French biotech EnnoDC has announced positive long-term data from its Phase I trial evaluating Antibody Mediated Vaccines (AMVs) in HIV, demonstrating durable immune responses that support the company's expansion into oncology applications.
The final results from the ANRS VRI06 Phase I trial (NCT04842682) were presented by Professor Yves Levy at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco on March 13, 2025.
Novel AMV Platform Shows Durable Immunity
The trial evaluated CD40.HIVRI.Env (AMV.HIVRI), a novel immunotherapy that combines the targeted action of an immunomodulatory antibody with the long-lasting effect of a vaccine. This first-in-human study assessed both safety and immunogenicity in non-HIV infected volunteers.
The data demonstrated that CD40.HIVRI.Env induced controlled, durable, and potent immune responses with an excellent safety profile. Most notably, these immune responses persisted for a median of 80 weeks after study entry.
"These data establish a clinical proof-of-concept for AMVs in HIV, demonstrating the ability of our AMV studio to engage, prime and activate Dendritic Cells, in vivo, to drive a highly controlled and sustained immune response," said Prof. Yves Levy, co-founder and Chief Scientific Officer of EnnoDC.
The long-term follow-up evaluated the durability of these responses and the effect of a single new injection (late boost) of CD40.HIVRI.Env, with or without adjuvant. Results showed that even a single boost of low dose, without adjuvant, was sufficient to extend immune responses for an additional six months following the late boost.
AMV Technology Platform
AMVs represent a new class of immunotherapy with a unique mechanism of action. Each AMV consists of two key components:
- A "head" containing a CD40 dendritic cell engager
- A "tail" featuring a commutable antigen from a virus or tumor
This structure enables AMVs to induce specific, controlled, and broad immune responses that mobilize both antibody- and cell-mediated immunity.
Earlier results from the first phase of the ANRS VRI06 trial, published in EClinicalMedicine in 2024, had already shown a favorable safety profile and strong immunogenicity, with responses persisting until week 48 (six months after the last boost).
Expanding into Oncology Applications
Building on these positive results in infectious disease, EnnoDC is now advancing its AMV technology into cancer immunotherapy.
"These compelling results in HIV reinforce our confidence in the AMV platform's unique ability to deliver potent, long-lasting immune responses, making it an ideal candidate for advancing next-generation oncology therapies, particularly in HPV-induced cancers," said Christophe Hubert, CEO of EnnoDC.
The company recently reported encouraging initial clinical data for its oncology AMV candidate CD40.HVac (AMV.HPVE6E7) at the 2024 ESMO Immuno-Oncology Congress. This candidate, currently in a Phase 1/2a trial for HPV-positive oropharyngeal cancer, demonstrated robust HPV-specific CD4+ and CD8+ T cell activation and a favorable safety profile.
Current Oncology Pipeline
EnnoDC's current immuno-oncology pipeline includes:
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AMV.HPVE6E7 (lead candidate): Currently in Phase 1/2a trials for HPV-positive oropharyngeal cancer, showing early signs of tumor regression, strong immunogenicity, and a favorable safety profile.
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AMV.PCA: A next-generation AMV candidate targeting prostate cancer, designed to overcome immune evasion mechanisms that have limited the success of immunotherapy in this indication.
The company positions itself at the forefront of next-generation cancer immunotherapies with its first-in-class approach based on AMVs, combining the specificity of antibodies with the durability of vaccines.
Clinical Trial Details
The ANRS VRI06 trial was the first human clinical trial assessing an AMV targeting the HIV envelope in non-HIV infected volunteers. The abstract presented at CROI 2025 (abstract #426) was titled "Un-adjuvanted CD40.HIVRI.Env vaccine late boost induces durable immune responses: ANRS VRI06 trial" by Yves Levy and colleagues.
With these promising results, EnnoDC is actively engaging investors to accelerate its lead oncology programs to clinical inflection points, leveraging its strong scientific foundation, strategic partnerships, and clear regulatory pathways.
