San Diego—The vaccine developer Vaxart is aiming to get back on track after a turbulent year.
Over the past year and a half, the company has found itself entangled in the web of changing priorities at the US Department of Health and Human Services (HHS). In February 2025, HHS hit Vaxart with a stop-work order, forcing it to put a halt to a planned 10,000-person trial for its oral COVID-19 vaccine. The department lifted the order 3 months later only to hit Vaxart with another one in August. The two eventually came to a détente: Vaxart could complete the trial, a Phase 2b study, with the 5,000 people it had already enrolled, but it wouldn’t be allowed to hit the 10,000-person mark originally planned.
“Our vision, one day, is that this could be your vaccine pack.”
Soon, Vaxart’s 70-person team will learn whether those efforts have come to fruition. The company is weeks away from a top-line readout from the Phase 2b trial, which will reveal whether Vaxart’s oral COVID-19 vaccine was safe and effective, relative to a messenger RNA (mRNA) shot, in 400 participants.
As of Monday, speaking in an interview with C&EN at the BIO International Convention in San Diego, CEO Steven Lo and chief scientific officer Sean Tucker didn’t know what the result will be. They were waiting for the Biomedical Advanced Research and Development Authority (BARDA), which has funded the trial, to give them the go-ahead to unblind the data. Then, they’ll be able to see whether the oral COVID-19 vaccine has a future.
“Best case, you could be looking at end of 2028, sometime in 2029, where this technology will be out in the marketplace,” Lo says.
The pros of a vaccine pill
Vaxart’s vaccine pills are Tucker’s brainchild. His team takes weakened adenoviruses, inserts DNA that codes for a viral protein inside, and then dries them out and coats them so they’ll survive in the inhospitably acidic environment of the human stomach.
“So you swallow this, it gets intact through the stomach, and it gets into the intestine, where in that intestinal lining, the vaccine gets out, infects the epithelial cells. It then makes a COVID protein, along with a signal that tells it that it’s not food; it’s a pathogen. And then your immune system goes after that protein of interest, because you’ve activated in these wet surfaces,” Tucker says. Inducing an antibody and T-cell response throughout the body, including in the mucosa, would be an advantage over the blood-based immunity of existing COVID-19 vaccines.
Lo and Tucker believe—and hope—that in the face of increasing vaccine hesitancy, a pill vaccine is an easier sell than a shot. A pill could also be easier to distribute once approved. Unlike shots, which require healthcare providers to administer them, pills could be shipped directly to people’s homes.
The US Food and Drug Administration has not been particularly open to new COVID-19 vaccines during President Donald J. Trump’s second term. And turmoil at the agency, including the recent departures of top brass including Commissioner Marty Makary, has created unwelcome uncertainty for drug developers beyond just vaccine makers. But Vaxart has worked consistently with the same set of reviewers at the agency, Lo says.
In fact, one of the changes Makary began implementing before his departure could be helpful to Vaxart. Makary had called for all new and updated vaccines to be compared with placebos rather than standard of care. Vaxart’s Phase 2b study—greenlit and launched before Makary’s arrival—requires that the COVID-19 vaccine pill be compared against an mRNA vaccine, which means that every participant must receive both a pill and a shot in order to keep the study blinded. Participants receiving an active COVID-19 vaccine pill receive a saline shot alongside it; those getting an mRNA vaccine shot also get a sugar pill. If future studies need only involve pills, Vaxart won’t have to spend time or money on saline or mRNA shots.
“We’re prepared for whatever the FDA wants,” Lo says.
Finding more finance at BIO
Vaxart is also advancing vaccine pills for norovirus, influenza, and human papillomavirus (HPV). At BIO, Lo and Tucker are looking for partners to help finance those trials.
In November last year, the company Dynavax Technologies paid Vaxart $30 million up front—$25 million cash, $5 million equity—to license the COVID-19 vaccine pill and for the option to keep developing it. Sanofi agreed to acquire Dynavax the very next month. Now Sanofi is effectively Vaxart’s partner, which will be good news if the readout is strong and Sanofi elects to proceed. “They are in the vaccine business, they are well kept and certainly have global reach, and so we’re delighted that we’re able to now work with them during this partnership,” Lo says.
The BARDA and Dynavax funds are sufficient to fund the COVID-19 vaccine-pill study, but otherwise, Vaxart is looking at a cash runway that will run out next year.
“Our vision, one day, is that this could be your vaccine pack,” Lo says, picking up a blister pack of four small, round, white pills. (These are placebos, not the adenovirus pills, he says.) “You’ve got COVID, flu, norovirus, add the fourth one in terms of what could be important to you. I think that’s where there’s opportunity.”
