AE 37 / Generex, Shenzhen BioScien - LARVOL DELTA

AE37 HER2-targeted vaccine in the prevention of breast cancer recurrence: A mini narrative review of current evidence. (PubMed, Medicine (Baltimore)) - "While the AE37 HER2-targeted vaccine demonstrates a promising safety profile and potential efficacy in specific breast cancer subgroups, an understanding requires addressing identified limitations and advancing research in nuanced directions. This paper provides a foundation for navigating the complex landscape of breast cancer immunotherapy with the AE37 vaccine."

Journal • Review • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Subgroup efficacy evaluation of the AE37 HER2 vaccine in breast cancer patients in the adjuvant setting. (ASCO 2017) - P2; "The AE37 vaccine is safe and well tolerated and has statistically significant efficacy in stage IIB/III pts with HER2 LE and in TNBC pts. This justifies further evaluation in a phase III study enrolling stage IIb/III pts not eligible for trastuzumab treatment and the very high risk TNBC group."

Clinical • Biosimilar • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Triple Negative Breast Cancer

NSABP FB-14: Establishing the Recommended Biological Dose for AE37 Peptide Vaccine in Combination With Pembrolizumab That Will Enhance the Tumor-specific Immune Response and Demonstrate Efficacy in Patients With Advanced Triple-negative Breast Cancer (clinicaltrials.gov) - P2; N=29; Active, not recruiting; Sponsor: NuGenerex Immuno-Oncology; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

AE37: a HER2-targeted vaccine for the prevention of breast cancer recurrence. (PubMed, Expert Opin Investig Drugs) - "Over-expression has been correlated with the poorest overall survival and has been the target of successful therapies such as trastuzumab. Expert Opinion: Future trials utilizing the AE37 vaccine to treat other HER2-expressing malignancies are likely to see similar success, and this will be enhanced by combination immunotherapy. Ii-Key modification of other peptides of interest across oncology and virology could yield impressive results over the longer term."

IO biomarker • Journal • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • CSF2 • HER-2

Exploring Essential Issues for Improving Therapeutic Cancer Vaccine Trial Design. (PubMed, Cancers (Basel)) - "Although scientists working on cancer immunotherapy feel that this is an essential breakthrough for the field, they still expect that new vaccine regimens will yield better clinical benefits compared to the four months prolonged median overall survival (OS) Sipuleucel-T demonstrated in the IMPACT phase III clinical trial...Thus, rigorous re-evaluation of these trials is urgently required in order to redefine aspects and optimize the benefits offered by therapeutic cancer vaccines. The scope of this review is to provide to the reader our thoughts on the key challenges in maximizing the therapeutic potentials of cancer vaccines, with a special focus on issues that touch upon clinical trial design."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Generex Subsidiary NuGenerex Immuno-Oncology Announces Publication of a Review Article on Cancer Vaccines Highlighting AE37 (Ii-Key-HER2) Immunotherapeutic Vaccine (GlobeNewswire) - P2b, N=29; NSABP FB-14 (NCT04024800); Sponsor: Antigen Express, Inc; "The paper clearly describes why the Phase IIb clinical trial of AE37 in breast cancer demonstrated a statistically significant clinical benefit for certain subgroups of patients in the trial (advanced stage disease with low HER2 or triple negative breast cancer) while failing to meet the primary endpoint in the entire intent-to-treat (ITT) study population. The introduction of Herceptin (trastuzumab) as the standard of care during the long-term follow-up of the trial skewed the results such that the benefit of AE37 could not be detected in the statistical analysis. However, when looking at patients in subgroups that did not receive Herceptin, the positive benefits of AE37 on survival become apparent...'The paper also validates our future plans for AE37 clinical development, as we plan to initiate a trial in bladder cancer'..."

New trial • P2b data • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Triple Negative Breast Cancer

Preliminary results for the phase 1 trial of a dual HER2 peptide cancer vaccine in breast and ovarian cancer patients (SABCS-2013) - Abstract #P4-13-02; P1, N=28; "No dose-limiting toxicity was observed. For the 14 patients who completed the VS, the median age was 51(35-83). Breast tumor size was 3.3±1.1cm and ovarian tumor size was 10.0±2.3cm. Compared to GP2 LR at R1 (15.5±4.1mm), LR increased at R2 (31.7±5.9mm), R3 (42.9±7.4mm), R4 (35.3±7.3mm), R5 (45.0±9.9mm), and R6 (25.9±6.7mm, p=0.17). Compared to the AE37 LR at R1 (18.5±3.8mm), LR increased at R2 (37.3±6.7mm), R3 (36.4±4.6mm), R4 (42.2±5.9mm), R5 (46.0±8.9mm), and R6 (36.2±6.6mm)."

