Generex's Antigen Express: Creating the Next Generation of Cancer Immunotherapy

by: Rich Steffens

Synthetically Designed Immunotherapy Cancer Vaccines

Antigen Express is the fully owned life science subsidiary of Generex Biotechnology (OTCPK:GNBT). Antigen Express is building an impressive pipeline of next generation synthetic therapeutics aimed at a variety of major diseases, including cancer and infectious diseases.
The platform technology of Antigen Express allows for antigen-specific stimulation of a T-helper response to virtually any antigen of known pathogenic potential. Antigen Express is currently evaluating its leading candidate, the novel Ii-key hybrid HER2/neu peptide AE37 vaccine, in a multi-center Phase II trial for patients with breast cancer under a research agreement with the United States Military Cancer Institute.

AE37 is an immunotherapeutic synthetic peptide vaccine designed to prevent the recurrence of a variety of different cancers that express the HER-2/neu peptide. An advantage of Antigen Express' immunotherapy is that it causes none of the toxicities typically associated with classical chemotherapy. While the target of AE37 is the same as that of the Roche's (OTCQX:RHHBY) blockbuster cancer drug 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.

New AE37 Data to be Presented at ASCO 2010

I found evidence that new data for the AE37 vaccine will be presented at the 2010 American Society of Clinical Oncology Annual Meeting to be held in Chicago from June 4-8, 2010. ASCO 2010 abstracts will be available on the company's Annual Meeting website in mid-May, although abstract titles can currently be found on the event itinerary page. The title of an AE37 abstract being presented at ASCO 2010 is Effect of a Novel Ii-key Hybrid HER2/neu Peptide AE37 Vaccine with GM-CSF as Compared to GM-CSF Alone on Levels of Regulatory T-cell Treg Populations. The listed author/speaker is Dr. Guy T Clifton, who has worked extensively on peptide based therapeutic vaccines at the USMCI with Antigen Express collaborator Col. George Peoples.

If Dr. Clifton highlights Phase II data that confirms previously reported Phase I data regarding AE37's effect on regulatory T-cell Tregs, that would be great news for Antigen Express. The Phase I trial for AE37 in breast cancer patients showed that Tregs were reduced in all patients tested pre- to post-vaccination. This smaller Phase I trial also found that DTH responses increased in all patients from pre- to post-vaccination p<0.0001. Boding well in this trial for the vaccine was that there was an inverse relationship between the degree of Treg reduction and the size of DTH response to AE37. The researchers concluded in this trial that the reduced levels of Tregs in vaccinated patients appear to be associated with more robust responses in ex vivo immune assays and in vivo DTH reactions suggesting that the AE37 vaccine may be clinically useful.

This pending update follows the impressive interim results for the AE37 vaccine in its current Phase II trial which were unveiled at the San Antonio Breast Cancer Symposium in December 2009. Two hundred disease-free, high risk, breast cancer patients who had completed standard adjuvant therapy are being enrolled and randomized to receive six monthly inoculations of either the AE37 peptide vaccine or the adjuvant GM-CSF alone to compare their ability to prevent cancer recurrence. This interim analysis followed the first 49 patients in the AE37 group and the first 71 for the control group. At a median follow up of 13 months, there were no (0.0%) recurrences in the AE37 group of patients, 0/49, compared to 7.0%, 5/71, in the control group. You can view the SABCS poster from December here.

AE37 Phase I Results for Prostate Cancer Patients to be Presented at the 25th Annual EAU Congress

This same AE37 peptide vaccine has been evaluated in a Phase I trial with prostate cancer patients. The Phase I results for patients with prostate cancer were first announced at the 2009 ASCO Annual meeting and will be presented at next week's 25th Annual EAU Congress in Barcelona. I found the information online, which is open to public viewing. The studies were conducted at St. Savas Hospital in Athens, Greece. Dr T.K. Karaolides from Saint Savas Cancer Hospital is listed as the speaker at to present these findings during the session "Focal and Systemic Therapies".

The results of study with prostate cancer patients have so far been consistent with those of prior clinical trials of AE37 in patients with breast cancer. Results have shown the AE37 HER2/neu hybrid peptide vaccine has very limited toxicity, with no patients experiencing toxicity over Grade 2. That is a very important advantage since most cancer drugs are hard to tolerate. This listing for the 25th Annual EAU Congress in Barcelona suggests we will soon hear an update for the vaccine with prostate cancer patients.

