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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.

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Wednesday, March 2, 2011

New Phase II Data for Generex's AE37 Breast Cancer Vaccine to be Presented at SSO 2011

The 2011 SSO Annual Cancer Symposium runs from March 2nd through March 5th. The SSO Annual Cancer Symposium attracts more than 1,500 surgical oncologists, general surgeons, exhibitors and guests. Attendees come from more than 40 countries.

This year's event is being held at the Henry B. Gonzalez Convention Center & Grand Hyatt Hotel in San Antonio Texas. SSO received a record-breaking 612 abstract submissions for this meeting, and one details vaccine specific immmunologic responses to Generex's AE37 HER2/neu Ii-Key hybrid peptide vaccine. This is the accepted abstract for the event:

"Vaccine-Specific Immmunologic Responses to the Novel Ii-Key Hybrid HER-2/neu Peptide (AE37) Vaccine in a Phase II Clinical Trial"
A. K. Sears, G. T. Clifton, S. A. Perez, K.S. Clive, J. P. Holmes, K. Georgakopoulou, M. Papamichail, S. Ponniah, G. E. Peoples, E. A. Mittendorf
Vaccine-Specific Immunologic Responses to the Novel Ii-Key Hybrid HER-2/neu Peptide (AE37) Vaccine in a Phase II Clinical
Trial A.K. Sears,1* G.T. Clifton,1 S.A. Perez,2 K.S. Clive,1 J.P. Holmes,3 K. Georgakopoulou,2 M. Papamichail,2 S. Ponniah,4 G.E. Peoples,1 E.A. Mittendorf.5 1. Brooke Army Medical Center, San Antonio, TX; 2. Cancer Immunology and Immunotherapy Center Saint Savas Cancer Hospital, Athens, Greece; 3. Naval Medical Center San Diego, San Diego, CA; 4. Uniformed Services University of the Health Sciences, Bethesda, MD; 5. M.D. Anderson Cancer Center, Houston, TX.

Introduction AE37 is the Ii-Key hybrid of the HER-2/neu peptide AE36 (HER-2/neu: 776-790), and is capable of stimulating CD4+helper T-cells with anti-tumor activity. We are currently conducting a prospective, randomized, single-blinded, phase II trial of AE37 + GM-CSF (immunoadjuvant) vs. GMCSF alone for the prevention of breast cancer recurrence. Here we present safety and immunologic data for this clinical trial.

Methods Node positive or high-risk node negative breast cancer patients with any level of HER-2/neu expression (IHC 1+, 2+ or 3+), disease-free after standard treatments were enrolled. Patients were randomized to receive either AE37 + GM-CSF (VG)or GM-CSF alone (CG). Vaccines were given in six monthly intradermal inoculations. Ex vivo (3H-thymidine proliferation assay) and in vivo (delayed type hypersensitivity [DTH]) responses were measured before (R0), mid-series (R3), upon completion (R6), and at six (RC6) and 12 (RC12) months after completion of the vaccine series.

Results We have enrolled 197 patients (VG=86, CG=111). Systemic toxicities were grade ≤ 2 in 96% of VG and 93% of CG; there were no grade 3-5 local toxicities. In the VG, proliferative responses to AE37 and AE36 increased from R0 to all other measured times (AE37: R0=0.98, R3=3.29, R6=3.38, RC6=3.64, RC12=3.68, p <0.001; AE36: R0=0.95, R3=1.92, R6=2.12, RC6=2.18, RC12=1.80; p<0.001) while they did not change in the CG (Figure 1). DTH responses increased in the VG from pre- to postvaccination (AE37: 2.7 vs 30.2 mm, p<0.001; AE36: 2.2 vs 16.3 mm, p<0.001) while there was no change in the CG.

Conclusions In a prospective, randomized, single-blinded, phase II vaccine trial with a GM-CSF only control group, the novel Ii-Key hybrid HER-2/neu AE37 vaccine appears safe and well-tolerated with minimal toxicity. AE37+GM-CSF is effective at generating HER-2/neu-specific immunity as demonstrated by a significant increase in ex vivo and in vivo immune response in vaccinated patients.

Search for poster #60 (P60) here. The PDF for the general program is here.

My Take The post-vaccine DTH levels for AE37 are a very promising hint of the effectiveness of the vaccine. An increase in DTH levels from pre to post vaccination, combined with a decrease in Tregs, are what researchers of a peptide vaccine hope to see. In my previous blog, I relayed information from a new peer review from the United States Military Cancer Institute. The report states that DTH testing has been described as a very reliable method of monitoring immune response to cancer vaccines. The USMCI researchers believe large DTH reaction may correlate with clinical outcome. The post vaccination DTH responses to AE37 have similarly been reported in a Phase I study with HER2/neu early stage breast cancer patients, as well as a Phase I study with HER2/neu early stage prostate cancer patients. I believe a non-expert ad hoc look the combined DTH response is telling us that the immunological response to AE37 is not only potent and as desired, but consitient and reliable.

The response of patients was also measured by reactivity of their T cells to AE37 as measured by their ability to proliferate after being exposed to the peptide. The proliferation assay appears to show consistent and potent responses among the patients. These findings also confirm previous data supplied by AE37's investigators.

This latest abstract once again finds AE37 to be well-tolerated with minimal toxicity. The findings illustrate that there were no grade 3-5 local toxicities, as has been the case in all prior findings. These toxicity findings are in stark contrast to other cancer drugs, and bode well for the peptide vaccine program at the USMCI. Last month, Generex stated in a press release that they are increasing the number of patients enrolled in the study from 190 to 330, and these results show that 197 have been enrolled to date of submission of this abstract. This abstract may have been submitted to SSO a few months ago. Generex is listed as an exhibitor at ASCO's Annual Meeting that will be held between June 4th and 6th. We may see more data presented at this event. AE37 is doing very well.