P1 data • Breast Cancer • Oncology • Ovarian Cancer

Generex Biotechnology Announces Corporate Update and Investor Conference Call: NuGenerex Immuno-Oncology Today Friday July 10, 2020 at 4:15 PM (GlobeNewswire) - "Generex Biotechnology Corporation…announced call-in details for today’s investor conference call on Friday July 10th 2020 at 4:15 PM Eastern time…Agenda: Published study results from AE37 Phase II breast cancer trial with 10-year follow-up; Update on the Phase II trial of AE37 with Pembrolizumab (Keytruda®) for the Treatment of Triple Negative Breast Cancer."

P2 data • Breast Cancer • Oncology • Triple Negative Breast Cancer

Invariant chain-peptide fusion vaccine using her-2/neu (Methods Mol Biol) - "HER-2(776-790) (or AE36), which is derived from the intracellular domain of HER-2/neu, has been intensively used as an Ii-key/HER-2(776-790) (or AE37) fusion (hybrid) vaccine in clinical trials. This chapter describes procedures for the synthesis, reconstitution, sterility testing, and storage of both AE36 and AE37 for their use in clinical trials."

Review • Oncology

Investor Presentation (Generex) - AE 37 / Generex; Anticipated completion of P2 trial for breast cancer in 2012; Anticipated initiation of P3 trial for breast cancer in Q1 2012

Anticipated P2 trial completion • Anticipated P3 trial initiation • Oncology

Generex announces publication of biomarker studies related to the Antigen Express novel immunotherapeutic AE37 in prostate cancer patients (Generex Press Release) - P1, N=29; "Generex...announced publication of studies examining potential biomarkers associated with overall survival in prostate cancer patients treated with its immunotherapeutic agent AE37....A variety of immune related markers were examined for correlation with overall survival. Of particular interest were the findings that AE37-induced immune responses appeared to be stronger in patients with low levels of HER2 expression as well as in patients with earlier stages of disease."

Biomarker • Oncology • Prostate Cancer

Generex announces publication of abstract at ASCO 2012 showing potential of Antigen Express AE37 immunotherapeutic cancer vaccine technology in prostate cancer (ASCO 2012, PRNewswire) - P1, N=8; Generex published an abstract demonstrating a more broad & robust immunological response in AE37 treated pts with prostate cancer; Pts who received AE37 vaccine had an augmented HER2 immunological response & a stronger response to PSA

P1 data • Oncology

Generex announces publication of abstract at ASCO 2012 showing potential of Antigen Express AE37 immunotherapeutic cancer vaccine technology in prostate cancer (ASCO 2012, PRNewswire) - P1, N=8; Generex published an abstract demonstrating a more broad & robust immunological response in AE37 treated pts with prostate cancer; Pts who received AE37 vaccine had an augmented HER2 immunological response & a stronger response to PSA

P1 data • Oncology

Generex subsidiary Antigen Express announces publication of review showcasing its proprietary therapeutic vaccine technology in the journal Vaccine (Market Watch) - Generex Biotechnology announced that a review of the Antigen Express proprietary platform technology for generation of immunotherapeutic vaccines has been published in the peer-reviewed journal Vaccine; The article reviews preclinical & clinical studies from the last ten years to the present time demonstrating the importance of generating specific CD4+ T-cell activation in the immunotherapy of cancer

Publication announcement • Oncology

Antigen Express' AE37 cancer vaccine featured in scientific American article coincides with breast cancer awareness month in October (Market Watch) - Antigen Express announced that its lead drug candidate AE37 is featured in the October 2011 issue of Scientific American; AE37 is also described as a peptide-based vaccine that uses bits of the HER-2/neu protein that are small in size, inexpensive to synthesize & very easy to manipulate

Review • Oncology

Correlation of HER2/neu antibody response to clinical response in a phase II trial of the AE37+GM-CSF HER2 peptide vaccine (SITC 2014) - P2, N=298; "HER2 AR was less in NR versus R at R0 (3659mfi ± 70 vs 4799mfi ± 170, p < 0.01) and R6 (3832mfi ± 82 vs 4832mfi ± 30, p < 0.01). ΔR6 (R6-R0), AR change post-PVS, was increased in NR compared to R patients (174mfi ± 36 vs 33mfi ± 70, p < 0.07). AR was greater in HER2 OE compared to nOE (R0: 4991mfi ± 169 vs 3563mfi ± 70, R6: 4721mfi ± 127 vs 3888mfi ± 84, p < 0.01)."

P2 data • Breast Cancer • Oncology

CD4+ T-cell activation for immunotherapy of malignancies using Ii-Key/MHC class II epitope hybrid vaccines (Vaccine) - The Ii-Key hybrid AE37, generated by linking LRMK to the known HER2 MHC class II epitope HER2 (aa 776-790), has been shown to generate robust, long lasting HER2-specific immune responses both in pts with breast & prostate cancer; Interim data from a P2 study of AE37 in breast cancer pts suggest a possible improvement in clinical outcome

Review • Oncology

Booster inoculations of the AE37 peptide vaccine enhance immunological responses in a phase II study (ASCO 2013) - Presentation time: Monday, Jun 3, 8:00 AM - 11:45 AM; Abstract #3095; P2, N=25; NCT00524277; "Mean dermal reactions (orthogonal mean in mm) in vaccinated patients was 25.9±3.13 at completion of the PVS (R6) and increased to 35.47±4.35 at BRC24 (p=0.01). VG patients increased their proliferation response (stimulation index, SI) to AE36 from 0.97±0.046 at baseline (R0) before vaccination to 2.27±0.57 at R6 (p=0.0003) which was maintained until BRC24 (SI 2.21±0,33, p<0.0001)."

