NOV-002, the lead compound acts as a chemoprotectant and an immunomodulator, in combination with chemotherapy. In the U.S., Novelos received a "green light" from the FDA for Phase 3 development of NOV-002 for treatment of lung cancer, under a Special Protocol Assessment (SPA) and Fast Track. NOV-002 is approved and marketed in Russia by Pharma BAM under the trade name Glutoxim^®. It has been administered to over 10,000 patients, including clinical studies of 390 patients across many tumor types, demonstrating clinical efficacy and excellent safety data.

Novelos' randomized, open-label, international, pivotal Phase 3 trial is evaluating NOV-002 in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone, in 840 patients with Stage IIIb/IV NSCLC. The trial, with a primary efficacy endpoint of improvement in median overall survival, is being conducted across approximately 12 countries and 100 clinical sites. Novelos commenced the trial in November 2006, and reached target enrollment of 840 patients in March 2008. This pivotal Phase 3 trial is expected to conclude mid-2009.

In the U.S.
The Russian preclinical and clinical data have been sufficiently compelling that the United States Food and Drug Administration (FDA) has accepted them as part of the Investigational New Drug Application (IND) that Novelos has filed for NOV-002.

The U.S.-based Phase 1/2 clinical trial of NOV-002 for non-small cell lung cancer (NSCLC) has been completed, with positive results. Forty-four chemotherapy-naive Stage IIIb/IV NSCLC patients (late-stage lung cancer patients who have not received prior chemotherapy) were randomized to one of three groups for six months of treatment:

Group A: NOV-002, administered intravenously (IV) and intramuscularly, in combination with cytotoxic chemotherapy.

Group B: NOV-002, administered IV and subcutaneously (SC), in combination with cytotoxic chemotherapy.

Group C: Cytotoxic chemotherapy alone was administered to this control group.

Based on the trial protocol, the intent-to-treat analysis of the best overall objective tumor response (i.e. complete or partial tumor shrinkage) showed that eleven out of sixteen (69%) NOV-002 treated patients in Group B demonstrated greater than 50% tumor shrinkage versus only five out of fifteen (33%) in the control group (C). This difference was statistically significant (p=0.044 in a stratified analysis). Six out of thirteen (46%) patients in Group A demonstrated an objective response.

Further, NOV-002 treated patients better tolerated cytotoxic chemotherapy as evidenced by their ability to receive more cycles of chemotherapy compared to the control group (C). 100% of patients in Group B and 85% in Group A were able to complete four cycles of chemotherapy, while only 50% of control group patients (C) were able to do so. These differences were statistically significant (p=0.004). In addition, NOV-002 was well tolerated in this patient population, adding to NOV-002’s already extensive safety database.

In May 2006, Novelos finalized a SPA with the FDA for a single pivotal clinical trial of NOV-002 in combination with first-line chemotherapy, and obtained Fast Track designation in August 2006. The primary endpoint of this trial is improvement in median overall survival, and patient enrollment commenced in November 2006. Target enrollment was reached in March 2008 and trial conclusion is expected mid-2009.

NOV-002 is also being developed to treat chemotherapy-resistant ovarian cancer. A U.S. Phase 2 trial is ongoing at Mass General Hospital and Dana Farber Cancer Institute. As of March 2008, NOV-002 (plus chemotherapy) slowed disease progression in 60% of the patients.

NOV-002 is also being developed to treat early-stage breast cancer. These patients are often treated with chemotherapy to minimize surgical intervention and improve survival. A U.S. Phase 2 neoadjuvant trial is ongoing at Medical University of South Carolina (MUSC) to evaluate the ability of NOV-002 to enhance the effectiveness of such chemotherapy. As of May 2008, the interim efficacy target was achieved earlier than expected, and the trial is moving into stage 2. Furthermore, NOV-002 apparently decreased hematologic toxicities.

In Russia
Numerous clinical studies have been concluded in Russia over the last decade, and NOV-002 was approved as an adjunct to chemotherapy in the Russian Federation in 1998. The Russian approval was obtained by demonstrating clinical efficacy and excellent safety in 340 patients with many types of cancers, including: lung, colorectal, breast, ovarian, pancreatic, etc.

Overall, the studies revealed that NOV-002 could be safely and effectively added to various chemotherapy regimens. The treated patients had a better quality of life and more rapid restoration of hematological and immunological indices. They tolerated the combination therapy better than standard chemotherapy alone, as evidenced by receiving greater number of chemotherapy cycles. Further, in a controlled Russian lung cancer trial, when used in combination with chemotherapy, NOV-002 increased the one year survival rate of patients from 17% to 63% (p < 0.01), a result that represents an 80% improvement over the 35% survival rate seen with the current standard of care in the U.S.

NOV-002 also sensitized previously platinum-resistant ovarian cancer patients to chemotherapy in a Russian-based trial. In combination with NOV-002, 80% of the treated women responded favorably to the same chemotherapy that they previously failed.

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