GeoVax is conducting two Phase II COVID-19 vaccine clinical trials with its GEO-CMO4S1 vaccine. One of the trials is among immunocompromised patients.
Two major challenges in viral vector technologies are coding capacity – how much material can fit inside the vector – and manufacturing capabilities. GeoVax’s viral vector platform potentially overcomes both of those issues, enabling a broader immune system response and a manufacturing system able to quickly produce at scale and deliver vaccines successfully worldwide.
To illustrate the problem, “Think about the malaria vaccine, for example. It’s about 30% effective and requires four doses. As a vaccine, it’s inadequate, needing improved efficacy and simpler administration,” David Dodd, chairman and CEO of GeoVax, told BioSpace. “A better way to develop an acceptable malaria vaccine might be to encode elements from the genetic structure at different stages of malaria to induce a broader immune response, but limitations in coding capacity for most vaccine platforms don’t allow that.”
GeoVax’s platform directs the in vivo production of multiple viral proteins using a modified Vaccinia Ankara (MVA) delivery vector. “The MVA can encode multiple viral proteins resulting in the induction of strong and broadly specific immune responses with both antibody and T-cell effector function,” Dodd said. In contrast, other vaccine platforms, such as mRNA or adenovirus vectors can encode only a single viral protein.
“In the case of COVID-19 vaccines, the mRNA and adenovirus platform vaccines (Pfizer/BioNTech and Moderna for mRNA; J&J and AstraZeneca for adenovirus viruses) only incorporate the spike (S) protein, which induces neutralizing antibodies and limited cellular immunity. In contrast, the GeoVax MVA-based COVID-19 vaccine, GEO-CM04S1, encodes the S-protein and the nucleocapsid (N) protein, which induces both strong antibody and strong T-cell responses,” Dodd said, explaining that T-cell responses are critical to establishing functional responses with long-term durability and immunological memory.
The GeoVax MVA manufacturing process is also being developed to overcome manufacturing capacity issues by using continuous cell line manufacturing rather than the traditional chicken embryo fibroblasts that have been used historically for MVA vaccines. This enables significantly more vaccine to be produced in less time, which allows a faster response to high volume requirements associated with infectious disease outbreaks and epidemics.
The MVA-based vaccines also can be lyophilized – freeze-dried – to bypass the cold-chain or frozen-state requirements of many other vaccines. “As such, our focus is on developing vaccines that can be delivered and administered to those in need, regardless of where in the world they are located (e.g., tropical, rural or far-away areas),” Dodd said. With a BARDA-funded partner, GeoVax is working to transfer its vaccine into a microneedle format so it can be self-administered.
GeoVax is conducting two Phase II COVID-19 vaccine clinical trials with its GEO-CMO4S1 vaccine. One of the trials is among immunocompromised patients who have been treated with CAR T therapy or have undergone bone marrow transplants. As a result of such cancer therapy, those patients have had their immune systems severely abated.
Overall, immunocompromised patients constitute approximately 3% of the U.S. population – essentially, 10-12 million people. “Such patients are not being adequately served by the current authorized COVID-19 vaccines,” Dodd said. He said he believes this is the first trial of a COVID-19 vaccine in an immunocompromised population with a direct comparison of GEO-CM04S1 to the Pfizer/BioNTech vaccine. Application to immunocompromised populations “is our major point of differentiation. Phase I data of this multi-antigen vaccine showed strong neutralizing antibody and T cell responses,” he added.
This Phase II trial is being conducted at the City of Hope in Los Angeles, which developed the GEO-CM04S1vaccine that GeoVax licensed. This trial is currently in active recruitment and enrollment.
“The second Phase II trial evaluates GEO-CM04S1 as a booster in healthy people who have received a primary mRNA vaccine,” he said. With those vaccines, “there appears to be a rapid waning of immune response, resulting in the need for third and fourth shots. In general, a heterologous booster ought to provide a more robust and more durable immune response than simply adding another mRNA booster, especially if the booster results in both antibody and cellular immunity. This trial is currently recruiting and enrolling patients.” He said he expects to follow these trial participants for at least one year to gauge durability of response.
Additionally, Dodd said, “We have developed a single-dose pan-coronavirus vaccine candidate (GEO-CM02) that is progressing to an investigational new drug (IND) filing. It includes the spike protein (S) to induce the antibody immune response, and membrane (M) and envelope (E) proteins to induce T-cell immune responses.” Dodd explained that incorporating those three proteins – hopefully – will enable the vaccine to work effectively against future coronavirus variants without the need for reformulation. “We’re essentially targeting variants before they arise, rather than chasing after them.”
Data for that pan-coronavirus vaccine was presented at the World Vaccine & Immunotherapy Congress last December. As Dodd recounted, “We presented animal data that demonstrated 100% protection in a single dose in a lethal challenge model. Such results are unprecedented and are the basis of our current IND-enabling COVID-19 pan-coronavirus program.”
GeoVax also is developing therapeutic vaccines for oncology indications. “We believe therapeutic vaccines will provide the opportunity to enhance the utility of standard of care treatments and specifically, immune checkpoint inhibitors,” Dodd said. To that end, GeoVax is conducting IND-enabling work for a cancer vaccine using an MVA-VLP-MUC1 cancer immunotherapy to target solid tumors. This vaccine stimulates the immune system and heightens its response. Then, by combining it with an immune checkpoint inhibitor, it enables a significantly greater response.
In the future, Dodd said he envisions incorporating additional tumor-associated antigens beyond MUC1, such as cyclin B1, into the company’s immuno-oncology platform and development programs.
Additionally, GeoVax recently in-licensed Gedeptin, a Phase II stage cancer immunotherapy which is in an active, expanding multi-site trial addressing advanced head and neck cancers. This vaccine has also been granted orphan drug status and the clinical trial is partially funded by the FDA Orphan Drugs Clinical trial program. Since acquiring the worldwide rights to Gedeptin and the respective technology, GeoVax has expanded the trial sites and assigned CRO oversight to accelerate the completion of the patient enrollment and evaluation of this Phase II program.
Vaccines, whether therapeutic or for infectious diseases, are becoming more capable as the field advances beyond the current generation of products and treatment options. Longer durability and pan-coronavirus applications, therefore, will be expected. GeoVax plans to meet those expectations.
