Immunocore’s big swing for a functional HIV cure has cleared its first hurdle. No serious adverse events were tied to the British biotech’s bispecific T-cell engager in a phase 1/2 trial, and the investigational treatment also reduced virus levels in the blood of three patients living with HIV.
The data come from 16 patients treated in the dose-escalation portion of the Strive trial, which is still enrolling. Immunocore shared the results in a March 10 release and is presenting the data at the 2025 Conference on Retroviruses and Opportunistic Infections in San Francisco.
Patients received weekly infusions of the antibody—called IMC-M113V—in doses up to 60, 120 or 300 micrograms for 12 weeks. All patients continued their standard antiretroviral treatment while receiving IMC-M113V. After dosing finished, patients paused their antiretrovirals for 12 weeks of monitoring. If a patient's virus levels were measured to be above a certain threshold four times during this period, the patient went back on antiretrovirals.
Five of the six patients receiving the highest dose had a fever caused by mild (grade 1) cytokine release syndrome for about four hours after their first infusion, Immunocore said in the release, but, otherwise, the treatment was well tolerated.
“Safety is really paramount,” Lucy Dorrell, M.D., head of infectious diseases at Immunocore, told Fierce Biotech in an interview.
None of the patients discontinued treatment due to adverse events, but one patient in the 300-microgram group did withdraw from the study before dosing was finished for reasons unrelated to treatment, according to Immunocore.
Though safety is the main focus of the trial, researchers also monitored virus levels in the blood of patients after they’d completed their treatment regimens and gone off antiretrovirals for 12 weeks. Normally, after going off antiretrovirals, HIV levels in the blood go up, so stopping the therapy allowed the researchers to see what effect IMC-M113V had on this rebound.
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The analysis revealed that three patients, one in the 120 microgram group and two in the 300 microgram group, saw their virus levels initially start to rebound before levels suddenly dipped back down.
“It went up a bit and then came down again, which would suggest that the immune system was able to control [it],” Dorrell said. One of the three patients was able to stay off antiretrovirals for the full 12 weeks.
The delayed virus control happened even though there was no longer any IMC-M113V in the patients’ systems, though the reason for this is currently unclear, Dorrell added. It’s possible that the immune system learned to tackle the virus on its own, or that there’s some long-term effect of exposure to the drug.
As the Strive trial continues, Immunocore will test higher doses of IMC-M113V as it works to find a patient-friendly dose that is effective without compromising safety, Dorrell said.
IMC-M113V is a bispecific antibody designed to bind to T cells and cells infected with HIV, spurring the T cells to destroy the infected cells. The goal is to wipe out the reservoir of infected cells, so that patients no longer have any virus in their bodies. Currently, people with HIV need to take antiretrovirals to repress the virus’s activity for the rest of their lives.
HIV-infected cells break down parts of the virus inside them and present these bits on their surfaces for the immune system to monitor, but these virus fragments are “either not very abundant or they're highly variable,” Dorrell said, which makes targeting the HIV reservoir difficult. IMC-M113V is “super sticky and specific,” binding tightly to infected cells while leaving healthy cells alone, she said.
The platform IMC-M113V is built on is the same one underpinning Immunocore's approved drug Kimmtrak, an immunotherapy for patients with a rare form of eye cancer.
Immunocore T-cell engagers bispecific antibodies HIV clinical trial data Kimmtrak Antiretroviral Drugs Clinical Data Research Biotech