CROI 2023 – progress on efforts to cure HIV

Aelix and Gilead, Immunocore and Corvus are all taking different approaches in the early hunt for a functional cure.

Gilead is trying to cure HIV, but it is not the only one. The recent Conference on Retroviruses and Opportunistic Infections (CROI) featured several projects that, it is hoped, could pave the way to a functional cure.

Companies are taking various approaches to hit the HIV reservoir, which is thought to be the key to success, but the work here is early – in some cases, very early indeed.

Therapeutic vaccine

One of the most advanced potential functional cures is a combination of Gilead’s TLR7 agonist vesatolimod with a therapeutic vaccine candidate being developed by Aelix. The HIVACAT T-cell immunogen (HTI) vaccine is designed to elicit an immune response to HIV. While therapeutic vaccines have fallen short in the past, Aelix reckons that it could have found the answer by hitting regions of the virus that are also targeted by patients who naturally control HIV.

Data from the phase 2 Aelix-003 study suggested that patients receiving the vaccine/vesatolimod combo were less likely to experience a rebound in viral load versus those on placebo. This was tested by interrupting antiretroviral therapy for up to 24 weeks; plasma viral load was monitored weekly, and therapy was resumed if viral load went above a predetermined threshold.

Of the 30 vaccine/vesatolimod-treated patients, 33% remained off antiretroviral therapy over 24 weeks, versus 24% of those on placebo. 

Privately held Aelix's chief scientific officer, Christian Brander, conceded that the absolute difference was not as great as in the previous Aelix-002 trial, which tested a more complex HTI vaccine regimen without vesatolimod. However, he put this down to a "number of placebo controls that presented with beneficial host genetics and low reservoir". 

In the 003 trial there was a more pronounced difference in patients with a high viral reservoir at baseline.

Mr Brander said it was too early to comment on whether Aelix would take a vaccine/vesatolimod combo into phase 3. The company is awaiting data from the BCN03 trial, evaluating a T and B-cell vaccine combo, before deciding on future steps.

T-cell receptor

Immunocore is also aiming to harness T cells with its bispecific candidate IMC-M113V, which comprises a T-cell receptor domain and an anti-CD3 effector function. The latter recruits T cells while the former targets a peptide derived from the Gag protein that is presented on the surface of HIV-infected cells; the ultimate goal is redirecting non-exhausted T cells to target and kill the infected cells in the viral reservoir.

Data on this project are still early, with CROI featuring initial phase 1 results from a phase 1/2 study called Strive. In the single-ascending dose portion, 12 patients received IMC-M113V at 1.6µg, 5µg and 15µg.

Immunocore reckons the signs are good: the group pointed to a fourfold or greater increase in IL-6 in five of 10 patients on the highest dose, saying this was a predefined marker of pharmacodynamic activity. The company has started enrolling HIV patients into the multiple-ascending dose portion of the study, with a target of up to 28 patients.

Like Aelix, the group plans to evaluate viral rebound after interruption of antiretroviral therapy. Immunocore hopes a 12-week dosing period could lead to a persistent effect, a company spokesperson told Evaluate Vantage.

ITK inhibitor

Even earlier is the microcap Corvus Pharmaceuticals, which touted preclinical results on its oral interleukin-2-inducible T-cell kinase (ITK) inhibitor CPI-818. Corvus highlighted data from cell models suggesting that the asset could stop the re-emergence of latent HIV.

The company plans to take CPI-818, which is already in phase 1 in T-cell lymphoma, into the clinic in HIV next year – although the group’s chief executive officer, Richard Miller, told Evaluate Vantage that it ultimately hoped to find a partner for the infectious disease.

He believes a short course of CPI-818, “on the order of a few months”, would be required to effect a functional cure. He noted: “ITK is required for the HIV virus to replicate, assemble and infect cells – so there are multiple modes of action”.

There do not appear to be any other ITK inhibitors in active development, according to Evaluate Pharma.

Selected functional cure approaches presented at CROI 2023
Project(s) Company Description Study details
HTI vaccine + vesatolimod Aelix & Gilead Therapeutic vaccine + TLR7 agonist Ph2 Aelix-003: 33% (10/30) treated pts remained off ART for 24wks, vs 24% (4/17) with placebo
IMC-M113V  Immunocore Bispecific soluble T-cell receptor Ph1/2 Strive: SAD portion found rise in IL-6; MAD portion planned
CPI-818 Corvus ITK inhibitor Preclinical; reduction in reversal of viral latency in cell models
TLR7=toll-like receptor 7; ITK=interleukin-2-inducible T-cell kinase; Source: CROI 2023 & company releases.

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