Drug Pipeline Series: Phase I, Nov 6 - Nov 13, 2006

Neurogen Announces Phase I Clinical Trial for Proprietary Obesity Drug
Neurogen Corporation announced that it has commenced Phase I human testing of the Company's leading drug candidate for treatment of obesity. The compound, NGD-4715, works as an antagonist at the melanin concentrating hormone receptor-1 (MCH1). NGD-4715 and other compounds in the Company's obesity program are wholly-owned by Neurogen.

The Phase I clinical trial is a randomized, double-blind, placebo-controlled evaluation in healthy overweight and obese subjects of the safety, pharmacokinetics, and pharmacodynamics of single rising oral doses of NGD-4715. The study has a planned total enrollment of up to 84 male and female subjects. This single center study will be conducted in the U.S. and standard safety assessments will be made.


Neose Technologies Announces Initiation of Phase I Trial of GlycoPEG-GCSF
Neose Technologies, Inc. announced that its partner, BioGeneriX AG, a company of the ratiopharm Group, has begun dosing healthy volunteers in a Phase I clinical trial of GlycoPEG-GCSF, a long-acting, GlycoPEGylated™ granulocyte colony stimulating factor for the treatment of neutropenia. The trial, which is being conducted in Western Europe, will evaluate the safety, pharmacokinetics and pharmacodynamics of GlycoPEG-GCSF versus Neulasta® in approximately 60 healthy volunteers. The Phase I trial is designed as a single-blind, randomized, ascending-dose study that will evaluate subcutaneous administration of GlycoPEG-GCSF.

G-CSF is prescribed to stimulate the production of neutrophils, and is approved for sale in major markets around the world for the treatment of neutropenia associated with myelosuppressive chemotherapy. Worldwide sales in the G-CSF category were approximately $4 billion in 2005.

Neutropenia is a severe reduction in the number of neutrophils (mature white blood cells) in the circulating blood, commonly associated with cancer chemotherapy. Patients with neutropenia are at increased risk of developing serious infection. If not treated promptly, neutropenia can be life-threatening.


Interferon Alpha Enters Phase Ia Clinical Trial
Maxygen, Inc. announced that Roche has initiated a Phase Ia clinical trial in New Zealand to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Maxy-alpha, a next-generation interferon alpha for the treatment of hepatitis C virus infection.

The Phase Ia clinical trial is a double-blind, dose-escalation, controlled study of a single sub-cutaneous administration of Maxy-alpha in healthy volunteers with both placebo and PEGASYS® (peginterferon alfa-2a (40KD)) control groups. Maxy-alpha, also known as R7025, Roche's internal designation for the molecule, is a novel PEGylated interferon alpha variant created through the use of Maxygen's proprietary MolecularBreeding™ directed molecular evolution technologies. Maxy-alpha has been designed to have more anti-viral activity against the hepatitis C virus and be more effective in stimulating immune responses to help combat the infection.

Phase 1 Clinical Trial Results for QUADRAMET® Combination Study in High-Risk Prostate Cancer Patients
Cytogen Corporation announced results from a Phase 1 clinical trial of QUADRAMET® (samarium Sm-153 lexidronam injection) in combination with hormonal therapy and external beam radiation therapy in high-risk, clinically non-metastatic prostate cancer patients. Data from the study indicate that the combination regimen was well tolerated with preliminary anti-tumor activity observed as evidenced by prostate specific antigen or PSA responses.

Twenty patients with newly diagnosed high risk (PSA>20 ng/mL and Gleason score greater than or equal to 7; or greater than or equal to T2 and Gleason score greater than or equal to 8) clinically non-metastatic (known as M0) prostate cancer were treated with a regimen consisting of one month of hormonal therapy followed by a single administration of QUADRAMET followed by four more months of hormonal therapy in combination with external beam radiation therapy (RT). RT was administered as 46.8 Gy to the pelvic region and 23.4 Gy to the prostate (total dose of 70.2 Gy). QUADRAMET was administered in escalation doses of 0.25 mCi/kg (4 patients), 0.5 mCi/kg (4 patients), 0.75 mCi/kg (6 patients) and 1.0 mCi/kg (6 patients). The primary endpoint of the study was assessment of the incidence of Grade 3 (or higher) toxicity following all therapy.


ArQule Announces Data from Phase 1B Trial with ARQ 501 and Docetaxel
ArQule, Inc. announced data from a Phase 1b combination therapy trial with ARQ 501 and docetaxel that support previously announced findings demonstrating clinical tolerability and promising signs of anti-tumor activity in cancer patients with a range of advanced solid tumors who had failed prior treatments with a range of anti-cancer therapies.

These data were presented as a poster at the 18th EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics in Prague (A Phase 1b Trial of ARQ 501, a Checkpoint Pathway Activator, in Combination with Docetaxel in Patients with Advanced Solid Tumors - Poster Number 387). Initial data from this trial were disclosed in a June 2006 publication in the 2006 Proceedings of the American Society of Clinical Oncology (ASCO).


