Investors who tuned in to Inovio Pharmaceuticals’ quarterly earnings call for signals on the fate of the company’s Phase I COVID-19 vaccine trial were largely disappointed- and the smattering of updates to the INO-4800 clinical programme that were disclosed weren’t necessarily going in the right direction.
With Moderna Therapeutics and Novavax each receiving stockholder payouts for promising early clinical data for COVID-19 vaccine candidates, Inovio wasn’t going to be left behind in the development space. However, its first disclosures haven’t gone as smoothly; the company released a very limited data set in June, where it said that 34 of 36 patients “demonstrated overall immune responses.”
The lack of any specific disclosures around the data drove investors to carve off nearly 20% off the company’s share price following the announcement. That uncertainty has been maintained in the interim, as a month later there was still no clarity on how the company’s DNA vaccine platform might compare to the competitors. (See ViewPoints: Dubious disclosures for Inovio's COVID-19 vaccine)
In the absence of a better look at its Phase I data, Inovio did offer up results from a non-human primate study of INO-4800, which it said was evidence of longer durability- nearly four months- than has been demonstrated by any of the competing vaccine platforms.
Inovio’s quarterly earnings call disclosed some new tidbits on its progress in the Phase I trial of INO-4800, now offering updated metrics for its observed immune responses. Now instead of 34 of 36 patients showing a response, 38 of 38 healthy volunteers “demonstrated overall immunological responses based on binding and neutralising antibody responses and T-cell immune responses,” with 95% experiencing seroconversion.
CEO Joseph Kim clarified that three patients had been excluded from the prior analysis in June on account of suspected COVID-19 exposure, but two of the infections were not confirmed. After accounting for one patient that dropped out of the study- plus what Kim described as “the luxury of having additional time to re-run those samples”- the reported response rate therefore managed to increase without any additional patients being enrolled.
The bigger picture
Inovio is hoping that a few defining features of the INO-4800 programme will allow it to rise to the top of the vaccine development pile; CEO Kim emphasised the value of its demonstration in non-human primates that its candidate can solicit both CD4 and CD8 T-cell responses- a feat that has not yet been accomplished by mRNA vaccines from Moderna or BioNTech. The company also emphasises the value of the stability of its DNA platform, which is stable at refrigeration for up to five years, and room temperature for one year- unlike the cold chain transport required by competitors. Further, its DNA delivery means that it won’t run into anti-vector responses that could limit re-dosing, should the product end up administered as a seasonal vaccine.
The company hasn’t shared much data on the safety profile of INO-4800, but noted that all six adverse events in the Phase I trial were mild. Kim hinted that this may support a differentiated safety profile for the product that could make it particularly amenable to high-risk groups like the elderly.
Further clarity on the murky immunogenicity data for INO-4800- with details like neutralising antibody titres- likely won’t come until publication of the Phase I dataset, which Kim said would happen in an undetermined time frame following peer review in “a top medical journal.” Importantly, he also noted that the company is aiming to start its Phase II/III trial of INO-4800 in September- likely before publication of the Phase I data.
In the meantime, Inovio has expanded the Phase I trial by 80 patients, and removed the upper age limit from the study. The trial was also expanded to include a new, lower dosing arm- though Kim was quick to note that the decision didn’t mean the company didn’t have confidence in the two doses it had initially selected, saying that “we wanted to see the overall spectrum of doses.”
However, the additional data collection will likely have an impact on Inovio’s regulatory plans; while it had originally a forecast seeking an emergency use authorisation (EUA) from the FDA for INO-4800 by year-end, that guidance has now been shifted to “sometime in 2021.”
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