COVID-2019 infections vaccine is being developed by Generex Biotechnology for the prevention of coronavirus infection (COVID-19 strain). The company will utilise li-Key peptide vaccine platform of NuGenerex Immune-Oncology (subsidiary of Generex Biotechnology), develop the product under Ii-Key COVID Complete Vaccine™ development programme. Major histocompatibility complex (MHC) class II associated invariant chain (Ii) derived Ii-Key peptide is involved in the regulation of the formation, trafficking, and antigen-presenting functions of MHC class II complexes, essential for the activation of T cells in the immune response. When the peptide is linked to an antigenic epitope, it displaces the resident antigens from the antigen binding grove on MHC Class II molecules. This renders the MHC molecules to present the Ii-Key epitope to selectively activate T-helper type 1 cells responses. These events increase the duration and intensity of the immune responses. The interaction reduces the binding affinity of the antigenic binding groove on the MHC class II molecule and any previously resident epitope is discharged. Preclinical development is underway in the US. Early research is ongoing in China.

Generex Biotechnology is seeking partnership opportunities to expand development of its COVID-2019 infections vaccine ^[1] .

As at April 2024, no recent reports of development had been identified for research development in COVID-2019-infections (Prevention) in China (Parenteral).

As at January 2025, no recent reports of development had been identified for preclinical development in COVID-2019-infections (Prevention) in USA (Parenteral).

In May 2021, Generex Biotechnology Corporation provided guidance on the terms of its agreement with Beijing Youfeng Biological Technology (Youfeng-BI) in connection with the $US2,000,000 payment made by Youfeng-BI to GNBT and its subsidiary NuGenerex Immuno-Oncology (NGIO) on or about April 27, 2021. Under the terms of this agreement, if YouFeng-BI conducts phase I, phase II, phase III clinical trials in accordance with ICH guidelines to support commercial approval of the Ii-Key SARS-Cov-2 vaccine by the NMPA (the Chinese FDA), then: (1) YouFeng will provide the clinical data to Generex for its US FDA and the international approvals in its current contracts as available; and (2) YouFeng shall have the exclusive sales rights in any country other than US, Canada and the countries, territories under GNBT’s current licensed out contracts, and Mexico, Ecuador, Peru and Colombia with respects to li-key SARS-Cov-2 vaccine (provided that YouFeng complies with clauses (1) and makes a commitment to execute clause (3) of this paragraph); and (3) Upon the technology is recognized by NMPA through this li-key SARS-Cov-2 vaccine, YouFeng will execute the payment terms of license fee for the entire Ii-key platform referred to in a contract previously executed by GNBT. Although YouFeng will obtain the exclusive sales rights mentioned above upon the satisfaction of the conditions mentioned above, Generex and NGIO will maintain worldwide patent rights to the Ii-Key SARS-Cov-2 vaccine, except for China. Additionally, Youfeng has agreed to provide GNBT with a complete development plan outlining the regulatory path, data requirements, pre-clinical and clinical studies planned, and regulatory filing timeline and copies of all NMPA filings to date and in the future. In November 2020, Generex Biotechnology Corporation closes its a licensing agreement with consortium of partners in China including Beijing Guoxin Haixiang Equity Investment, and Beijing Youfeng International Consulting for the development and commercialisation of the (Ii-Key-SARS-CoV-2) coronavirus vaccine in China. Under the terms of the deal, Generex will receive a licensing fee of up to $US50 million for the exclusive use of the Ii-Key vaccine platform for infectious disease and cancer in China and its territories. For each product developed using the Ii-Key technology under the platform license, Generex will receive an upfront payment, full funding for product development, regulatory approval, and commercialisation in China, a success fee upon product approval, and a royalty to be determined on a case-by-case basis ^{[2] [3] [4]}

