Welcome to Pipeline Review

Generex Biotechnology, and their wholly owned subsidiary Antigen Express, are developing promising new drugs to treat diabetes, as well as synthetic peptide vaccines targeting HER2/neu cancer and pandemic flu. The flagship product for Generex is Oral-lyn buccal insulin. Antigen Express' leading vaccine is the AE37 HER2/neu synthetic peptide vaccine to prevent breast cancer recurrence. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I am a layman and a shareholder in this company. The left side of Pipeline Review holds blogs regarding Generex and Antigen Express, while the right side offers items of due diligence mixed with my analysis which may be of interest to others seeking to learn about Generex's pipeline. If the left side only shows the latest blog, click on the word home to view them all.

Search This Blog

Saturday, June 21, 2008

The United States Military Cancer Institute: Armed with Antigens in the War Against Breast Cancer

The United States Military Cancer Institute has been investigating peptide based vaccines for therapuetic value in the war against breast cancer. Previous attempts at developing peptide vaccines for breast cancer had been largely disappointing. However, those vaccines were designed to treat metastatic disease. In contrast, the USMCI researchers, based at Walter Reed Army Medical Center, have been investigating novel peptide vaccines as a preventive therapy for patients who have been treated for breast cancer and have a high risk of recurrence. In particular, the researchers have focused their efforts on two impressive peptide vaccines.

E75 Peptide Vaccine

E75 is a novel anti-HER2 breast cancer vaccine. The E75 protein is a rich target for therapy since it is specifically recognized by immune cells. The HER2/neu protein is an oncogene highly expressed in certain adenomas, including 20%-40% of breast cancers and some forms of colon cancer. E75 has been licensed to Apthera, a private company, which also renamed the vaccine candidate as NeuVax.

In April, Apthera and the USMCI announced results from analysis of a randomized safety and efficacy clinical trial studying NeuVax (E75) in the adjuvant treatment of early-stage (node-positive and high risk node-negative), HER2-positive breast cancer. The data showed that patients with low-expressing HER2 tumors experienced decreased breast cancer recurrence and no mortality to-date following treatment. Taken together these findings may be significant for the greater than 50 percent of breast cancer patients whose tumors fall into the HER2 low-expressing category and who are not typically eligible for Herceptin treatment.

The difficulties faced in further development of E75 is that it's effectiveness has been seen to wane after a few months. A Phase III trial is being planned as well as other studies investigating the need for a booster shot or higher doses of the peptide and the adjuvant GM-CSF. Unpublished data from researchers at the USMCI also appear to show the potential linking of E75 to a li-Key/HER2/neu MHC class II peptide which brings us to the subject of the other promising therpauetic vaccine in the USMCI's arsenal.

AE37 Vaccine

Like E75, AE37 is being tested under the direction of Colonel George Peoples, M.D., at Brooke Army Medical Center. The AE37 study is a collaboration among Antigen Express, USMCI, the Uniformed Services University of the Health Sciences (USU) and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). Antigen Express entered into a Clinical Trial Agreement with HJF to enable work with Peoples, USMCI and USU, with the goal of advancing the company's HER-2/neu vaccine efforts for breast cancer.

Specifically, AE37 is a li-Key/HER2/neu MHC class II peptide discovered and patented by Dr. Robert Humphreys and Dr. Minzhen Xu of Worcester's Antigen Express. Antigen Express is a wholly owned subsidiary of Generex (GNBT) Biotechnology. The immunotherapeutic agent being developed by Antigen Express is a peptide derived from a tumor-associated protein that has been modified to enhance the stimulation of CD4+ T helper cells. The target protein is encoded by the HER-2/neu oncogene, which has been found to be over-expressed in tumors from a variety of cancers, including breast, ovarian, prostate, lung, colon, stomach and pancreatic cancers. Antigen-specific stimulation of T helper cells, which occurs after immunization with AE37, has been shown in prior studies to be critical for the immune system to mount an effective anti-tumor response.

Earlier this month at ASCO, Generex and the USMCI presented final Phase I data for AE37 in breast cancer. The vaccine was found to be safe and well tolerated in breast cancer patients. There were no patients that experienced toxicity over grade two. The remarkable aspect of this first human experience with Antigen Express's li-Key/HER2/neu MHC class II moiety is that the immunological response was so robust to AE37 that the investigators continued to lower the dose of the adjuvant GM-CSF. Eventually, they removed the adjuvant from the vaccine. This is remarkable because the investigators at the USMCI concluded that "AE37 is the first peptide vaccine derived from a tumor-associated antigen that elicits a robust immunologic response in cancer patients without the use of an immunoadjuvant".

While the target of AE37 is the same as that of Herceptin, the activity of AE37 relies on its ability to stimulate a patient's own immune system to recognize the cancer target rather than by interacting with the target directly. The advantage of this is that the immune system, once activated, is capable of detecting lower levels of the target protein than is Herceptin and that the anti-tumor activity lasts long after termination of AE37 treatment.

USMCI Future Plans

The USMCI and Apthera are planning E75's Phase III trial for later this year. In early 2007, Generex and the USMCI commenced patient dosing in AE37's Phase II trial. The AE37 trial is a randomized, multi-center study among patients who have completed standard therapy for node-positive or high-risk node-negative breast cancer expressing at least low levels of the HER-2/neu oncogene. These patients are at an increased risk for recurrence. The endpoint for the study will be a 50 percent reduction in rate of relapse of the disease at the two-year point. The AE37 Phase II was designed by the USMCI as a large scale efficacy study to take advantage of changing paradigms (not yet adopted) for the study of therapeutic cancer vaccines, which proposes a two-phase rather than a three-phase clinical investigation strategy.

In a recent interview, Col. Peoples discussed the development of the E75 vaccine. "This is a very basic vaccine and much less sophisticated than other cancer vaccines that are in development," he said. "Actually, most people felt that a simple vaccine like this could not work—that we would need multiple peptides to make a 'super vaccine.'" Compared to E75, Dr. Peoples commented, "AE37 is also safe and effective, and causes an even more dramatic immune system response."

In the war against breast cancer, novel peptide based vaccines are being developed at the United States Military Cancer Institute that pose a needed threat to cancer relapse. These vaccines will be more applicable to the whole spectrum of HER2 as compared to Herceptin. The peptide vaccines will be easier to manufacture and cost much less. The USMCI is also designing studies looking at the peptide vaccines used in conjunction with Hercpetin. In all wars, it is a unified front that brings the best chance of victory. Are Genentech and larger oncology players like GlaxoSmithKline (GSK) paying attention?