Drug PipelineSeries: Phase II --- Oct16-Oct23 2006

Osiris Therapeutics Reports Positive Phase II Results Using PROCHYMAL™ in Treatment-Resistant Crohn's Disease
Osiris Therapeutics announced positive results from a pilot phase II study using PROCHYMAL for the treatment of patients with moderate to severe Crohn's disease who had failed to respond to standard treatments such as steroids and infliximab (Remicade®). In the study, every patient evaluated reported a reduction in Crohn's Disease Activity Index or CDAI after receiving two infusions of PROCHYMAL. There was a statistically significant decrease in mean CDAI scores of 105 points by day 28 from 341 to 236 (p=0.004). The results will be presented by Dr. Jane Onken, Director of the Inflammatory Bowel Disease Clinic and Associate Professor of Medicine at the Duke University School of Medicine at the Annual Meeting of the American College of Gastroenterology on October 24. Dr. Onken was the lead investigator for the trial.

ChemoCentryx Reports Promising Clinical Activity for Traficet-EN® From Phase 2 Trial for the Treatment of Crohn's Disease
ChemoCentryx, Inc., a clinical-stage, biopharmaceutical company developing orally-administered therapeutics that target the chemokine and chemoattractant systems, announced positive data from the company's Phase 2 clinical trial of Traficet-EN® (CCX282-B) for the treatment of Crohn's disease at the 14th United European Gastroenterology Week (UEGW 2006) meeting in Berlin, Germany. Traficet-EN® is a first-in-class, orally active, anti-inflammatory agent that targets the chemokine receptor known as CCR9.
The four-week Phase 2 clinical trial enrolled 74 patients with moderate-to-severe Crohn's disease to primarily assess Traficet-EN's safety and tolerability. Patients were randomized on a 2:1 basis to receive 250 mg of Traficet-EN once daily for 28 days or placebo. Traficet-EN was very well tolerated: incidence of adverse events was approximately similar to those observed in the placebo group. Clear signs of clinical activity, measured by a drop in blood levels of C-reactive protein (CRP) were observed in the patients receiving Traficet-EN compared to placebo.

ZymoGenetics Begins Phase 1/2 Clinical Trial With IL-21 and Nexavar in Patients With Renal Cell Cancer
ZymoGenetics, Inc. announced the start of a Phase 1/2 clinical study of Interleukin 21 (IL-21) in combination with Nexavar® (sorafenib) in patients with advanced renal cell cancer. The study will evaluate the safety and preliminary anti-tumor activity of IL-21 in combination with Nexavar.
The open-label, dose-escalation multi-center U.S. trial is expected to enroll 48 patients with metastatic stage IV renal cell cancer. The Phase 1 part of the study will establish the maximum tolerated dose of IL-21 given for one treatment course, consisting of two 5-day cycles of IL-21 in combination with a standard dose of Nexavar administered over a 6-week period. The Phase 2 part of the study will further evaluate the safety and preliminary anti-tumor activity of IL-21 at the dose established in Phase 1 in combination with Nexavar.

YM BioSciences announces results of AeroLEF™ Phase IIb open-label study
YM BioSciences Inc. announced results from the open-label portion of its Phase IIb trial (DLXLEF-AP4) of AeroLEF™.
The results demonstrated that the majority of the patients were able to achieve effective analgesia for episodes of moderate to severe acute post-surgical pain by self-titrating the amount of medication they inhaled using AeroLEF™. Results of the study were presented at the American Society of Anesthesiologists (ASA) Annual Meeting in Chicago, IL.
AeroLEF is a unique, inhaled-delivery composition of free and liposome-encapsulated fentanyl, in development for the treatment of moderate to severe pain, including cancer pain. AeroLEF is designed to permit patients to match dosage to their individual pain intensity and experience rapid and extended pain relief.
In the study, patient self-titrated dosing with AeroLEF provided clinically meaningful analgesia in 81 percent, 100 percent and 87.5 percent of treated pain episodes during doses 1, 2 and 3 respectively. Within 10 minutes of initiating dosing with AeroLEF, 38 percent, 73 percent and 63 percent of patients reported a reduction in pain intensity to mild pain during doses 1, 2 and 3 respectively. Achieving effective pain relief was the reason for stopping AeroLEF dosing in 35 of 40 (88 percent) treated pain episodes.

AVANIR Announces Publication of Phase II Diabetic Neuropathic Pain Trial Results
AVANIR Pharmaceuticals announced that results of a Phase II clinical trial evaluating escalating doses of Neurodex™ in the treatment of painful diabetic neuropathy were published for the first time in the October issue of Clinical Therapeutics (Vol 28, Number 10, 2006).
The open label trial, conducted at five U.S. sites in 36 patients with painful diabetic neuropathy, assessed the safety and tolerability of Neurodex, a proprietary formulation of dextromethorphan (DM) and low dose quinidine (Q). A preliminary assessment of the drug candidate's efficacy in the treatment of painful diabetic neuropathy was obtained using pain ratings scales and patient diaries. At the end of the study, mean changes from baseline using Pain Intensity Rating Scale and the Pain Relief Rating Scale scores were highly statistically significant (p less than 0.001). Daily patient diary assessments also demonstrated statistically significant improvements in sleep, present pain intensity, activity and pain rating scales (p less than 0.001 in each case).
Adverse events related to Neurodex were mild to moderate and were consistent with the previously known effects of the drug. Adverse events reported included nausea, dizziness and headache. Three patients did not complete the study, two due to adverse events and one due to inability to comply with the protocol. Ninety-two percent of participants completed the study, and 70% of the subjects that completed the study tolerated the maximum allowed dose (60DM/60Q dosed twice per day).

Medivation Begins Phase 1-2a Trial of Dimebon™ in Huntington's Disease
Medivation, Inc. announced that patient dosing has begun for its Phase 1-2a clinical trial of Dimebon™ to treat Huntington's disease.
Medivation is conducting the Huntington's disease trial in collaboration with the Huntington Study Group (HSG), a network of more than 250 experienced clinical trial investigators, coordinators and consultants from more than 60 academic and research institutions throughout the United States, Canada, Europe and Australia. The study will be conducted at approximately 12 HSG sites in the United States and led by principal investigator Karl Kieburtz, M.D., M.P.H., professor of neurology at the University of Rochester and director of the HSG Clinical Trials Coordination Center.
The Huntington's disease clinical trial has two parts: a dose-escalation phase to determine the optimal doses of Dimebon, followed by a three-month randomized, placebo-controlled, double-blinded phase to evaluate the safety and preliminary efficacy of those doses in approximately 75 Huntington's disease patients. The second part of the study will begin after additional animal toxicology studies, requested by FDA and now underway, have been completed. The primary efficacy endpoint in the trial is the Unified Huntington's Disease Rating Scale (UHDRS), and results are expected in the second half of 2007.