Candidate: Ii-Key-CoV-2 peptide vaccine
Type: Vaccine based on Generex’s Ii-Key immune system modulation technology platform
2021 Status: Generex and its majority owned public entity NuGenerex Immuno-Oncology, Inc., said February 10 in a regulatory filing that Generex received a $2 million wire transfer two days earlier from investor partners in China toward its COVID-19 vaccine development initiatives. Those partners included Beijing Youfeng International Consulting, National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, and Beijing Guoxin Haixiang Equity Investment Partnership. To date, Generex said, it has received $3 million toward COVID-19 vaccine development initiatives from the Chinese investor partners.
2020 Status: Generex said December 31 that its majority owned public entity, NuGenerex Immuno-Oncology (NGIO) has filed for and expects to receive a trademark for The Complete Vaccine™. Generex defines a “complete vaccine” as one designed to regulate the immune system to provide a targeted, neutralizing antibody response without generating off-target, non-neutralizing antibodies that can lead to antibody dependent enhancement of disease. The company also defines a complete vaccine a one that activates “appropriate” T cell responses to yield long-term immune memory without activating detrimental Th2 responses that have been associated with immune-related complications of COVID-19.
NGIO has completed T cell assays and HLA typing of blood samples from 46 convalescent COVID-19 patients and 30 healthy pre-COVID donors (from 2017 and 2018), screening the immune regulatory activity of 33 Ii-Key epitopes. The T cell screen showed that numerous Ii-Key epitopes activate CD4+ Th1 and CD8+ responses. None of the Ii-Key epitopes tested activated any negative Th2 responses, Generex said.
Generex added that it has initiated GMP production of several Ii-Key-SARS-CoV-2 epitopes that will be formulated for Phase I and Phase II clinical trials, based on the results of the ex-vivo human studies. An IND is being prepared for FDA submission in early 2021.
Ii-Key epitopes have been used to bind and purify IgG antibodies from convalescent COVID-19 patient samples. The antibodies are being tested against live SARS-CoV-2 virus in a level 3 biocontainment laboratory to ensure that they neutralize the virus. Once confirmed as neutralizing, the Ii-Key epitope binding antibodies can be purified and genetically engineered to develop antibody therapeutics against COVID-19, according to Generex.
Investment holding company Bintai Kinden Corp. Berhad of Malaysia said September 18 it signed an amendment to a memorandum of understanding the companies inked in August for the development and commercialization of Generex’s Ii-Key-SARS-CoV-2 coronavirus vaccine. Bintai agreed to pay Generex an up-front $2.5 million licensing fee within two weeks, as well as 100% of the funding required for commercial development of the Ii-Key-CoV-2 vaccine—including laboratory work, manufacturing, regulatory filings, and the clinical development program for regulatory approval of the vaccine in Malaysia.
Upon approval of Ii-KeyCoV-2 in Malaysia, Bintai agreed to pay Generex a $17.5 million milestone payment, plus royalties on sales of the vaccine equal to $3 per dose on government sales and $4.50 per dose for private-sector sales. Generex said in August, it will earn royalties on sales of the vaccine—with potential revenues of up to $150 million. Bintai retained the right of first refusal for the Ii-Key-SARS-CoV-2 vaccine in Australia, New Zealand, and countries with Halal economies, particularly in Southeast Asia.
Generex and Bintai agreed to simultaneously implement different stages of development and production to speed up development; conduct clinical trials in and outside Malaysia; and build global manufacturing capacity.
In May, Generex announced what it called a key milestone in its COVID-19 vaccine program, the manufacturing of 33 Ii-Key-SARS-CoV-2 peptides using antigenic epitopes predicted by computational vaccinology algorithms. Provisional patent applications have been filed for the Ii-Key-SARS-2 peptides, which Generex’s NuGenerex Immuno-Oncology (NGIO) subsidiary plans to advance against SARS-CoV-2.
Upon passing quality assurance testing, the peptides will be shipped to the clinical laboratories conducting the “Ex-Vivo” Human Immune System Screening Program, using blood and plasma samples from patients who have recovered from COVID-19 that have already been collected and stored.
The top-performing Ii-Key-SARS-CoV-2 peptides will be selected, Generex said, for a “Complete Vaccine” designed to promote immune memory and potential long-term protection from coronavirus infection by stimulating B-Cell production of neutralizing antibodies and activate CD4+ T-Cell responses (TH1). The program will also address the safety of Ii-Key-SARS-CoV-2 peptides using a validated in-vitro assay that models the dangerous cytokine storm associated with COVID-19.
In March, Generex said it has been in talks with the Biomedical Advanced Research and Development Authority (BARDA) and the U.S. Departments of Veterans Affairs and Health and Human Services, as well as with authorities in Canada, Greece, Iceland, Indonesia, Italy, Philippines, Romania, Saudi Arabia, and the U.K. for licensing Ii-Key-SARS-2 peptide vaccines as well as new, patented immunotherapy technology allowing those countries co-ownership of the Intellectual Property in their territories.
A week earlier, Generex said it would spin out NGIO into a separate public company focused on advancing Ii-Key peptide vaccines into development to treat and prevent COVID-19 and other infectious diseases, as well as cancer, with partners in the U.S. and China. Generex filed a Form 10 Registration Statement for NGIO, to be effective in 60 days.
Earlier, Generex said it will use EpiVax’s computational tools to predict epitopes that can be used to generate peptide vaccines against SARS-CoV-2 using li-Key technology. The companies reached agreement after EpiVax identified a number of hotspots in the amino acid sequences of SARS-CoV-2 proteins.
Using epitopes predicted by EpiVax, Generex agreed to manufacture a series of synthetic amino acid peptides that mimic the epitopes of the virus and send them to Chinse researchers for testing in blood samples from patients who have recovered from COVID-19. The research team plans to select the best Ii-Key hybrid peptides to create a commercially viable vaccine that can proceed to human testing, Generex said.
According to the company, NGIO’s Ii-Key antigenic peptides have been shown to supercharge the immune system up to 100 times more than peptides alone.
Generex said in February it received a contract from the China Technology Exchange, Beijing Zhonghua Investment Fund Management Co. Ltd., Biology Institute of Shandong Academy of Sciences, and Sinotek-Advocates International Industry Development (Shenzhen) Co. Ltd. to develop a Ii-key vaccine. Generex said it would receive $1 million upfront to initiate project work in the U.S., a $5 million licensing fee for the Ii-Key technology, payment by the Chinese consortium for all costs and expenses related to the development of a COVID-19 vaccine, and a 20% royalty on each dose of vaccine produced.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: