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Product Development

Arcturus undeterred by low neutralizing titers from COVID vaccine in Phase I; shares slide

Dec 29, 2020 | 2:40 AM GMT

Arcturus believes cellular responses induced by its COVID-19 vaccine candidate will compensate for the underwhelming neutralizing antibody levels in its interim Phase I/II data.

The RNA company’s shares fell 39% after hours Monday, and on Tuesday sank by 54% to $42.36  as investors further digested the data and Wall Street analysts downgraded the stock.

Arcturus Therapeutics Holdings Inc. (NASDAQ:ARCT) reported late Monday that all subjects receiving prime-boost administration of 5 µg ARCT-021 had detectable neutralizing antibodies. But the mean peak titer after boost (46) was not markedly higher than the titer in volunteers who received only one 5 µg injection (32). The mean peak titer in individuals who received a single dose of 7.5 µg vaccine was 33. 

The titers fell on the low end of the range of 12 to 1818 in convalescent sera from patients asymptomatic to severe COVID-19. 

On a conference call to discuss the readout, Arcturus Chief Development Officer Steve Hughes presented data showing that single and prime-boost vaccinations of the company’s self-replicating mRNA vaccine stimulated CD4+ and CD8+ T cell responses in the study.

Eng Eong Ooi, a member of Arcturus’ vaccine platform SAB, hypothesized the robust T cell responses were behind the low antibody production following the second 5 µg ARCT-021 administration. Speaking on the call, Ooi, a Duke-NUS Medical School professor, said the T cell responses may have been too fast for the candidate to boost the humoral response. 

The study enrolled a total of 106 volunteers, including 37 adults ages ≤ 55 years and 29 over 55 whose immunogenicity responses were reported in Monday’s presentation.

The company plans to test single and prime-boost administration of the candidate at the 7.5 μg dose and prime-boost immunization at the lower dose in a Phase II study in about 600 people. The Phase I/II trial does not have a 7.5 μg prime-boost cohort.

Interim Phase II data are expected early next year, with Phase III testing to begin in 2Q21.

Also on the call, President and CEO Joseph Payne noted the company’s data demonstrating protection in animals models, including non-human primates with deficient humoral immunity. He said, “I think that there’s a reasonable sense of optimism that our single administration could be efficacious based on the data that we’ve collected.”

After Hughes’ presentation, Ooi showed animal data that he said suggested that antibodies were not necessary for protection against SARS-CoV-2. He also cited anecdotal reports of recovery in COVID-19 patients with genetic B cell deficiencies.

Ooi added that non-neutralizing antibodies against the spike could mediate protection by stimulating other immune responses such as complement and phagocytosis.

He also cited efficacy data from pivotal trials of two recently authorized mRNA vaccines that showed disease prevention manifested about two weeks after a single vaccination.

Phase I data for mRNA-1273 from Moderna Inc. (NASDAQ:MRNA) and NIH and Comirnaty (BNT162b2) from BioNTech SE (NASDAQ:BNTX) and Pfizer Inc. (NYSE:PFE) showed that neutralizing antibody levels were undetectable in a large proportion of participants before vaccine boost at weeks four and three, respectively. Mean titers in both trials’ subjects rose over 10-fold after a second shot.

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