AELIX Therapeutics S.L., a clinical-stage biotechnology company specializing in the discovery and development of immunotherapies for HIV infection, has announced positive topline results from its AELIX-003 trial.
The study evaluated the safety, tolerability, immunogenicity and efficacy of AELIX Therapeutics’ HTI T-cell therapeutic HIV vaccine in combination with Gilead’s investigational Toll-Like Receptor 7 (TLR7) agonist, vesatolimod (VES), in people with HIV on antiretroviral therapy. VES is an immune modulator being evaluated as part of an investigational combination regimen that could potentially lead to viral remission.
The results were presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI).
About Aelix Therapeutics’ study
The study met its primary and secondary endpoints for safety, tolerability and immunogenicity. The trial also evaluated the efficacy of HTI vaccines in combination with VES to avoid, delay or contain viral rebound compared to a placebo group. For this evaluation, participants underwent an analytical treatment interruption (ATI) in their antiretroviral therapy (ART) for up to 24 weeks. During this time, plasma viral load was monitored weekly.
The data showed that a higher proportion of HTI+VES-treated participants remained off ART for the full 24 weeks. The combination of the HTI vaccine and VES as part of an HIV cure strategy in early treated people with HIV was safe and well tolerated.
Preliminary immune data suggest that HTI vaccines given in combination with VES induce high levels of HTI-specific T-cell responses. VES consistently induced pharmacodynamic response over multiple doses in combination therapy with the HTI vaccine. A lower pre-intervention reservoir was associated with better viral outcomes during the ATI, but only in the placebo group. The magnitude and breadth of vaccine response correlated with better viral outcomes.
HTI vaccines were highly immunogenic in a simpler regimen than in previous AELIX-002 study, and the vaccine-induced responses were associated with higher time off ART, supporting the contribution of the HTI vaccines to better viral control.
‘Important step towards HIV eradication’
“These encouraging efficacy data demonstrate that the HTI vaccine in combination with VES may be able to modulate an individual’s HIV-specific immune response in a way that can potentially contribute to a better HIV control in the absence of ongoing ART. The AELIX-003 data are exciting, and confirm what we have seen in the AELIX-002 study, where the HTI vaccine alone also extended the time off ART for the vaccinated participants,” said Christian Brander, chief scientific officer of AELIX Therapeutics.
“The HTI vaccine is aimed at refocusing the immune response to especially vulnerable sites in HIV. The vaccine contains antigenic regions of HIV that are more commonly targeted by individuals who naturally control the virus. Maintenance of viral remission without ART represents the next frontier in HIV infection treatment and an important step towards HIV eradication.”
About the HTI immunogen
The HTI immunogen was designed at IrsiCaixa by Christian Brander, CSO at AELIX Therapeutics and head of the IrsiCaixa Host Genetics and Cellular Immunity Group, and his colleagues.
It is based on the observation that T-cell responses to certain parts of HIV are enriched in individuals with a non-progressor clinical phenotype. The HTI immunogen combines these regions in a vaccine immunogen. The HTI sequence design is driven by functional immune data from close to 1,000 individuals from four different cohorts on three continents (Mothe et al. 2011).
It does not rely solely on sequence conservation, density of HLA binding motifs or gene expression levels and kinetics as other vaccine candidates do. The predictive power of HTI directed T-cell responses on in vivo virus control has been validated in unrelated cohorts and through sub-studies in samples from earlier vaccine trials, including the STEP trial.