Biotech Values

[DewDiligence]

Background on the Squalamine program in non-small-cell lung cancer (NSCLC):

With survival data in NSCLC to be presented at ASCO in about six weeks, this is a good time for GENR investors to remind themselves (or to learn for the first time) of the progress to date in this program.

Following are excerpts from two GENR press releases in 2003. (See the links provided for the full releases, after scanning to the ends of the respective SEC documents.)

As described below, the response rate in patients receiving Squalamine plus two chemo drugs was 23%, versus 17% in historical controls where patients received the two chemo drugs by themselves. Of particular note is that the chemo dose used in the Squalamine trial was only one-third the dose used by the patients in the historical controls. Thus, Squalamine not only produced a higher response rate (23% vs 17%), but it also did so using less of the highly-toxic chemo drugs.

http://www.genaera.com/sec_reports/8-K_NSCLC%20Results.pdf
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Genaera Announces Promising Interim Lung Cancer Clinical Trial Results Plymouth Meeting, PA

June 3, 2003 /PRNewswire/ — Genaera Corporation (NASDAQ: GENR) today announced promising interim results for its anti-angiogenic drug, squalamine, in its phase 2b non-small cell lung cancer (NSCLC) clinical trial. The results currently reported are for objective response rate. Additional results from the study are maturing, including survival data. It is anticipated that a presentation of the additional results will be made at the 2004 ASCO meeting.

“These interim clinical results with squalamine in lung cancer, including one complete response, provide continued evidence of its tremendous potential as an anti-angiogenic therapy,” commented Roy C. Levitt, President and CEO of Genaera. “Squalamine is a potent anti-angiogenic molecule with a unique mechanism of action within the activated endothelial cells, including blocking the action of vascular endothelial growth factor (VEGF) and other growth factors. We are pleased that early trends with the weekly dosing regimen of squalamine, together with the carboplatin and paclitaxel cytotoxic chemotherapy, are in fact yielding an improved safety and efficacy profile compared to standard chemotherapy. This is consistent with our prior positive lung cancer and ovarian cancer trials.
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Joan Schiller, MD, Professor of Oncology at the University of Wisconsin, and lead investigator for the trial, commented, “Advanced non-small cell lung cancer remains a disease for which new treatment alternatives are clearly needed. We have promising early results from this lung cancer study, evaluating the ‘metronomic’ dosing strategy with weekly administration of the three medications squalamine, carboplatin, and paclitaxel. The key endpoints of survival duration, and median time to progression, will be maturing, and will continue to be monitored for notable trends. This dosing regimen is an approach that provides early evidence of an improvement in safety and efficacy compared to standard chemotherapy dosing for this serious disease, and prepares the way for further evaluation of squalamine in lung and other cancers.”

The multi-center randomized lung cancer study is evaluating 45 patients receiving weekly dosing of squalamine, combined with weekly chemotherapy of carboplatin and paclitaxel, in patients with Stage IIIB or Stage IV advanced disease. Two patients were withdrawn for intercurrent illness before receiving any study medication. Of the 43 patients receiving study medications, 21 received a squalamine dose of 100 mg/m2, and the 22 received a dose of 200 mg/m2. Objective responses occurred in 23% of the patients (10 of 43; 1 complete and 9 partial responses), with five responses in each of the two dose groups. An objective response is defined as a 50% or greater reduction in tumor size, measured bi-dimensionally by CT Scan, lasting at least 4 weeks, with no new lesions appearing, as rated by the investigators and radiologists.

In comparison, an appropriate historical benchmark objective response rate for this group of patients treated with carboplatin and paclitaxel alone was 17%, as demonstrated in the large Eastern Cooperative Oncology Group (ECOG) study presented at the ASCO meeting in May 2000, and updated upon publication in the January 10, 2002 issue of the New England Journal of Medicine. The ECOG study was done with a once every three weeks carboplatin and paclitaxel dosing, AT THREE TIMES THE DOSE USED WEEKLY IN THE CURRENT STUDY WITH WEEKLY SQUALAMINE [emphasis added]. Also in comparison, the objective response rate was 27% in the prior study using the dosing regimen of every three weeks carboplatin and paclitaxel, with five daily doses of squalamine every three weeks.

Squalamine is the first clinical drug candidate in a class of naturally occurring, pharmacologically active, small molecules known as aminosterols. Squalamine is a potent anti-angiogenic molecule with a unique multi-faceted mechanism of action that blocks the action of a number of angiogenic growth factors, including vascular endothelial growth factor (VEGF). The Company has performed clinical trials evaluating squalamine in the treatment of non-small cell lung cancer, ovarian cancer, and other adult solid tumors. Genaera also is developing squalamine in clinical trials for age related macular degeneration, the leading cause of blindness in the United States.
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http://www.genaera.com/sec_reports/8-K_Squalamine%20Trial.pdf
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Genaera Ends Enrollment in Squalamine Clinical Trial for Lung Cancer

Plymouth Meeting, PA — January 28, 2003 — Genaera Corporation (NASDAQ: GENR) today announced that it has ended further enrollment in its ongoing Phase 2b non-small cell lung cancer clinical trial for squalamine, its anti-angiogenic agent. Forty patients have currently been enrolled in the study, which is designed to enroll up to 90 patients. “We have decided to end enrollment in this clinical trial in order to further conserve capital for our other development programs for squalamine and LOMUCINTM,” commented Roy C. Levitt, President and Chief Executive Officer. “We do not believe that the additional patient data and expense associated with the larger study for this particular trial design will add significantly to our business development opportunities for squalamine.

We have decided to take this step at the planned interim administrative review after 40 patients were enrolled, which makes this study approximately the same size as our previous phase 2 trial for nonsmall cell lung cancer. There are no safety concerns with the trial thus far and clinical data are being collected from a significant number of patients who remain on therapy. Response rate to therapy and safety data from this study should be complete and made available in mid-year 2003, while survival data should be available in mid-year 2004.
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