Immunocore Reports Some PWH Achieve Viral Control and Dose-Dependent Active HIV Reservoir Reduction in IMC-M113V Trial
David Berman, MD, PhD, discusses signs of dose-dependent viral control and reduction in active HIV reservoir in Phase 1/2 STRIVE trial data.
Immunocore Holdings plc presented early findings from the multiple ascending dose (MAD) phase of its Phase 1/2 STRIVE trial for IMC-M113V at CROI 2025 in San Francisco, California. The data suggest that IMC-M113V, a T-cell receptor bispecific therapy, is well tolerated and demonstrates signs of dose-dependent viral control after antiretroviral treatment (ART) interruption.
The trial included 16 participants living with HIV (PLWH) who were stable on ART. David Berman, MD, PhD, executive vice president of research and development at Immunocore, explained the significance of the study, stating, “Our platform is essentially, we create these off-the-shelf, soluble bispecific proteins, where you have a targeting end to target a specific cell, and then the other end is an effector, which brings T-cells close to the target cell, so close that it actually can kill the target cell. So it acts as a bridge.”
No serious adverse events were observed, and mild cytokine release syndrome (CRS) was noted in some participants at higher doses. The highest dose cohort (300 mcg) showed a dose-dependent increase in T-cell-derived cytokines. “With our cancer programs, we see evidence that you're activating T-cells. So when T-cells get activated, you see cytokines being released in the blood, and that leads to something called cytokine release syndrome. So it's fully expected, and essentially that is typically begins with fever,” Berman explained. “Now with repeated dosing, it doesn't appear to be any other adverse event, so it is very well tolerated.”
Three participants showed delayed viral rebound and subsequent viral control during ART interruption. Viral load in these individuals decreased to approximately 200 copies/mL, a result not commonly seen in untreated PLWH. The trial’s aim is to assess IMC-M113V’s ability to reduce the HIV reservoir and control viral replication after ART interruption. Berman commented, “What we saw, quite remarkably, is a dose-dependent evidence of antiviral reduction, and that's manifest as three of these people living with HIV during the ATI had an increase in their virus initially, and then it seems like the immune system was activated and the virus came under control, and the virus went back down to around 200 copies per million.”
The initial results also show a reduction in CD4+ T-cell-associated HIV Gag RNA in some participants, suggesting a reduction in the active viral reservoir. Berman explained the importance of targeting the viral reservoir, “The viral reservoir, as you point out, was the first measure. And there, it's important to remember that a majority of the viral and the analog I give is the iceberg. If you think of the iceberg, only the tip of the iceberg above the water, the tip of the viral reservoir will actually produce replication competent virus.”
Preliminary data also indicate a trend toward reduced intact HIV DNA in patients treated at the two highest doses. IMC-M113V works by targeting an HLA-A*02:01-Gag complex on HIV-infected cells, using an anti-CD3 effector to recruit T-cells that destroy HIV-infected CD4+ cells. Berman elaborated on how the therapy targets HIV, stating, “We identified a protein in HIV called gag that is chopped up inside the cell, and small peptides are presented on the surface by HLA, and we developed the targeting end of the bispecific to recognize that gag peptide.”
The trial is continuing with higher doses being evaluated, and additional expansion cohorts are planned. Berman emphasized that while the results are promising, further investigation is needed: “We need to continue dose escalating, and then we can, you know, correlate that with clinical outcome.”
The next steps for the treatment involve evaluating the antiviral activity of IMC-M113V in larger cohorts, focusing on correlating the reduction in the viral reservoir with clinical outcomes. Berman noted, “The immediate next steps for us is to continue dose escalating, because if we can, it’s very well tolerated with higher doses, we may even see further reductions. And then we would want to look at correlations between the reservoir reduction and antiviral activity.”
As the trial continues, Immunocore is working to determine whether the antiviral activity can be sustained beyond 12 weeks, with the ultimate goal of achieving a functional cure. “The goal here is functional cure. It's not a 12-week interruption of the treatment,” Berman said. “We wanted to go to the harder population, because you can see a signal. So everyone in our trial started ART later, they're less likely to spontaneously control."