AE37's Market Potential

Roche and Genentech's (Private:DNA) blockbuster drug, Herceptin, which also zeroes in on cancer that is over-expressing HER-2/neu, can be used only in patients expressing the highest level of HER-2, or about 25 percent of breast cancer patients. In comparison, the AE37 peptide vaccine stimulates the immune system to recognize tumor cells in patients with a lower expression of HER-2, so that 75 percent of breast cancer patients would respond to Antigen's vaccine. Herceptin sales in 2008 were $1.8 billion, and reached approximately $2.5 billion in the first half of 2009.

The potential market for Antigen's vaccine could be even larger since it can be used in more HER-2 patients, and when considering the licensing potential of using AE37 in combination with treatments from other firms. Antigen Express has stated it believes there could be a synergistic response if they use Herceptin with an immunological drug like AE37, but currently the company is more focused on looking at AE37 alone or in combination with other peptides (such as in the AE37 Combo Vaccine).

AE37 Combo Vaccine for Breast and Ovarian Cancer Patients

Beyond the trials previously mentioned, Antigen Express announced in May 2009 that the first patient has received the immunotherapeutic AE37 vaccine as part of a new combination therapy approach for breast and ovarian cancer patients. This vaccine therapy is designed to activate immune cells that can detect and destroy cancer cells. The new Phase I clinical trial is being performed at and fully funded by the Mary Crowley Cancer Research Center in Dallas. It will assess safety and immunological response in patients with either breast and/ or ovarian cancer.

In this new trial, AE37 will be paired with a second HER-2/neu-derived peptide, GP2, designed to stimulate a different portion of the immune system. AE37 stimulates the CD4 cells, considered the immunological generals, while the other peptide stimulates the CD8 cells, which act as the infantry in this unified war against cancer. Enrollment was targeted to be completed this year.

Developed to Prevent Cancer Recurrence

Generex currently has a market cap of just under $120 million, and I believe its wholly owned subsidiary is overlooked and not properly valued alongside other life science developmental firms. If AE37 continues to stimulate such impressive results, then I feel Antigen Express will move towards the top of the list among the companies that are developing therapeutic cancer vaccines. While no cancer vaccine is currently approved by the FDA, most investors are aware that Dendreon Corporation (NASDAQ:DNDN) has a May 1st PDUFA date for Provenge which is designed to treat metastatic prostate cancer.

Since AE37 is being developed to prevent cancer recurrence, I hope Antigen Express' offering will eventually make another drug or vaccine such as Provenge, designed to treat metastatic cancer, one that stays in the back room of the pharmacy. AE37 may lead to longer and healthier lives, while Dendreon's significant advance may extend the last stage of life by a few precious months. They both may prove to be great medical advances to usher in a new era of immunotherapeutic vaccines to revolutionize how cancer is treated.

Small Firm Attempts to Fund a Potential Blockbuster Pipeline

Antigen Express' parent company, Generex Biotechnology, announced last week that it has reached a funding commitment from a private investment partnership, Seaside88, where they will purchase up to 49,455,130 shares of Generex common stock in 25 bi-weekly tranches. More specific terms of this deal can be found on Generex investor relations page under its press releases and SEC filings. As of the latest quarterly filing, Generex recorded 23.6 million in cash and it has been managing a frugal quarterly burn rate of 3 to 4 million, although that figure may increase due to funding requirements of its planned activities. Generex's funding needs may increase for its worldwide Phase III trial, for its novel buccal insulin spray, Oral-lyn, as well as to support the Treatment IND awarded by the FDA for this non-invasive insulin delivery system. With approximately 253 million shares currently outstanding, this figure should increase to over 300 million if the agreement with Seaside88 reaches full commitment.

Moving Forward to Reach its Goals

While Generex has stated that it has begun active discussions with pharmaceutical companies for potential joint ventures and licensing agreements for AE37, it has also visibly strengthened its own financial position. I believe this will enable the company to move forward in realizing its clinical goals, as these discussions may be time consuming and uncertain. As a result of the continued successful study results for AE37, Generex has stated that a Phase III study for breast cancer patients is being planned for later in 2010, as well as a Phase II study for prostate cancer patients. While many hurdles remain before it, I believe Antigen Express will earn a place on the front line in the war against cancer and the company should be noted for its significant market potential.

Disclosure: The author is long GNBT.