In November 2020, Generex Biotechnology announced that their Ii-Key COVID-19 vaccine development partner Bintai Kinden Corporation have executed their exclusive option to license and distribute the Ii-Key-SARS-CoV-2 vaccine in Australia and New Zealand once the vaccine is developed and approved by the FDA and relevant Malaysian authorities. NuGenerex Immuno-Oncology, in October 2020, closed its licensing & distribution agreement with Bintai Kinden Corporation of Malaysia for the development and commercialisation of the Ii-Key-SARS-CoV-2 coronavirus vaccine. Under the terms of the agreement, Bintai will have an exclusive license to distribute the Ii-Key-SARS-CoV-2 vaccine in Southeast Asia, including Malaysia, Vietnam, Indonesia, and the Philippines. Additionally, Bintai has been given an option, with right of first refusal for distribution in Australia and New Zealand using its extensive connections to secure contracts in the region.In exchange for the license and distribution exclusivity, Bintai has paid an up-front licensing fee of $US2.625 million and has committed to funding 100% of the commercial development costs for the Ii-Key-CoV-2 vaccine including laboratory and pre-clinical work, GMP manufacturing in the US, and global phase I, phase II, and phase III clinical trials, and all clinical and regulatory work required for approval in each of the licensed Australasian countries. Earlier, in August 2020, Generex Biotechnology signed a memorandum of understanding (MOU) with Bintai Kinden Corporation of Malaysia for the development and commercialisation of the Ii-Key SARS-CoV-2 coronavirus vaccine of Generex. Bintai agreed to pay Generex upfront development fees and back-end licensing payments, and will pay 100% of the funding required for the commercial development of the vaccine. The development activities will include laboratory work, manufacturing, regulatory filings and the clinical development program for regulatory approval of the vaccine in Malaysia. In addition, upon approval of the vaccine in Malaysia, Generex will receive royalties on sales of the vaccine with potential revenues of up to $US150 million. Under terms of the MOU, Generex and Bintai agreed to collaborate and develop strategy with primary goals including streamlining of vaccine development process, conducting clinical trials globally and building global manufacturing capacity. Later, in September 2020, Generex Biotechnology and Bintai Kinden Corporation of Malaysia signed an addendum binding the terms of the previously signed MOU for the development and commercialisation of the Ii-Key SARS-CoV-2 coronavirus vaccine. Under the terms of the Addendum, Bintai and Generex will finalise the legal and contractual documentation for the contract, partnership, and licensing & research agreement, and Bintai will pay Generex an up-front licensing fee of $US2.5 million within two weeks. Additionally, Bintai will pay 100% of the funding required for the commercial development of the vaccine in Malaysia. Also, upon approval of the vaccine in Malaysia, Bintai will pay Generex a $US17.5 million milestone payment and Generex will earn royalties on sales of the vaccine equal to $US3 per dose on government sales and $US4.50 per dose in the private sector. Further, under this new Addendum, Bintai will have the right of first refusal for the vaccine in Australia, New Zealand, and the global HALAL markets, particularly in Southeast Asia. ^{[5] [6] [7] [8]}

In March 2020, Generex Biotechnology entered into a licensing agreement with Beijing Zhonghua Investment Fund Management and Sinotek-Advocates International Industry Development for the development of coronavirus vaccine (COVID-19 strain), using the Ii-Key peptide vaccine platform of NuGenerex immune-Oncology (NGIO), a Generex’s majority owned subsidiary. According to the terms of the agreement Ii-Key peptides linked with nCOV-2019 coronavirus epitopes will be generated by Generex Biotechnology through NGIO and will be tested against the blood samples of the patients in China recovered from coronavirus infection by the Chinese partners. The data obtained will indicate the Ii-Key-nCOV epitopes recognised by the human immune system, that will eventually be developed as the potential coronavirus vaccine by Generex Biotechnology. The human clinical trials will be conducted in China and the USA. The Chinese partners will have exclusive rights to use and commercialise the products in China and will make payments to Generex Biotechnology that include upfront payment of USD$ 1 million, development expenses, royalty on each dose of vaccine produced and $USD 5 million as a licensing fee for the Ii-Key technology upon completion of development and testing. Generex Biotechnology will may payments to NuGenerex Immuno-Oncology after the receipt of the licensing payments, since the intellectual property resides with the later. ^[9]

