Can GeoVax Labs’ dual-antigen COVID-19 vaccine succeed where leading messenger RNA (mRNA)-based jabs developed during the pandemic have faded, clinically and commercially?
The company will begin to find out as it launches a 10,000-participant Phase IIb trial comparing the efficacy, safety, and immunogenicity of its next-generation, dual-antigen COVID-19 vaccine GEO-CM04S1 to one of the current FDA-approved COVID vaccines—a study being funded by the Biomedical Advanced Research and Development Authority (BARDA).
BARDA has awarded GeoVax approximately $24.3 million through its Rapid Response Partnership Vehicle (RRPV) to fund the manufacturing of clinical materials for the randomized, double-blinded Phase IIb trial, as well as regulatory and other support activities for the study. GeoVax could receive up to $45 million through RRPV based on meeting technical and scientific milestones.
Through its Clinical Studies Network, BARDA will also award approximately $343 million from its Project NextGen program to fully fund an as-yet-undisclosed contract research organization (CRO) that will carry out the Phase IIb trial. The Network offers services for Phase I through IV clinical trials of medical countermeasure candidates such as vaccines and treatments.
Investors responded to the BARDA award announcement June 18 by sending GeoVax shares rocketing 71% from $1.11 to $1.90. Those shares have fluctuated early this week, surging another 30% to $3.03 on Monday before dipping 27% to $2.20 on Tuesday.
GeoVax Chairman, President, and CEO David A. Dodd told GEN his company and the CRO have worked for over a year in preparation for the start of the Phase IIb trial.
GEO-CM04S1 is based on GeoVax’s MVA viral vector platform, which supports the presentation of multiple vaccine antigens to the immune system in a single dose.
Two-prong attack
While current COVID-19 vaccines such as Pfizer/BioNTech’s Comirnaty and Moderna’s Spikevax are mRNA vaccines targeting the Spike protein, GeoVax’s GEO-CM04S1 mounts a two-prong attack on SARS-CoV-2 by encoding for both the spike (S) and nucleocapsid (N) antigens of the virus. The vaccine is designed to induce both durable neutralizing antibody and T-cell-based immunity against current and future variants of SARS-CoV-2 by attacking parts of the virus that are less likely to mutate over time.
By pursuing a more broadly functional engagement of the immune system, GEO-CM04S1 is designed to protect against severe disease caused by continually emerging variants of COVID-19—and thus should not require frequent and repeated modification or updating, according to GeoVax.
GEO-CM04S1 is already under study in three Phase II trials. One trial is assessing GEO-CM04S1 as a primary vaccine in immunocompromised blood cancer patients who have received cell transplants or CAR-T therapy (NCT04977024). The study’s open-label portion has generated data showing GEO-CM04S1 to be highly immunogenic in these patients, inducing both antibody responses, including neutralizing antibodies, and T-cell responses.
“We expect that this year there will be another update. We also expect that as we go into early 2025, we anticipate expanding that trial to additional sites in North America as well as in the U.K.,” Dodd said.
The other two trials are evaluating GEO-CM04S1 as a:
- Booster vaccine for healthy adults who have previously received the Pfizer or Moderna mRNA vaccines (NCT04639466). The trial was fully enrolled in September 2023 and final results are expected in the fourth quarter, reflecting a 12-month tracking of study patients.
- Booster vaccine in immunocompromised patients with chronic lymphocytic leukemia (CLL), a high-risk population for which current mRNA vaccines and monoclonal antibody (MAb) therapies have been shown to offer inadequate protective immunity (NCT05672355). GeoVax expects to read out data in the fourth quarter.
‘The reason why that becomes important to us is, if the data looks good, we may very well initiate our own company sponsored CLL trial,” Dodd said. “The various discussions we’ve been having with regulatory authorities indicate that there may be an expedited pathway for registration by focusing on such a high-risk group that is recognized as not being satisfied or addressed adequately by what is out there right now.”
GeoVax says its COVID-19 vaccine is potentially more durable than current FDA-approved COVID-19 jabs, which have been shown to lose effectiveness within two to six months.
