Inovio Pharmaceuticals Inc (INO)

[Lakers_w]

Version 2, 1/25/22 This report provides results for the expansion of a Phase 1 trial to include older and elderly participants and an optional booster dose with the aim to evaluate the safety, tolerability, and immunogenicity of INO-4800, a SARS-CoV-2 vaccine encoding the S protein[14], including the immune responses 6 months following dose 2 and 2 weeks following the optional booster dose.

INO-4800 appeared to be well-tolerated at all three dose levels, with no treatment-related serious adverse events (SAEs) reported. Most AEs were mild in severity and did not increase in frequency with age and subsequent dosing. These results are consistent with the severity of AEs and lack of treatment-related SAEs observed in the U.S. Phase 2 trial comparing the 1.0 mg and 2.0 mg doses of INO-4800 in approximately 400 subjects[15] and those studies conducted outside the U.S. by Inovio collaborators (International Vaccine Institute, Advaccine – manuscripts in preparation). The lower frequency of treatment-related AEs reported by older and elderly participants in our study is consistent with findings of other studies evaluating SARS-CoV-2 vaccines[19, 20]. Weaker inflammatory reactions consequent to immunosenescence may explain the lower incidence of AEs among elderly participants[21, 22].

Induction of both humoral and cellular responses were observed across all three dose groups, inclusive of binding and neutralizing antibodies and cytokine producing T cells as well as exhibiting lytic potential. Immunization with the 2.0 mg dose resulted in the highest GMTs of neutralizing and binding antibodies as well as the highest magnitudes of IFN? production to SARS-CoV-2 of any dose in all age groups tested, and the increases in antibody levels were statistically significant above baseline at 6 months following dose 2. Importantly, increases in both humoral and cellular immune responses were statistically significant following the booster dose.

The contribution of the CD8+T cell response to vaccine efficacy has become increasingly recognized as they have been detected early after vaccination[23] and due to their role in controlling infection[24, 25]. Specifically, it has been established that CD8+T cells expressing cytokines such as IFN? and TNFa as well as markers involved in activation status and proliferation such as CD38 and Ki67 contribute to limiting disease severity during SARS-CoV-2 infection[24]. Additional studies have identified the expression of CD69 and CD137 on SARS-CoV-2 specific CD8+T cells being associated with less severe disease[25]. This expanded Phase 1 trial demonstrates that immunization with INO-4800 induces SARS-CoV-2 specific CD8+T cells exhibiting these specific characteristics, suggesting the induction of a vaccine-induced cellular response that has potential to protect against severe COVID-19. As VoCs continue to emerge, the generation of cross-reactive activated CD8+T cells with lytic potential is likely to play an important role in preventing severe disease. We have previously demonstrated that vaccination with INO-4800 induces T cells and neutralizing antibodies that are active against the parental SARS-CoV-2 strain as well as the B.1.1.7, B.1.351, and P.1 VoCs[26].

This trial demonstrated that immune responses elicited by a 2-dose primary series of INO-4800 could be boosted by a third dose without safety or tolerability concerns and positions INO-4800 as an important candidate for continued development as a stand-alone SARS-CoV-2 vaccine, as well as for continued examination in combination approaches. The potential ability to administer INO-4800 multiple times, with high tolerability, along with its ease of scalability and thermostability, contribute to its potential value in combatting the COVID-19 pandemic.

https://www.medrxiv.org/content/10.1101/2021.10.06.21264584v2.full