8-K: Immunocore Presents Promising Initial Data for HIV Functional Cure Candidate IMC-M113V at CROI 2025

Immunocore's IMC-M113V shows promising initial data in HIV patients, demonstrating good tolerability and signals of dose-dependent viral control after antiretroviral treatment interruption.

Summary

• Immunocore presented initial data from the Phase 1/2 STRIVE trial of IMC-M113V, a functional cure candidate for HIV, at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025.
• The data shows that IMC-M113V was well tolerated and exhibited signals of dose-dependent viral control after antiretroviral treatment (ART) was interrupted.
• The trial included 16 people living with HIV (PLWH) who were stable on ART, with three sequential cohorts receiving weekly IV infusions of IMC-M113V at doses up to 300 mcg over 12 weeks, followed by analytical treatment interruption (ATI) for up to 12 weeks.
• All doses were well tolerated, and no serious adverse events (AEs) or dose-limiting toxicities were observed.
• In the 15 evaluable PLWH, delayed viral rebound and/or viremia control at any point during ATI was observed in 0 of 5 PLWH at 60 mcg, 1 of 5 at 120 mcg, and 2 of 5 at 300 mcg.
• The 3 PLWH with evidence of viral control had a viral load of approximately 200 c/mL at week 8, compared to a historical rate of 5%.
• Two of these three PLWH remained off ART for the entire 12-week ATI period.
• There was also a reduction in CD4+ T cell-associated HIV Gag RNA in some PLWH during treatment, indicating a reduction in the active virus reservoir.
• A trend of reduction in intact HIV DNA was also observed post-treatment in a preliminary analysis of 6 people treated at the two highest doses.

Sentiment

Score: 7

Explanation: The document presents promising initial data for IMC-M113V, with good tolerability and signals of viral control. However, it is still early-stage data, and further studies are needed to confirm the efficacy and safety of the drug. The sentiment is cautiously optimistic.

Positives

• IMC-M113V demonstrates a favorable safety profile in the initial MAD data.
• The drug shows signals of dose-dependent anti-viral activity.
• Some participants were able to interrupt ART for 12 weeks or longer, which is uncommon.
• There was a reduction in the active virus reservoir in some participants.
• A trend of reduction in intact HIV DNA was observed post-treatment.

Negatives

• Mild cytokine release syndrome (fever) was observed in five of the six participants in the 300 mcg cohort.
• Viral control was only observed in a subset of participants (3 out of 15 evaluable PLWH).
• The viral load in the 3 PLWH with evidence of viral control was approximately 200 c/mL at week 8, indicating that the virus was not completely suppressed.

Risks

• The trial is still in its early stages (Phase 1/2), and further data is needed to confirm the efficacy and safety of IMC-M113V.
• The observed viral control was not consistent across all participants.
• The long-term effects of IMC-M113V on HIV viral reservoir and immune response are not yet known.
• The company's ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products is a risk.
• The company's ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK, is a risk.

Future Outlook

The MAD portion of the STRIVE trial continues and is evaluating higher doses, to be followed by expansion cohorts at one or more doses. Immunocore aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission.

Management Comments

• Dr. Beatriz Mothe stated that she is encouraged by the safety profile and initial signals of anti-viral activity of IMC-M113V in the Phase 1/2 trial.
• Dr. Mothe also mentioned that it is uncommon to be able to interrupt ART for 12 weeks or longer, with the vast majority of people showing viral rebound by 4 weeks.

Industry Context

The development of IMC-M113V represents a novel approach to HIV treatment, focusing on achieving a functional cure by targeting the HIV reservoir. This aligns with the broader industry trend of developing immunotherapies for infectious diseases. Competitors are also exploring various strategies to achieve HIV remission or cure, including gene editing, therapeutic vaccines, and other immunomodulatory approaches.

Comparison to Industry Standards

• The observation of viral control in some patients after ART interruption is a promising signal, especially considering the historical rate of 5% for this observation.
• The fact that two patients remained off ART for the entire 12-week ATI period is also notable, as this is a challenging goal in HIV treatment.
• Gilead Sciences is developing long-acting HIV treatments and exploring curative strategies.
• ViiV Healthcare is focused on developing new antiretroviral therapies and exploring immune-based approaches.
• The observed reduction in CD4+ T cell-associated HIV Gag RNA and the trend of reduction in intact HIV DNA are encouraging signs that IMC-M113V may be impacting the HIV reservoir.

Stakeholder Impact

• Positive impact on patients living with HIV, as IMC-M113V has the potential to provide a functional cure.
• Potential positive impact on shareholders, as the promising data could increase the value of Immunocore.
• Positive impact on the medical community, as IMC-M113V represents a novel approach to HIV treatment.

Next Steps

• Enrollment in the MAD portion of the trial continues with higher doses being evaluated.
• Expansion cohorts at one or more doses will be evaluated.
• Further data from the trial at higher doses will be presented.

Key Dates