Tavocept™

Overview

We believe our new drug candidate Tavocept™ has the potential to substantially increase patient survival in the most common type of lung cancer and possibly many other forms of cancer, while concurrently preventing and reducing common chemotherapy-induced side effects. We are utilizing newly identified knowledge about key cancer mechanisms in an effort to change the way that lung cancer and many other cancers are treated in ways we believe could have profound implications for patients. We are developing Tavocept as an investigational new drug with potential for oncology and non-oncology indications.

Ongoing Phase III Tavocept Trial in Primary Adenocarcinoma of the Lung.

In late 2009, we commenced an international multi-center Phase III clinical trial of Tavocept (also known as BNP7787) in patients with primary adenocarcinoma of the lung, the most common type of lung cancer worldwide (the “Tavocept Phase III Adenocarcinoma Trial”). In previous studies, Tavocept has demonstrated the potential to substantially increase overall and one year patient survival while concurrently preventing and reducing the incidence and severity of common chemotherapy side-effects as compared to other currently available treatments for advanced lung cancer. If the results of the Tavocept Phase III Adenocarcinoma Trial are consistent with prior results, Tavocept treatment could result in the largest historically observed increase in patient survival for a first-line agent for the treatment of primary adenocarcinoma of the lung.

The Tavocept Phase III Adenocarcinoma Trial is an international, randomized, multicenter, double-blind, placebo-controlled trial to be conducted at approximately 80 to 100 clinical sites in the United States, Russia, Ukraine and Eastern Europe. The primary objective is to confirm whether Tavocept plus taxane and cisplatin chemotherapy significantly increases overall survival in patients with advanced primary adenocarcinoma of the lung compared to taxane and cisplatin treatment alone. Tavocept’s ability to prevent or mitigate common chemotherapy-induced toxicities will be prospectively evaluated by pre-specified secondary endpoint analyses.

Observations from Previous Tavocept Trials and Meta-analysis of Trial Results.

In two previous smaller randomized, multicenter trials of Tavocept in combination with taxane and cisplatin chemotherapy, we observed large increases in overall survival and one year survival, compared to the control regimens, in patients with newly diagnosed (inoperable) stage IIIB/IV primary adenocarcinoma of the lung. These increases include a 6.7 month (8.9 months in control vs. 15.6 months in Tavocept treated patients) increase in overall survival, with 60% of Tavocept treated patients vs. 36% of control treated patients alive at one year in a U.S. Phase II clinical trial, and a 4.6 month (15 months in placebo vs. 19.6 months in Tavocept treated patients) increase in overall survival, with 73% of Tavocept treated patients vs. 54% of placebo treated patients alive at one year, in a Japanese Phase III trial. These improved survival outcomes were accompanied by medically and statistically significant reductions in side effects commonly observed with the chemotherapy control regimens, including kidney toxicity, anemia, nausea and vomiting, and treatment discontinuation due to chemotherapy-induced neuropathy.

The results of a comprehensive meta-analysis of these two previous randomized Tavocept trials were recently published by the European Journal of Clinical & Medical Oncology (EJCMO). The meta-analysis examined survival outcomes for a combined total of 346 randomized patients participating in the two trials, including 211 randomized patients with primary adenocarcinoma of the lung. All patients received treatment with taxane plus cisplatin chemotherapy. Approximately half of the patients were treated with Tavocept while the other half received chemotherapy alone. The analysis demonstrated a significant overall survival benefit in favor of Tavocept treatment for the combined meta-analysis of the two trials. For the adenocarcinoma subtype, the combined analysis demonstrated a significantly (P=0.009) improved overall survival benefit in favor of Tavocept treatment, representing an approximate 7.7 month increase in overall survival, with 68% of Tavocept treated patients alive at one year vs. 48% of control patients alive at one year (p=0.003). A meta-analysis uses statistical methods to combine results from previous separate but similar studies in order to evaluate the medical outcomes both independently and in a combined manner.

If we observe results in the ongoing Tavocept Phase III Adenocarcinoma Trial that are consistent with results observed for the Tavocept trials discussed in the meta-analysis publication, this would be a substantial potential advance compared to other recently developed first line lung cancer drugs. For example, the cancer drug Avastin^®, also known as bevacizumab, was approved in the United States to treat lung cancer while exhibiting a survival increase of approximately two months when used with a standard chemotherapy treatment regimen. The cancer drug Alimta^®, also known as pemetrexed, when combined with cisplatin treatment in the first line setting, improved overall survival in primary adenocarcinoma patients by about 1.7 months. Recent data for the cancer drug Erbitux^®, also known as cetuximab, with chemotherapy demonstrated a survival increase of about 1.2 months compared to chemotherapy alone in patients with advanced epidermal growth-factor receptor (EGFR)-detectable non-small cell lung cancer. By conducting the Tavocept Phase III Adenocarcinoma Trial, we hope to improve survival in primary adenocarcinoma patients by a significantly greater margin and at the same time prevent and mitigate chemotherapy induced anemia, kidney toxicity, nausea and vomiting, and peripheral nerve damage.

About Lung Cancer and Adenocarcinoma.

Successfully treating and managing lung cancer remains one of the largest unsolved problems in medicine today. Lung cancer is the leading cause of all cancer deaths, and kills more patients annually than breast, prostate, colon, liver, melanoma and kidney cancers combined. Despite some recent improvements, the 5-year overall survival rate for lung cancer is still only 15%.

Adenocarcinoma is a type of cancer that can occur in cells that are in organs such as the lung, colon, prostate and breast. Adenocarcinoma is the most common type of lung cancer, comprising about 40% to 65% of all non-Asians and 60% to 85% of all Asians diagnosed with lung cancer. The incidence of adenocarcinoma of the lung appears to be increasing.

Mechanistic Observations.

As part of our development efforts, we have identified important new mechanisms believed to be associated with survival increases in non-small cell lung cancer patients. BioNumerik has elucidated that Tavocept targets the thioredoxin and glutaredoxin systems, both of which are found to be overexpressed in adenocarcinoma of the lung. It is postulated that Tavocept administration results in interference with key components of the thioredoxin and glutaredoxin systems, which are believed to be major mechanisms involved in the increased survival observed in lung cancer patients receiving Tavocept with chemotherapy.

Potential Additional Tavocept Development Areas.

We believe that Tavocept also has potential applications for other medical conditions including chemotherapy-induced neuropathy, diabetic neuropathy, protection against toxicity from radiation therapy, lymphedema and other potential medical indications.