Phase I data on immune responses induced by Inovio Inc.'s COVID-19 DNA vaccine candidate, INO-4800, showed it induced neutralizing antibodies and T-cell responses against all spike protein variants tested in a phase I study, including those first detected in the U.K., South Africa and Brazil. A preliminary report on the analysis, published on bioRxiv, preceded the reporting of phase II data on the candidate expected later this quarter as well as a potential move to phase III testing, pending resolution of a partial clinical hold on the study first announced in September 2020. Company shares (NASDAQ:INO) rose 2% to $9.01 on April 15.
The new findings show that neutralization levels of INO-4800 against the South Africa and U.K. variants – now dominant in the U.S. – were reduced to the levels similar to the previous reports of mRNA or viral vector vaccines. Surprisingly, though, clinical samples collected from strong responders in the phase I study also showed "full maintenance" of antibody titers again the P.1 variant, commonly known as the Brazilian variant, and “pretty good titers” against the South African variant, Inovio President and CEO J. Joseph Kim told BioWorld.
"The even better news is that Inovio's INO-4800 can generate both antibody responses and T-cell responses," he said, noting that the latter effect is important in maintaining long-term protective efficacy against SARS-CoV-2.
Findings documented in the paper were based on an analysis of clinical samples collected at varying timepoints post-immunization from a subset of high-responders among the 120 total participants in Inovio's phase I study (NCT04336410).
Antibodies capable of neutralizing activity were measured against all of the emerging variant spike protein variants tested, Inovio reported, including those first reported in the U.K, South Africa and Brazil – the B.1.1.7, B.1.351 and P.1 Spike peptides, respectively.
The study also showed the T-cell responses induced by INO-4800 vaccination were fully maintained against the U.K., South African and Brazilian variants when compared to the T-cell responses to the original Wuhan strain, Inovio reported.
"Obviously, the successes with the mRNA vaccines, their efficacy and rollout have been phenomenal. But as public health experts have encountered, recently with troubles with the J&J and AZ vaccines, these are not expected," he said. "We really feel that our DNA vaccines have very important positive attributes that would add to our arsenal against this virus, both during the pandemic period and hopefully soon in the endemic periods."
The Plymouth Meeting, Pa.-based company’s vaccine candidate is composed of an optimized DNA plasmid and is delivered directly into cells in the body via electroporation using the company's Cellectra 2000 devices. It has a couple of potential advantages over currently available vaccines. With the capacity to stay stable at room temperature for more than a year and at 37°C for more than a month, it does not need to be frozen during transportation or storage, which should make it easier to distribute far and wide vs. the mRNA-based headliners that require cold chain logistics. Furthermore, the candidate’s safety profile has, so far, appeared supportive of safe readministration if immunity wanes, a feature that could support its use as a seasonal booster without concern for generating an anti-vector response.
As investors digested the new analyses of data from Inovio's phase I study of INO-4800, the phase II segment of the company's phase II/II trial, Innovate, is wrapping up. "We should have the immune responses and safety data from 400 volunteers in the U.S. this quarter," Kim said. The company is also drawing together materials addressing questions that led the FDA to place a partial clinical hold on the program last year. Assuming concurrence from the FDA on the company's plans to move forward, something Kim expressed confidence in, he said he expects the company will start the phase III portion of the study this quarter.
In January, Advaccine Biopharmaceuticals Suzhou Co. Ltd., of Suzhou, China, licensed exclusive rights to develop, manufacture and commercialize INO-4800 within greater China.