TaiMed reports Phase 1 data showing up to a 1.57-log reduction in HIV-1 RNA with TMB-365, alongside laboratory findings supporting antibody combination research.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
TaiMed Biologics reported new clinical and laboratory findings on October 21, 2026, highlighting the antiviral activity of TMB-365 and its potential role in long-acting HIV treatment combinations. The data, scheduled for presentation at IDWeek 2026 in Washington, D.C., include Phase 1 results and laboratory experiments evaluating TMB-365 against HIV variants with reduced susceptibility or resistance to TMB-380.
The findings support continued development of antibody-based approaches intended to maintain HIV suppression with less frequent administration. However, the clinical results concern single-dose TMB-365, while the susceptibility findings provide laboratory evidence relevant to the combination. Neither establishes the long-term efficacy of the proposed antibody-only regimen.
TMB-365 Targets the Host-Cell CD4 Receptor
TMB-365 is an investigational, second-generation monoclonal antibody derived from ibalizumab. It binds domain 2 of the CD4 receptor on host cells and inhibits HIV entry after viral attachment. This host-directed mechanism differs from that of antibodies targeting viral proteins directly.
TaiMed engineered TMB-365 to improve antiviral coverage and pharmacokinetic properties relative to ibalizumab. The company is evaluating it as a component of long-acting regimens involving other antibodies and small-molecule antiretrovirals.
Phase 1 Study Demonstrates Antiviral Activity
The randomized, placebo-controlled Phase 1 study (NCT04027387) enrolled 25 people living with HIV and evaluated single intravenous doses of 400, 800 and 1,600 mg over 10 weeks. Participants in the lower-dose cohorts had detectable HIV and were not receiving antiretroviral therapy, whereas those in the 1,600 mg cohort were receiving stable combination antiretroviral therapy with suppressed viral loads.
Mean maximum reductions in HIV-1 RNA reached 1.55 log₁₀ copies/mL at 400 mg and 1.57 log₁₀ copies/mL at 800 mg. Antiviral effects were observed for up to two and four weeks, respectively. These findings demonstrate short-term antiviral activity, but the study does not establish sustained suppression with repeated dosing.
The initial safety findings were also encouraging. No serious treatment-emergent adverse events, Grade 3 or higher adverse events, or adverse-event-related treatment discontinuations were reported. All 23 treatment-emergent adverse events were mild or moderate, with six events in three participants considered related to TMB-365. No anti-drug antibodies were detected.
Target Engagement Informs Longer Dosing Intervals
Mean CD4 receptor occupancy remained at or above 80% for five to six weeks in a subset of participants receiving 800 mg or 1,600 mg. These pharmacodynamic findings support further evaluation of longer dosing intervals, including eight to 12 weeks.
However, receptor occupancy indicates target engagement rather than sustained viral suppression. The proposed intervals remain investigational and require clinical validation. No resistance or cross-resistance to TMB-365 or approved entry inhibitors was observed during the study period, although the single-dose design limits conclusions about longer-term resistance.
Laboratory Results Support the TMB-365/TMB-380 Combination
TaiMed also evaluated TMB-365 against 40 HIV pseudotypes, including 20 susceptible to TMB-380 and 20 with reduced susceptibility or resistance to the antibody. TMB-380 is a broadly neutralizing antibody that targets the CD4-binding site on the HIV envelope protein gp120.
TMB-365 retained activity across both groups, with geometric mean IC₅₀ values of 0.054 µg/mL among TMB-380-susceptible variants and 0.057 µg/mL among variants with reduced susceptibility or resistance. Nineteen of the 20 less-susceptible variants remained susceptible to TMB-365. One showed incomplete neutralization, with maximum inhibition of 70%.
Additional laboratory experiments found that a virus selected for resistance to LM52, a precursor of TMB-365, became more susceptible to VRC-07 and VRC-01, antibodies related to TMB-380. Together, these results support the hypothesis that the antibodies could provide complementary activity against different viral susceptibility profiles. They do not demonstrate that the combination will prevent resistance or maintain viral suppression in clinical practice.
Phase 2 Studies Will Test Clinical Relevance
In an earlier Phase 2a study involving 20 participants, the TMB-365/TMB-380 combination was administered every eight weeks over 24 weeks. TaiMed reported that 94% maintained HIV-1 RNA below 50 copies/mL through Week 24, with no protocol-defined virologic failures among participants who completed treatment.
The ongoing Phase 2b study is evaluating the combination against continued daily oral antiretroviral therapy in virologically suppressed adults. The company’s program information describes a 48-week study involving 83 participants, with enrollment completed in May 2026. Interim results are expected by the end of 2026.
The FDA granted the combination Fast Track Designation in 2024. TMB-365/TMB-380 remains investigational and has not been approved by the FDA or other regulatory authorities.
Clinical Interpretation
TMB-365 demonstrated measurable short-term antiviral activity and an initial tolerability profile that supports further investigation. The laboratory findings strengthen the scientific rationale for combining its host-directed mechanism with TMB-380, while the Phase 2a results provide preliminary clinical evidence for the dual-antibody approach.
The key question is whether the combination can maintain viral suppression with acceptable safety over longer treatment periods. Results from the ongoing Phase 2b study will help determine whether the laboratory evidence and early clinical findings translate into a viable maintenance option for people living with HIV.
References
TaiMed Biologics Reports IDWeek 2026 Data Highlighting TMB-365 and Its Potential Across Long-Acting HIV Combinations, TaiMed Biologics, 21 October 2026
Dose Escalation Safety Study of TMB-365 in HIV-1 Infected Participants, ClinicalTrials.gov ID NCT04027387
TMB-365 and TMB-380 in Suppressed HIV-1 Infected Individuals, ClinicalTrials.gov ID NCT05275998
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.