRx-102, A Novel Synergistic Combination Therapy", Kvien, et.al., reliable outcome measures to evaluate clinically meaningful benefits of CRx-102 treatment in osteoarthritis (OA) from an individual patient perspective were evaluated. CRx-102 consistently showed clinically meaningful benefit across these outcome measures and responder analyses:

• BLISS response of individual pain of less than or equal to 20 (27% CRx-102 vs. 6% placebo, p=0.035)
• Modified OMERACT-OARSI response (50% CRx-102 vs. 30% placebo, p=NSS)
• AUSCAN 20/50/70 (AUSCAN 70: 23% CRx-102 vs. 3% placebo, p=0.037)

    In a satellite symposium presentation, Dr. John Kirwan, of the Bristol Royal Infirmary in the UK and principal investigator in the CRx-102 phase 2a rheumatoid arthritis (RA) trial, gave a talk entitled "A Therapy Rejuvenation: Glucocorticoids in Arthritis". Additional analysis from the trial indicated that CRx-102 treated patients experienced significantly less fatigue than those on placebo (-27.2mm CRx-102 vs. -14.3mm placebo, p=0.03). Fatigue information was collected on all subjects in the trial and was measured using a visual analog scale (VAS).

"This data on CRx-102 provides additional evidence of its clinical benefit and novel mechanism of action which will prove extremely helpful as we design future studies and more specifically define the clinical benefit of CRx-102 and its potential role within the RA and OA treatment paradigms," commented Alexis Borisy, President and CEO of CombinatoRx.

CRx-139

    Also, during the satellite symposium, Dr. Paul Emery of Leeds Teaching Hospital in the UK gave a talk entitled "Inverting the Pyramid, Deploying Smarter Combination Therapies in RA", during which he presented additional analysis from the recently completed phase 2a clinical trial of CRx-139. Dr. Emery showed that subjects treated with high dose CRx-139 (3mg of prednisolone and 20mg of paroxetine) showed a benefit in ACR 50 response compared to low dose CRx-139 (3mg of prednisolone and 10mg of paroxetine) or 3mg of prednisolone alone.

• ACR 50 at day 42 (32% CRx-139 high dose vs. 13% CRx-139 low dose and 13% 3mg prednisolone, p=0.008)
• ACR 50 at day 70 (28% CRx-139 high dose vs. 15% CRx-139 low dose and 20% 3mg prednisolone, p=NSS)

    Dr. Emery also noted that a subset of the high dose treated patients experienced durable remission defined as DAS28 score of less than 2.6 at consecutive visits (19% CRx-139 high dose vs. 4% CRx-139 low dose and 3% 3mg prednisolone, p=0.026).

About CRx-102

CRx-102 is an oral synergistic combination drug candidate containing the cardiovascular agent dipyridamole and an unconventionally low dose of the steroid prednisolone. CRx-102 works through a novel mechanism of action in which dipyridamole selectively amplifies prednisolone's anti-inflammatory and immunomodulatory activities without replicating its side effects. In phase 2 clinical trials, CRx-102 demonstrated a powerful anti-inflammatory effect and rapid onset of action in patients with osteoarthritis and rheumatoid arthritis, and was generally well tolerated. CRx-102 is being developed in a modified-release commercial formulation for the treatment of multiple immuno-inflammatory diseases.