Clinical Development of Ii-Key Immunotherapeutic Vaccines
Hundreds of People Have Been Safely Vaccinated with Ii-Key Peptide Vaccines
AE37 – Ii-Key-HER2 Immunotherapeutic Vaccine
The company’s most advanced immunotherapeutic product is AE37, an Ii-Key-HER2 vaccine that contains the HER2/neu antigenic peptide linked to the Ii-Key to enhance immune stimulation against HER2, which is expressed in numerous cancers.
Phase I Breast Cancer
In Phase I studies, AE37 has demonstrated a clean safety profile and generated T-cell immune responses in patients with breast cancer.
Phase II Breast Cancer
The final results of the Phase IIb clinical trial of AE37 vaccine for the prevention of recurrence of breast cancer have been published in the peer-reviewed journal, Breast Cancer Research & Treatment. In the AE37 arm of this trial, patients with advanced stage, HER2 under-expression, and TNBC showed benefit from AE37 vaccination, and those with both advanced stage and HER2 under expression have a significant clinical benefit to AE37 vaccination, demonstrating improved disease-free survival for up to ten years of follow-up. Brown et al. Breast Cancer Research & Treatment; 8 April 2020
Phase II Triple Negative Breast Cancer: AE37 +/- pembrolizumab (Merck’s Keytruda®)
Based on the promising results from this trial, NuGenerex has entered into a collaborative agreement with Merck Sharpe & Dohme Corp. (Merck) and the National Surgical Adjuvant Breast and Bowel Program (NSABP) to conduct a Phase II trial to evaluate the safety and efficacy of AE37 in combination KEYTRUDA (pembrolizumab) in patients with metastatic triple‐negative breast cancer. The trial is ongoing.
Phase I/IIa Prostate
We conducted a phase I/IIa trial of AE37 with recombinant granulocyte macrophage colony-stimulating factor as adjuvant in patients with HER-2/neu+ prostate cancer. The primary end points of the study were to evaluate toxicity and monitor patients’ immune responses to the vaccine. The trial demonstrated safety and strong immunological response (both CD4+ and CD8+ T-cell responses) to AE37 in prostate cancer patients, with T-Cell memory responses lasting for 3 years. The investigators concluded that AE37 vaccine is safe and can induce HER-2/neu–specific cellular immune responses in patients with castrate-sensitive and castrate-resistant prostate cancer, thus emphasizing the potential of AE37 to target HER-2/neu for the immunotherapy of prostate cancer. Clin Cancer Res; 16(13); 3495–506.
AE37 Immunotherapeutic Vaccination for Prostate Cancer:
Phase I/IIa Three Year Immunogenicity Follow-up
*After 3 years, the AE37 vaccinated patients were challenged with AE36, the native HER2/neu epitope peptide without Ii-Key and the immune system responded, demonstrating CD4+ and CD8+ T-Cells long-term memory*
Ii-Key-HA Avian Influenza Vaccine Phase I
H5N1 Avian Influenza
Ii-Key-HA* Peptide Vaccine Generates IgG Antibodies
The Ii-Key-HA vaccine has 100% homology between H5N1 Avian and H1N1 Swine Flu:
Opportunity to work with China CDC to develop Ii-Key HA peptide vaccine for emerging G4 EA H1 Swine Flu
Phase I Human Clinical Trial:
- 110 healthy subjects vaccinated
- Twelve (10) li-Key-HA hybrid peptides to H5N1 synthesized
- Ii-Key-HA peptides (500 μg) administered IM
- 21-day booster (500 μg)
- Safe & well tolerated
Checkpoint Inhibitors (CPIs) are Being Used as Front-line Therapy for Multiple Cancers
Immuno-Oncology Development Rationale:
- CPIs Need Immune Activators to Optimize Effectiveness
- Ii-Key Immunotherapeutic Peptide Vaccines Activate CD4 & CD8 T-Cell Responses
- Study Design: Usual Care with CPIs +/- Ii-Key Vaccines
- Front-line Opportunity
FOCUS ON COMBINATION THERAPY WITH CHECKPOINT INHIBITORS
Head & Neck
Brain – GB
Brain – AstroCyt
The foundational “Platform Patents” for Ii-Key technology focus on methods of increasing the antigen-specific activation of CD4+ T cells. This cell type is a critical component of the immune system, involved both in the recognition of new pathogenic agents as well as in autoimmune syndromes. The first technology platform (Ii-Key hybrid) relates to a means for increasing the vaccine potency of virtually any protein and while the second (Ii-suppression) relates to generation of an effective cell-based vaccine.
This group of patents relate more specifically to the use of the platform technologies for generating anti-cancer vaccines. We have generated Ii-Key hybrid compounds specifically for patients with breast, prostate, bladder, melanoma and HPV-related cancers.
These patents cover:
- Compositions and Methods Related to Ii Technology
- Ii hybrid peptides used for the enhancement of antigen presentation
- Constructs for the expression of Ii-Key/antigen epitope fusion peptides
- Hybrid Ii-Key/antigen epitope fusion peptides
- Methods for inhibiting Ii expression