BioNTech SE has launched a first-in-human (FIH) Phase I clinical trial (NCT07392372) to evaluate the safety, pharmacokinetics, and antiviral activity of BNT351, an investigational broadly neutralizing antibody (bNAb). The study represents a strategic expansion of BioNTech’s infectious disease pipeline, applying its immunotherapy expertise to address the persistent challenge of chronic HIV-1 infection in both HIV-negative adults and people living with HIV (PLWH).
Trial specifics
The study is a Phase I, randomized, multi-part trial designed to assess the safety and biological activity of BNT351. The protocol is divided into two distinct segments:
Part A (Dose Escalation): A randomized, double-blind, placebo-controlled study in adults living without HIV. This segment will evaluate a single ascending dose (SAD) across four cohorts (A1–A4). Cohort A1 will utilize subcutaneous (SC) administration, while Cohorts A2 through A4 will utilize intravenous (IV) infusion.
Part B (Proof-of-Concept): An open-label, single-dose study in adults living with HIV (PLWH) who have detectable viral levels. This part will evaluate the antibody’s direct antiviral activity and its impact on HIV viral load over an 8-week observation period before participants resume combination antiretroviral therapy (cART).
The trial intends to enroll approximately 60 participants with an age range of 18 to 65 years. Participants must meet strict eligibility criteria, including a low likelihood of HIV acquisition for the Phase Ia healthy volunteer cohorts and confirmed HIV-1 infection for the Phase Ib cohort.
As a Phase I FIH study, the primary endpoints are focused on the safety and tolerability of BNT351, specifically the frequency and severity of treatment-emergent adverse events (TEAEs). Secondary objectives include characterizing the pharmacokinetic (PK) profile—measuring the concentration of BNT351 in the blood over time—and assessing the decline in HIV-1 RNA levels in the Part B cohort. The study, which began in Q1 2026, has an estimated primary completion date of June 2027.
Scientific and industry context
BNT351 is a broadly neutralizing antibody designed to target conserved regions of the HIV-1 envelope glycoprotein, aiming to neutralize a wide array of viral variants. The biological rationale for bNAbs in HIV management is twofold: they can directly neutralize free virions and potentially mediate the killing of infected cells through Fc-effector functions. This approach is being researched as a potential component of long-acting treatment regimens or “shock and kill” cure strategies.
While BioNTech is globally recognized for its mRNA platform, the development of BNT351 highlights the company’s broader “immune engineer” identity, utilizing protein-based modalities alongside its established vaccine technology. This program follows BioNTech’s historical success in infectious diseases with the BNT162b2 COVID-19 vaccine and its ongoing efforts in tuberculosis and malaria.
The initiation of the BNT351 trial joins a competitive landscape of next-generation HIV therapies focused on reducing the burden of daily oral medication. Mepolizumab’s developer, BioNTech, enters a field currently explored by major players like Gilead Sciences and GSK/ViiV Healthcare, both of which are advancing long-acting bNAbs such as lenacapavir and VH3739937 (N6LS).
The BNT351 program is a global first for BioNTech in the HIV space, situating the company among a small group of innovators attempting to move beyond traditional cART toward antibody-mediated viral control.