Drug Pipeline Series: Phase II, Oct23-Oct30, 2006

OREXIGEN REPORTS RESULTS FROM STUDY OF OBESITY DRUG
Orexigen Therapeutics announced that Excalia, a combination of two centrally acting medications intended to provide and sustain clinically important weight loss, demonstrated significant weight loss in a six-month, double-blind, Phase IIa clinical study. The magnitude of weight reduction exceeded that seen with placebo. The findings showed that patients completing the blinded 24-week phase lost on average 9.2 percent of their weight from baseline using Excalia compared with an average of 0.4 percent weight loss from baseline for patients using placebo. The study results further demonstrate that weight loss continued through an additional 24-week open-label period, with Excalia patients achieving an average weight loss of 12 percent from baseline by 48 weeks.
Excalia is a proprietary combination of bupropion, a dopamine and norepinephrine reuptake inhibitor, plus zonisamide, an approved anticonvulsant medication. The company's preclinical research suggests that combining these two central nervous system drugs acts on a complex of neurons in the hypothalamus, the area of the brain contributing to the regulation of appetite, energy output and maintaining body weight. The compound was tested in a double-blind, placebo-controlled, randomized, proof-of-concept Phase II clinical study of 127 non-smokers with body mass indices (BMI's) between 30 and 40.

RENOVO REPORTS POSITIVE RESULTS FROM SCAR-REDUCTION TRIAL
Renovo has announced positive Phase II clinical trial results for its lead drug, Juvista, in a 12-month proof-of-concept study of scar reduction at split-thickness skin graft donor sites.
Juvista is a therapeutic application of human recombinant TGFß3, which has been shown in clinical trials to markedly improve subsequent scar appearance in the skin. The trial was a fully randomized, double-blind, placebo-controlled study designed to investigate the safety, tolerability, systemic exposure and anti-scarring potential of Juvista in split-thickness skin graft donor sites. Clinical assessment by plastic surgeons at 12 months following administration of Juvista demonstrated a statistically significant reduction in scarring compared with placebo and indicated a permanent regeneration of more normal skin. This trial demonstrates, for the first time, the efficacy of Juvista in the reduction of scarring in large open wounds whose margins are not approximated and sutured.
Juvista was effective given as an injection followed by topical application at the time of surgery and topical application one day later. The study was the first time Juvista has been administered to open wounds and is in contrast to previous trials in incisional wounds closed by suture or steri strips.
Development of a topical formulation of Juvista would offer the prospect of additional indications such as reducing scarring in split thickness skin graft donor sites, grafts and burns which are markets of high medical need. Juvista injection for closed wounds following incisions/excisions, however, remains Renovo's primary target market as this represents the vast majority of surgical procedures.

ViroPharma and Wyeth Initiate Dosing in Phase 2 Study of HCV-796 in Treatment Naive Patients and Non-Responders
ViroPharma Incorporated announced that patient dosing has commenced in a Phase 2 study of HCV-796, a unique orally dosed hepatitis C viral polymerase inhibitor that interferes with the replication of hepatitis C virus (HCV).
The Phase 2 study is being conducted with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), ViroPharma's partner in development of HCV-796.

The objectives of this trial are to assess the safety, tolerability, pharmacokinetic profile, and antiviral activity of HCV-796, when used in combination with pegylated interferon alfa-2b plus ribavirin compared to the current standard of care in treatment-naive subjects with HCV genotype 1 infection and in patients with HCV genotype 1 infection who were non-responders to prior HCV therapy. The companies will add an additional dose or doses of HCV-796 to the trial to further elucidate the dose response.

