Benzinga | Nov 29, 2021 07:07AM EST

The Omicron Variant Of SARS-CoV-2 Has Minimal Impact On The T Cell Epitopes Contained Within Gritstone's Self-Amplifying mRNA COVID-19 Vaccines

Gritstone bio, Inc. (NASDAQ:GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, today announced that the SARS-CoV-2 T cell epitopes (TCEs) administered within its self-amplifying mRNA (SAM) COVID-19 vaccines are minimally impacted by mutations found within the Omicron (B.1.1.529) variant, reinforcing the platform's potential to address emerging variants of concern.

The recently described Omicron variant, first identified in South Africa on November 9, 2021, was designated a Variant of Concern (VOC) by the World Health Organization (WHO) on November 26, 2021. Early evidence suggests that Omicron carries an increased risk of re-infection, and sequence analysis has revealed many mutations in Spike, including both the N terminal domain (NTD) and receptor binding domain (RBD), which may reduce clinical effectiveness of existing vaccines and/or therapeutic antibodies.

Gritstone's CORAL program is a second-generation SARS-CoV-2 vaccine platform delivering a stabilized Spike protein and highly conserved TCEs derived from other SARS-CoV-2 viral genes, offering the potential for more durable protection and broader immunity against SARS-CoV-2 variants. Delivery vectors can comprise self-amplifying mRNA (SAM), a chimpanzee adenovirus (ChAd), or both (mix-and-match).

Sequence analysis suggests that Gritstone's TCEs are minimally impacted by Omicron. Specifically, of the 146 non-Spike TCE delivered within Gritstone's vaccine currently in clinical trials in the UK and US, only 3 (~2%) are impacted by Omicron. Similar minimal impact of Omicron is observed in two new vaccine TCE constructs expected to enter clinical trials in South Africa before year end.

"Our value proposition in immunotherapy has always centered around two core pillars -- cutting-edge TCE identification and delivering potent vaccines that can elicit strong, broad, and durable immune responses," said Andrew Allen, MD, PhD, Gritstone's Chief Executive Officer. "Strong neutralizing antibody responses to Spike-based vaccines have been shown to be highly protective against COVID-19. However, the possibility of substantial viral resistance arising from Spike mutations has always been present, and Omicron may represent the embodiment of this threat. While engineering an Omicron form of Spike is achievable, it is clearly ideal to both address novel Spike variants and also reduce the likelihood of further variants arising, by delivering a coordinated immune attack against both Spike and other more conserved SARS-CoV-2 genes. This is the path Gritstone has followed to date. With our trial in South Africa scheduled to begin imminently and initial clinical data from our UK trial expected in early 2022, we look forward to unlocking the immense potential of this platform."