TMB-365 is a long-acting, CD4-directed monoclonal antibody targeting a host receptor required for HIV entry, while TMB-380 is a long-acting broadly neutralizing antibody targeting the CD4-binding site of HIV-1 gp120. The publication, titled “Safety, pharmacokinetics, and antiviral activity of a combination of TMB-365 and TMB-380 in people living with HIV suppressed with antiretroviral therapy in the USA: a phase 1b/2a, open-label, dose-escalation study,” reports safety, pharmacokinetic and antiviral activity results supporting continued clinical development of the dual-antibody regimen.
In the Phase 2a portion of the study, participants discontinued oral ART and received 4,800 mg each of TMB-365 and TMB-380 intravenously every eight weeks for 24 weeks. The study was conducted without pretreatment susceptibility screening for either antibody. Among 17 participants with Week 24 data included in the per-protocol analysis, 16 (94%) maintained HIV-1 RNA below 50 copies/mL. In the intention-to-treat population, 16 of 20 participants (80%) were suppressed at Week 24. No participant met the protocol-defined criteria for confirmed virologic failure.
“This publication provides important peer-reviewed validation of the scientific foundation behind TMB-365/TMB-380 and strengthens our conviction in the potential of a differentiated, antibody-based approach to long-term HIV treatment,” said Jimmy Chang, Ph.D., Chief Executive Officer of TaiMed Biologics. “As people with HIV live longer and increasingly manage multiple chronic conditions and medications, we believe the next generation of long-acting therapies will need to address more than dosing frequency alone. Our goal is to develop an approach that combines durable viral suppression with broad applicability, treatment flexibility and a profile suited to the realities of lifelong HIV care.”
Treatment-emergent adverse events in the Phase 2a study were mild or moderate, with no serious treatment-emergent adverse events, deaths, Grade 3 or 4 treatment-emergent adverse events, opportunistic infections or acute infusion reactions reported. Mean CD4 cell counts remained stable throughout the study without evidence of depletion.
Pharmacokinetic results supported administration every eight weeks and provided insights that have informed subsequent clinical development. Three participants experienced transient HIV-1 RNA elevations of approximately 200–300 copies/mL followed by re-suppression. These participants had body weights above 90 kg and lower TMB-365 exposures. Exploratory analyses identified body weight as a covariate of TMB-365 exposure, supporting the incorporation of bodyweight-based TMB-365 dosing into the subsequent Phase 2b study.
“The ability to maintain viral suppression in most participants for 24 weeks with a complete antibody regimen is encouraging, particularly given that participants were enrolled without pretreatment susceptibility screening,” said Martin Markowitz, M.D., Medical Director of TaiMed Biologics and lead author of the publication. “The ongoing Phase 2b study is designed to build on these findings in a larger population and provide a more rigorous assessment of the regimen’s potential as long-acting maintenance therapy.”
The study also found improvements in selected measures of treatment satisfaction during TMB-365/TMB-380 treatment, including convenience, flexibility, fit with lifestyle and willingness to recommend the treatment to others.
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