In August 2019, Generex Biotechnology announced for a planned spin-out of its subsidiary NuGenerex Immuno-Oncology (formerly Antigen Express), which will include the Ii-Key technology and AE37 immunotherapeutic vaccine program. Based on this spin-out, NuGenerex Immuno-Oncology will separate and work as a public company. ^[10]

In February 2021, Generex Biotechnology announced that it completed and released data from mouse immunogenicity study of COVID-2019 infections vaccine (Ii-Key-SARS-CoV-2 vaccine) with transgenic mice that was genetically engineered with a gene expressing the DR4 human leukocyte antigen (HLA) allele, for which the vaccine is specific ^[11] .

In December 2020, NuGenerex Immuno-Oncology filed trademark application for COVID-2019 infections vaccine (The Complete Vaccine™) and company also released pharmacodynamics data from a preclinical trial in COVID-2019 infections ^[12] .

In August 2020, Generex Biotechnology reported that it intends to conduct a meeting with the Canadian National Research Council to discuss the Ii-Key-SARS-CoV-2 vaccine technology forward ^[13] .

In April 2021, Generex Biotechnology announced that the company submitted a response package to the US FDA’s comments in their pre-IND written response. The package provides the data and information requested by FDA, including the Ii-Key epitope sequences selected based on results of the ex vivo blood screening programme, results of the transgenic (humanized) mouse immunogenicity study demonstrating vaccine-specific antibody production, GMP manufacturing information for the five Ii-Key-SARS-CoV-2 epitopes in the vaccine, and a revised protocol that incorporates FDA’s comments and requests ^[14] . Generex Biotechnology in February 2021, reported that it intends to submit IND application with the US FDA to proceed with phase I and phase II trials to evaluate safety and immunogenicity of the COVID-2019 infections vaccine. The company also plans to conduct trial in previously infected participants to determine if vaccination can activate the T cell immune response to generate long-term immune memory. In August 2020, the FDA delivered a written response to pre-IND briefing package for the clinical development program of COVID-19 vaccine in which they have agreed to the overall clinical plan and provided straight-forward guidance on protocol specifics and vaccine product data requests that will be addressed in the IND submission ^{[11] [15]} . In July 2020, Generex Biotechnology announced that US FDA has accepted the pre-IND briefing package for the clinical development program of COVID-19 vaccine against the SARS-CoV-2 coronavirus infections ^[16] . Earlier in the same month Generex Biotechnology submitted a pre-IND briefing package ^[17] .

In May 2020, Generex Biotechnology submitted a contract proposal to Biomedical Advanced Research and Development Authority (BARDA) to fund and support the development of a COVID-2019 vaccine against the SARS-CoV-2 coronavirus using the Ii-Key vaccine technology ^[18] .

In May 2020, Generex Biotechnology completed identification and selection of SARS-CoV-2 epitopes for development of vaccines. The company also commenced GLP manufacturing of synthetic Ii-Key-SARS-CoV-2 peptides for screening in ex vivo assays like cellular assays, antibody and virus neutralisation tests, and a in vitro cytokine storm cellular assay, using blood samples from COVID-2019 convalescent patients, in order to assess and select Ii-Key peptides that activate the immune system ^[18] .

Generex Biotechnology has initiated early research in coronavirus infections in China and the US ^[9] .

Financing information

In April 2021, Generex Biotechnology secured US$2 million from Chinese partners to provide research results, data, and necessary documents to support an IND submission to the Chinese National Medical Products Administration (NMPA) ^[19] .

In August 2020, Generex Biotechnology signed a letter of intent (LOI) with potential partners in China to develop the Ii-Key-SARS-CoV-2 vaccine for China with a proposed $US5 million upfront payment upon contract signing and minimum of $US400 million if the vaccine is proven successful in clinical trials ^[13] .

In December 2020, Generex filed an extensive patent application that covers our Ii-Key-SARS-CoV-2 vaccine and provides the foundation for a new patent estate for the Ii-Key platform ^[12] .