“We’re showing protective immunity from the original Wuhan through the Omicron XBB1.5 variant, so it offers breadth of protection across the variants as well as durability,” Dodd said.
Longer durability
GeoVax says its studies to date have shown the effectiveness of GEO-CM04S1 to last twice as long as the two to six month range of current COVID-19 vaccines: “Our durability currently is coming in from our clinical trials at 8 to 12 months,” Dodd added.
And where Pfizer/BioNTech and Moderna developed COVID-19 vaccines aimed at protecting the general population from the virus, GeoVax says its COVID-19 jab is intended for immunocompromised adults who are more likely to potentially experience severe COVID-19 symptoms, hospitalization, and increased risk of death, yet are less likely to respond adequately to current COVID-19 vaccines.
The number of immunocompromised adults is estimated at between 50 million and 70 million people in the U.S. and up to 300 million worldwide.
“We’re not planning on going toe to toe with the current vaccines,” Dodd said. “From day one of moving forward with our vaccine, we have focused on going after the populations for whom the pandemic has never ended, the immunocompromised populations who have medical conditions that have depleted their body’s ability to respond to COVID or SARS-CoV-2.”
“These patients remain at risk of severe disease, hospitalization, and risk of death. They’re under active medical care they’re being managed by hematological oncologists, or they might be managed by the nephrologist, or by the endocrinologist if they have diabetes. They have medical conditions in which they are under active medical care. That’s different than the general population,” Dodd explained.
By focusing on immunocompromised patients, GeoVax reasons it can maximize potential revenue for its vaccine as revenues for the approved COVID-19 jabs has plunged with the pandemic evolving into an endemic.
$7.4B U.S. revenue potential
In its corporate overview presentation to investors this past spring, GeoVax estimated the market revenue potential for GEO-CM04S1 in the U.S. alone at $7.4 billion—just below the combined $8 billion in combined 2024 global sales that Pfizer has projected for both its COVID-19 vaccine Comirnaty® (co-marketed with BioNTech) and its COVID-19 drug Paxlovid®.
Dodd says GeoVax is updating its revenue projection because the spring forecast was based on an older estimate of just 20 to 25 million immunocompromised Americans—while the National Health Interview Survey of the U.S. Centers for Disease Control and Prevention cites between 50 million to 70 million Americans with compromised immune systems.
“From a business standpoint, we believe that we have the opportunity with our vaccine to be the lead vaccine to be used among people with compromised immune systems, because they’re not benefiting from what is currently out there,” Dodd said.
GeoVax has not furnished a peak annual sales estimate for GEO-CM04S1
Last year, Comirnaty generated $11.220 billion in direct sales and alliance revenues, down 70% from $37.806 billion in 2022, while Paxlovid generated only $1.279 billion in 2023, down 93% from $18.933 billion a year earlier.
Moderna’s COVID-19 vaccine Spikevax racked up $6.7 billion in 2023 sales, a 64% plunge from $18.4 billion in 2022. For this year, Moderna has only disclosed a $4 billion combined sales projection for its respiratory vaccine franchise, which includes Spikevax as well as its respiratory syncytial virus (RSV) vaccine mRESVIA (mRNA-1345), approved by the FDA on May 31.
The BARDA award marks a milestone for GeoVax. Based in the Atlanta suburb of Smyrna, GA, GeoVax was founded in 2001 with the initial focus of developing an HIV vaccine, based on research by Harriet Latham Robinson, the company’s founder and chief scientific officer emeritus.
Pivot from HIV
Dodd joined GeoVax’s board in 2010, and the following year was first elected chairman. As chairman, Dodd oversaw the company’s pivot away from HIV in 2014 after it failed to attract funding from investors or the NIH to advance its vaccine past Phase IIa.
The company began pursuing vaccine development based on its MVA platform, with early signs of success. GeoVax’s Ebola Zaire vaccine, for example, showed 100% protection in non-human primates given a single dose without any adjuvants, while the company also developed vaccines for Ebola Sudan and Marburg virus.
“We’re not planning on carrying those forward on our own funding, but we’re in discussions right now” with potential partners to move toward Phase I studies, Dodd said. Should those talks yield one or more agreements, he said, the resulting studies “will be done through funding by non-dilutive means.”