MethylGene Initiates Phase I/II Combination Clinical Trial with its Proprietary HDAC Inhibitor, MGCD0103, and Gemzar'R' in Patients with Pancreatic Cancer
MethylGene Inc., along with its partner Pharmion Corporation, announced the initiation of a Phase I/II clinical trial (Trial 006) evaluating its isotype-specific histone deacetylase (HDAC) inhibitor product candidate, MGCD0103, in combination with Gemzar® (gemcitabine HC1; Eli Lilly and Company) in patients with solid tumors, including pancreatic cancer. Gemzar is an approved chemotherapy, marketed for use in pancreatic, non-small cell lung, breast and ovarian cancers.
In the Phase I portion of this open-label trial, MGCD0103 will be given orally, three times per week for four weeks in combination with Gemzar, which will be administered intravenously once per week for three weeks out of four in patients whose cancers are eligible to be treated with Gemzar, or patients who have no available standard of care. Key objectives for this portion of the study will be to evaluate the compatibility and safety of administering these two agents together, to determine the maximum tolerated dose of MGCD0103 and to define the Phase II dose to be administered in this combination. Secondary objectives include determining the dose-limiting toxicities, objective responses, time to progression, survival, and the pharmacodynamic and pharmacokinetic characteristics. In the expanded Phase II portion of the trial, the primary objective is to determine the overall response rate in pancreatic cancer patients. The trial may enroll up to 60 patients at cancer centers in North America. The trial is expected to take 18 to 24 months to complete.

EntreMed Commences Clinical Trial for MKC-1 in Lung Cancer Patients
EntreMed, Inc. announced commencement of a multi-center study with its drug candidate, MKC-1, in non-small cell lung cancer (NSCLC) patients. The lead institution for this Phase 1/2, open label, dose escalation study will be the Indiana University Cancer Center in Indianapolis, Indiana. Nasser H. Hanna, M.D., Assistant Professor, Department of Medicine, Division of Hematology/Oncology at IUCCI, will serve as Principal Investigator. MKC-1 is being evaluated currently in Phase 1 and 2 clinical studies against breast cancer and in patients with leukemia.

The objective of the Phase 1 portion of this study will be to assess the safety and maximum tolerated dose of MKC-1 when administered orally in combination with pemetrexed (Alimta®). Alimta® is a multi-targeted antifolate, which blocks the activity of folic acid and is approved for the treatment of metastatic NSCLC.
The Phase 2 component of this study will assess the antitumor activity and progression free survival (PFS) in up to 60 patients with non-small cell lung cancer. Patients whose disease has progressed following initial therapy may be eligible to enroll. Patients will receive orally administered MKC-1 in combination with pemetrexed (Alimta®). A secondary endpoint of the Phase 2 study will be to evaluate other parameters of antitumor activity including response duration and overall survival.
MKC-1 is a novel, orally active cell cycle inhibitor with in vitro and in vivo efficacy against a wide range of human solid tumor cell lines, including multi-drug resistant cell lines. MKC-1 has demonstrated broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple animal models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M- phase (mitosis) of the cell cycle, and induce apoptosis. These effects are consistent with a mechanism resulting from MKC-1 binding to multiple intracellular targets, including tubulin and the importin beta proteins. The importin beta family of proteins plays a critical role in nuclear transport and cell division.

Neurogen Commences Phase II Clinical Trial in Chronic Insomnia Patients
Neurogen Corporation announced that it has commenced a Phase II clinical trial in chronic insomnia patients with the Company's insomnia agent, NG2-73. The study will measure reduction in time to onset of persistent sleep and sleep maintenance across a range of doses and formulations during two weeks of treatment. NG2-73 selectively modulates receptors of the gamma-aminobutyric acid (GABA) neurotransmitter system and is one of several unpartnered compounds in Neurogen's portfolio.
The Phase II clinical trial is a randomized, double-blind, placebo-controlled, multi-center, parallel group study designed to determine the efficacy and safety of five different dose and formulation profiles of NG2-73 compared to placebo. The primary endpoint will be the time it takes to fall asleep as defined by Latency to Persistent Sleep (LPS). Sleep maintenance will be explored in several secondary endpoints. At least 240 chronic insomniacs, aged up to 64 years, are expected to receive study drug or placebo for 14 days. Polysomnography will be used to measure various sleep parameters.