ZymoGenetics and Serono Report Detailed Positive Results From Atacicept Phase 1b Clinical Trial in Patients With Lupus
ZymoGenetics, Inc. and Serono presented positive results at the American College of Rheumatology (ACR) annual meeting from a Phase 1b study in systemic lupus erythematosus (SLE) patients treated with atacicept. The results showed that atacicept was well tolerated across all dose levels and schedules in the study. In addition, atacicept therapy was associated with clear biologic activity, as shown by dose-dependent reductions in several biologic markers, consistent with atacicept's proposed mechanism of action.

The primary objective of the dose-escalating Phase 1b clinical trial, which included 49 patients with SLE in 6 cohorts, was to determine the safety and tolerability of atacicept administered subcutaneously. Secondary objectives included examining the effects of various dose and schedule regimens on markers of biologic activity and disease activity.

ZymoGenetics and Serono are in dialogue with the FDA regarding the SLE Phase 2 clinical development program. The companies are planning to initiate the trial in SLE in mid-2007.

AMPLIMED PRESENTS DATA ON IMEXON IN ADVANCED SOLID TUMORS
AmpliMed reported final results from the Phase I trial of its lead drug candidate, Amplimexon (imexon for injection), in patients with advanced solid tumors. The results were presented the International Conference on Molecular Targets and Cancer Therapeutics.
Data from the Phase I study show that Amplimexon is well-tolerated and provides objective evidence of antitumor activity. The multicenter study involved 49 patients with a variety of solid tumors including melanoma, pancreatic, ovarian, colon, uterine, lung and prostate cancers. Patients were administered a range of doses from 20 to 1,000 mg/m2 of Amplimexon as a 30-minute infusion daily for five days every two weeks. The maximum tolerated dose (MTD) of this schedule of administration was determined to be 875 mg/m2/day. Pharmacokinetic studies revealed peak blood levels of imexon at the MTD that were well in excess of those shown to have antitumor effects in preclinical testing. Pharmacodynamic studies showed a correlation between a decrease in the plasma levels of cystine, a thiol-containing compound, and blood levels of imexon, providing additional support for the theory that imexon exerts its effects in part by binding thiols in cells and causing increased intracellular antioxidant levels.
Imexon is a cyanoaziridine compound that showed evidence of activity in limited studies in lung cancer, melanoma and breast cancer that were documented in publications in the 1980s. The potential of imexon as a cancer drug was never fully explored, until 1994 when AmpliMed initiated a program to decipher Amplimexon's mechanism of action. This led to the start in 2003 of a Phase I clinical study of the drug as a standalone therapy in late-stage cancer patients. Further preclinical research revealed that the combined use of Amplimexon and certain other chemotherapeutics resulted in a significant increase in efficacy compared with either drug alone. These findings are now being translated into a series of Phase I/II clinical studies of combination therapy in patients with various types of cancer.


First Patient Enrolled in OXiGENE's Phase Ib Trial of its Lead Vascular Disrupting Agent, CA4P, in Combination with an Antiangiogenic Agent, Bevacizumab (Avastin) for the Treatment of Advanced Cancer
OXiGENE, Inc. announced that the first patient has been enrolled and dosed in its Phase Ib clinical trial in advanced solid tumors, which combines its lead Vascular Disrupting Agent (VDA), CA4P, with an antiangiogenic agent, bevacizumab (Avastin). In a recent Science (Shaked, et al, 2006) publication, the combination of a VDA with an antiangiogenic agent was described as offering a powerful and highly targeted regimen for suppressing tumor growth. Dr. Richard Chin, President and CEO of OXiGENE, stated, "We are very excited to begin enrollment in this important trial. We believe that the combination of CA4P and Avastin has the potential to bring significant benefit to patients. This patient enrollment also highlights our renewed focus on executing our programs rapidly and on schedule." OXiGENE believes that this dose escalation trial is the first step toward fully elucidating the efficacy and safety profiles of combining VDAs and antiangiogenic agents in patients.


InSite Vision Announces Initiation of a Phase 1 Safety Trial on AzaSite Plus™InSite Vision Incorporated announced that a Phase 1 (safety) clinical study for AzaSite Plus (ISV-502), a combination antibiotic/corticosteroid, has been initiated. AzaSite Plus, the next product in the AzaSite product franchise, combines azithromycin and dexamethasone in DuraSite which is InSite Vision's drug delivery system for topical ophthalmic indications.

AzaSite Plus provides the broad bacteria coverage of InSite Vision's AzaSite product (for which an NDA has been filed), featuring reduced dosing and drug safety, while the addition of dexamethasone provides a proven steroid for the treatment of ocular inflammation. The product would be indicated for ocular treatment where inflammation and bacterial infection are present, typically represented in conditions such as blepharitis. The Phase 1 clinical study is intended to evaluate both the safety and tolerability of the AzaSite Plus formulation in normal volunteers.