Dodd took on the additional roles of president and CEO in 2018, intent on enabling GeoVax to develop its pipeline by growing and broadening the company’s financing.
As COVID-19 began to wreak havoc on the world, GeoVax began a program to develop a vaccine for the virus. That sent the company’s stock, then trading Over the Counter, zooming from 13 to 50 cents a share. But by June 2020, with the world upended by the pandemic, GeoVax was down to five employees and $100,000 in available cash.
Three months later, GeoVax closed on a $12.8 million public offering and up-listed its publicly traded shares and warrants from the Over the Counter market to Nasdaq.
In 2021, GeoVax acquired its two main pipeline programs, shelling out undisclosed sums for an exclusive license from City of Hope to develop GEO-CM04S1 two months after the company bought exclusive rights to the cancer drug Gedeptin® from PNP Therapeutics.
Gedeptin is now in a Phase I/II trial (NCT03754933) in patients with advanced head and neck cancer. Initial study results from the first trial of the Phase II portion are expected to be announced within the next two to three weeks, Dodd said, to be followed by plans for an expanded Phase II study of Gedeptin, then a combination study evaluating Gedeptin with an immune checkpoint inhibitor.
The FDA has granted Gedeptin orphan drug status for the intra-tumoral treatment of anatomically accessible oral and pharyngeal cancers, including cancers of the lip, tongue, gum, floor of mouth, salivary gland and other oral cavities.
Also in GeoVax’s pipeline is GEO-MVA, a vaccine for smallpox and Mpox being developed for adult men at high risk of Mpox. GeoVax aims to become the first U.S. based supplier of a vaccine for Mpox and smallpox (Copenhagen-based Bavarian Nordic began commercial launch of the currently sole FDA-approved Mpox vaccine, Jynneos® [MVA-BN] in April), plus satisfy interest from the federal government in replenishing and re-stocking the Strategic National Stockpile with a domestic-sourced smallpox vaccine.
Progress report
GeoVax plans later this year to disclose its progress toward an expedited regulatory registration pathway. “Frankly, we believe that our first product to be registered and commercialized could very easily be GEO-MVA as a standalone vaccine,” Dodd said. “I’m not saying it will be commercialized. But we’ll have updates on that, because development is being driven by a heavy regulatory strategy, as you might imagine.”
GeoVax’s pipeline also includes a half dozen preclinical programs—including a treatment for solid tumor cancers, and vaccines for pan-coronavirus, Ebola Zaire, Ebola Sudan, Marburg virus, and Zika.
“Those products will advance to the degree that there is non-dilutive, let’s say external collaboration, business development, or co-development funding. We’re not allocating a lot of time to those if any,” Dodd said.
Despite data showing 100% protection in a single dose for its Zika virus candidate, Dodd said, “it has not been a priority, because there are others out there that are going after it.”
“That’s one program that is held in discussions if there are potential partners, and whatever form of a transaction they may end up thinking about,” Dodd added. “Our focus is, number one, the [BARDA-funded] Project NextGen program for GEO-CM04S1, then number two, both the GEO-CM04S1 Phase II programs and the Gedeptin program.”
Project NextGen is a $5 billion program designed to speed up development of next-generation COVID-19 vaccines, drugs, and enabling technologies that lower costs, speed production, increase efficacy, and improve access to those vaccines and drugs. Project NextGen is led by BARDA and the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
To date, BARDA says, it has spent more than $2 billion in Project NextGen funding to support development of next generation vaccines, treatments, and enabling technologies. BARDA is part of the U.S. Department of Health and Human Services (HHS)’s Administration for Strategic Preparedness and Response (ASPR).
GeoVax finished the first quarter with a $5.58 million net loss, up from a $4.038 million net loss in Q1 2023, and no grant revenue either quarter. The company reported a $26 million net loss in 2023, nearly double its $14 million net loss the previous year.
GeoVax has grown its workforce to about 25 people, Dodd said, up from the 17 the company reported in its Form 10-K annual report for 2023. That workforce is expected to grow over time through a combination of full-time and contracted employees: “We’re actually going through all that planning right now of what our timing will be and our options for staffing up.”
