Gritstone bio, Inc. announced positive Phase 1 clinical data from the first cohort (10 µg dose of CORAL self-amplifying mRNA (samRNA) vaccine) of its CORAL-BOOST study, demonstrating both strong neutralizing antibody responses to Spike and robust CD8+ T cell responses. Recognizing the increased focus on T cell immunity as a key source of protection against current and future Spike variants, Gritstone's CORAL program is developing a second-generation COVID-19 vaccine designed to drive both robust neutralizing antibodies and induce broad CD8+ T cell immunity. CORAL-BOOST, one of four trials in the company's CORAL program, is evaluating the safety, reactogenicity, and immunogenicity of a samRNA vaccine directed against Spike and highly conserved non-Spike T cell epitopes (TCE) as a booster against SARS-CoV-2 in healthy adults =60 years (n=20 at two dose levels) who previously received two doses of AstraZeneca's first-generation COVID-19 vaccine AZD1222 (Vaxzevria).

Results from First Cohort: A single 10 µg dose of the CORAL program's samRNA vaccine administered to healthy adults =60 years (n=10) at least 22 weeks after two-dose series of Vaxzevria induced: New CD8+ T cell responses across a wide set of non-spike epitopes, including many validated T cell targets in convalescent individuals, demonstrating the potential for variant-proof immunity. Proportion of responses to TCE targets assessed by ELISpot: 36% Nucleoprotein (N), 22% Membrane (M) and 42% ORF3a. A boost to pre-existing T cell responses to Spike epitopes believed to be additive to antibody-based clinical protection conferred by Spike-dedicated vaccines: 120 at peak treatment day vs.

55 at pre-boost (Spot-forming units per 106 cells; assessed by IFNy ELISpot). Broad and potent neutralizing antibodies against SARS-CoV-2 Spike protein, at levels consistent with published data from higher doses of first-generation mRNA vaccines in a similar clinical context (COV-BOOST study; Munro et al., Lancet 2021). 2,370 Geomean ID50 titer values observed at day 29 against Wild Type variant vs.

108 at treatment day 1 (approx. 20-fold increase), 503 Geomean ID50 titer values observed at day 29 against Beta variant vs. 50 at treatment day 1 (approx.

10-fold increase) and 525 Geomean ID50 titer values observed at day 29 against Delta variant vs. 69 at treatment day 1 (approx. 8-fold increase) CORAL's samRNA vaccine was well-tolerated and demonstrated a favorable safety profile with no grade 3/4 adverse events or unexpected reactogenicity or safety events in ten healthy adults =60 years.

The CORAL-BOOST Phase 1 study is ongoing in the United Kingdom and has now dose escalated as planned to a 30 mg dose. Based on these positive Phase 1 data, Gritstone is amending this trial to increase enrollment to 120 subjects and evaluate the addition of a second samRNA-Spike-TCE dose, potentially enabling more rapid advancement into a pivotal study. Immunogenicity and reactogenicity data for additional cohorts is anticipated in coming months.