P2 data • Breast Cancer • Oncology

Final pre-specified analysis of the phase II trial of the AE37+GM-CSF vaccine in high risk breast cancer patients to prevent recurrence (ASCO 2015) - Presentation time: Saturday, May 30; 8:00 AM - 11:30 AM; Abstract #622; P2; N=301; NCT00524277; "Five-year DFS rates were not different with 82% (VG) vs 79.9% (CG), HR = 0.96, p = 0.9. There were trends in several subgroups. In HER2 1-2+ pts (77 VG vs 80 CG), 5 yr DFS was 79% (VG) vs 75% (CG), HR 0.76, p = 0.48. In ER/PR- pts (59 VG vs 56 CG), 5 yr DFS was 83% (VG) vs 77% (CG), HR 0.67, p = 0.36. In TNBC pts (25 VG vs 26 CG), 5 yr DFS was 67% (VG) vs 62% (CG), HR 0.65, p = 0.42."

P2 data • Breast Cancer • Oncology

Antigen drug valued at $300M (Worcester Business Journal) - Antigen Express's AE37 is expected to begin a P3 clinical trial treating breast cancer; Antigen Express has also received preliminary notice of allowance from the U.S. Patent Office to extend protections of AE37 until 2028

Anticipated P3 trial initiation • Patent allowance • Oncology

Breast cancer vaccine reduces cancer recurrence in women: Interim results from phase 2 clinical trial trend toward AE37 vaccine benefit; Results presented at SABCS (PRNewswire) - P2, N=250; Updated data presented at SABCS demonstrate that DFS in the low HER2 expressing pts was 88.6% in the treated group (n=53) vs. 71.9% in the control arm (n=78) at a median follow-up of 22 months; Final phase 2 results expected in 2012

Anticipated P2 data • Interim P2 data • Breast Cancer • Oncology

Early efficacy analysis of the AE37 vaccine in patients with HER2 low-expressing and triple-negative breast cancer (ASCO-BC 2012) - P2, N=254; After a median follow-up of 22.3 months, the disease-free survival (DFS) rate in the vaccine group (VG) is 90.3% vs. 81.1% in the control group (CG) (p=0.46), a 49% risk reduction; Evaluating patients with low HER2 expression (IHC 1+ or 2+), there are 53 VG pts & 77 CG pts; The DFS rate in the VG of low HER2 expressers is 89.8% vs. 68.2% in the CG (p=0.12), a 68% risk reduction

P2 data • Breast Cancer • Oncology

Risk factors for development of delayed urticarial reactions in the phase II trial of HER2 peptide vaccines plus GM-CSF versus GM-CSF alone in high-risk breast cancer patients to prevent recurrence (ASCO 2013) - Presentation time: Monday, Jun 3, 8:00 AM - 11:45 AM; Abstract #3097; P2, N=24; NCT00524277; "DTH response is similar in vDUR pts v. noDUR VG pts (R0- p = 0.34; R6- p=0.40). cDUR pts had a greater DTH response v. CG noDUR pts at R6 (13.2 v 4.7 mm, p=0.01). LRs are greater in DUR pts compared to noDUR pts after the second vaccination (R2 – 66.2 v 48.2 mm, p=0.02). LR for DUR pts decrease and are less than noDUR at R6 (45.4 v 57.4 mm, p=0.09). Relative risk for developing DUR for LR > 100 mm at R2 is 3.49 (1.58-7.68, 95% CI [p=0.004]). At 29.9 months median follow-up, there have been no recurrences in VG and CG DUR v. 75.9% DFS for noDUR (p=0.05)."

P2 data • Breast Cancer • Oncology

Generex announces completion of enrollment of Antigen Express phase II AE37 breast cancer vaccine trial (Generex Press Release) - P2, N=600; NCT00524277; "Generex Biotechnology Corporation...announced completion of enrollment of the Antigen Express, Inc. ...AE37 breast cancer immunotherapy trial....While a pre-planned primary efficacy analysis is underway, completion of enrollment sets the time-point for the end-of-trial analysis, scheduled to be conducted one year's time."

Anticipated P2 data • Enrollment closed • Breast Cancer • Oncology

Generex Biotechnology: Antigen Express Scientific Advisory Board Conference Call (Generex) - "Disease Free-Survival: Log Rank: p=.366; Median F/U: 24 mo"; Disease Free-Survival: HER2 low-expressors: Log Rank: p=.134; Median F/U: 24 mo"

P2 data • Breast Cancer • Oncology