Tavocept™ (A Novel Chemoprotective Agent).
BioNumerik recently announced results from a second Tavocept clinical trial where a survival increase in patients with adenocarcinoma, the most common type of lung cancer, was observed. Please see “Recent Press Releases” in the “Press Room” section of this site.
Our product candidate in development, Tavocept™ (also known as BNP7787), is an investigational new drug with potential for oncology and non-oncology indications, including potential prevention or reduction of common and serious side effects that can be associated with chemotherapy. Recently, a Phase III clinical trial for Tavocept has been completed in Japan, involving patients with advanced non-small cell lung cancer (NSCLC) who received the chemotherapy drugs paclitaxel and cisplatin as first line therapy every three weeks. The trial results indicate that the number of patients reporting severe sporadic (i.e. intermittent) or cumulative neuropathy was approximately 50% lower in the Tavocept arm of the trial compared to the placebo arm. While this outcome represents a strong trend in favor of Tavocept, the results were not statistically significant. A surprising and medically important observation from the Japanese Phase III NSCLC trial was a longer median survival time for patients receiving Tavocept compared to those receiving placebo, particularly for patients with adenocarcinoma, the most frequently occurring type of lung cancer. The median survival time observed for patients receiving Tavocept was approximately 40 days longer than the median survival time for patients receiving placebo. For patients with adenocarcinoma, the median survival time for patients receiving Tavocept was approximately 138 days longer than the median survival time for patients receiving placebo. Additional observations from the Japanese Phase III NSCLC trial included a statistically significant reduction in cisplatin-induced kidney damage (nephropathy) and a statistically significant reduction in chemotherapy-induced vomiting for patients receiving Tavocept in comparison to those receiving placebo. Additional information about the Japanese Phase III NSCLC trial and about other Tavocept clinical trials is included under the heading “Tavocept Clinical Trial Summary”.
Karenitecin® BNP1350 (Highly Lipophilic Camptothecin). Our product candidate, karenitecin BNP1350, is a fourth generation compound from a novel class of camptothecins we call karenitecins™. Camptothecins are known to have broad anticancer activity, but their use has been limited in part due to common and serious side effects. We have designed karenitecins™ to overcome many of the important limitations of existing camptothecins. Karenitecins™ have demonstrated very high potency and broad activity in preclinical studies against human cancers including prostate, pancreas, lung, breast, colon, ovary and head and neck. Unlike water-soluble camptothecins, karenitecins™ appear to be substantially less sensitive to common tumor mediated (e.g., MDR/MRP/BCRP) drug resistance and camptothecin resistance type mechanisms. In preclinical animal studies, orally administered karenitecin® has demonstrated substantial activity in human cancer xenografts (e.g., brain, prostate, breast, lung, ovarian, melanoma and colon cancers) without toxicity. Phase II clinical trials for karenitecin® have been completed in patients with metastatic melanoma, advanced ovarian cancer, non-small cell lung cancer, and primary brain tumors. Based on the data from these Phase II trials, we have commenced a global Phase III clinical trial of karenitecin® in advanced ovarian cancer patients. The Phase III trial has been designed as a global, randomized, multi-center open label trial to prospectively evaluate the safety and efficacy of karenitecin compared to the chemotherapy drug topotecan (also known as Hycamtin®). Either karenitecin or topotecan will be given intravenously daily for 5 consecutive days repeated every 3 weeks to advanced ovarian cancer patients who have previously been treated with platinum and taxane chemotherapy drugs but have become resistant to the platinum/taxane therapy. We have received written agreement from the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) regarding the clinical trial design and protocol. We believe the safety and efficacy outcomes from the previously completed karenitecin Phase II advanced ovarian cancer trial compare favorably with the historically reported results of approved agents. We also believe that there is a large unmet need for 2nd and 3rd -line therapies that can prevent progression of recurrent or progressive ovarian cancer with reduced risk of cumulative toxicity in patients who have become resistant to platinum/taxane-based chemotherapy. Based on the Phase II outcomes and our pre-clinical data, we are pursuing karenitecin Phase III testing in advanced ovarian cancer patients who have become resistant to platinum/taxane chemotherapy. A Phase I trial with orally administered karenitecin® has also been initiated for patients with solid tumors.
MDAM. MDAM is a patented non-polyglutamylatable antifolate for the treatment of solid tumors, rheumatoid arthritis, psoriasis and asthma. MDAM's chemical structure is related to methotrexate (MTX), which is widely used for cancer, rheumatoid arthritis and immunosuppression. Unlike MTX, MDAM appears to bypass the common forms of antifolate-type drug resistance and in preclinical studies has demonstrated selective cancer cell uptake and superior dose intensity, safety and antitumor activity relative to MTX. Phase I oncology clinical trials for racemic MDAM have been completed.