Novavax Inc., one of the first biopharma companies to reveal its efforts to develop a SARS-CoV-2 vaccine in January, has identified a prefusion protein for testing in an Australian phase I trial, slated to start in mid-May.
The company has yet to file an IND, but Gregory Glenn, its president of R&D, told BioWorld his team expects to have an initial readout in July and could potentially be encouraged to move to an efficacy-focused phase IIb study in the U.S. and other countries soon after.
The result of that phase IIb study could potentially form the basis for provisional approvals in the U.S. and Europe, he said. "I don't think that would negate the need to do the next stage of a trial, but you can also imagine they would be using it," he said. "It's not normal times."
The candidate, NVX-CoV2373, is going to have "a very similar safety profile" to Novavax's phase III Nanoflu nanoparticle vaccine and, given preclinical findings, appears to be stable and productive, Glenn said. "The conformation is exactly what you need. And now we're seeing that manifest after immunizing animals [in which we're seeing] very, very high neutralizing antibody, which I think everyone would agree is highly likely to be protective," he added.
In the phase I trial, investigators will be looking for receptor binding/blocking antibodies and neutralizing antibodies. “If we had those, we would move into a phase IIb with a lot of confidence," Glenn said.
The Gaithersburg, Md.-based company is developing the vaccine through two different work streams, one directed toward to transferring its production technology for the vaccine to its partner, Emergent Biosciences Inc., and the other toward getting the phase I up and running. The efforts have been supported with preliminary funding from the Coalition for Epidemic Preparedness Innovations, which in March awarded Novavax $4 million. Additional funding discussions are ongoing.
Novavax (NASDAQ:NVAX) shares climbed 15.3% on April 8 to close at $17.18.
Therapeutic efforts advancing, too
Wednesday also welcomed a string of updates on the therapeutic front, with updates from Bellerophon Therapeutics Inc., Oncoimmune Inc. and Moleculin Biotech Inc., each of which is advancing entrants in the global race to aid patients facing challenges from COVID-19.
Bellerophon, which is already running preliminary tests of its iNOpulse system for pulmonary delivery of nitric oxide (NO) under an emergency expanded access program, said it has submitted an IND seeking the FDA's blessing to formally test the system in a much larger study. It is also seeking funds to support its work from BARDA and the NIH.
To date, three COVID-19 patients have completed treatment with iNOpulse, with several additional patients currently on the therapy. Those three have already demonstrated improved oxygenation that allowed them to avoid the need for mechanical ventilation and two have already been discharged, Bellerophon CEO Fabian Tenenbaum, told BioWorld.
With iNOpulse, Bellerophon is trying to help patients to improve oxygen saturation in their blood and avoid progression to the hyperinflammatory stage of the illness in which many develop acute respiratory distress syndrome (ARDS), at which point mortality rises substantially, he said.
The open-label trial, which if approved as proposed would enroll up to 500 patients with COVID-19, will randomize patients to treatment with either standard of care (SOC) or iNOpulse plus SOC. Called PULSE-CVD19-001, it will focus on enrolling and treating those patients who require SOC oxygen supplementation.
Investigators will use an adaptive statistical approach to analyze the data on a rolling basis, as they come in, looking at a primary endpoint of disease progression. "If the trial demonstrates sooner than 500 – let's say its 200 patients – that there is now a clear benefit between active and standard of care, we can stop the trial early and move to an accelerated approval," he said.
Bellerophon shares (NASDAQ:BLPH) shares fell 8.8% to close at $11.20.
Two other companies announcing progress on their COVID-19 programs on Wednesday included Rockville, Md.-based Oncoimmune and Houston-based Moleculin.
Privately held Oncoimmune reported receiving FDA approval to proceed with a phase III trial testing the safety and efficacy of its lead clinical candidate, CD24Fc, a fusion protein it has been testing for the prophylactic treatment of acute graft-vs.-host disease. The potentially first-in-class biologic "fortifies an innate immune checkpoint against excessive inflammation caused by tissue injuries," said Yang Liu, Oncoimmune's CEO and co-founder. Whether that holds true in COVID-19 patients will be shown by the company's upcoming study.
In a trial slated to enroll up to 230 patients with severe clinical symptoms of COVID-19, patients will be randomized to either a single dose of CD24Fc or placebo, following up with a 14-day period to assess safety and efficacy in clinical improvement. The double-blind study, called SAC-COVID, consists of two interim analyses, first for safety and therapeutic activity and then for therapeutic efficacy.
Moleculin is also moving toward the clinic, with plans to submit an IND of its own for testing the 2-deoxy-D-glucose ester-type prodrug WP-1122 against the virus following its receipt of encouraging preclinical data.
In a pre-print article submitted by researchers at the University of Frankfurt to Nature Research on March 11, Moleculin said, scientists reported that "blocking glycolysis with non-toxic concentrations of 2-DG prevented SARS-CoV-2 replication in Caco-2 cells." Moleculin CEO Walter Klemp said the report was "the breakthrough we were looking for," though it came "from an unexpected source."
With the safety of WP-1122 already established in mice, the company is now working to demonstrate safety in other animal models before submitting an IND, Moleculin said. Shares of Moleculin (NASDAQ:MBRX) climbed 125.7% to $1.27 on Wednesday.