“These data reinforce our view of TMB-365 as a differentiated antibody with potential across multiple long-acting HIV combinations,” said Jimmy Chang, Ph.D., Chief Executive Officer of TaiMed Biologics. “Its host-directed mechanism, antiviral activity and pharmacokinetic profile provide a foundation for exploring combinations with other antibodies and small-molecule antiretrovirals. TMB-365/TMB-380 is our most advanced application of this approach, and the susceptibility findings strengthen the scientific rationale for pairing these two antibodies.”
TMB-365: Clinical activity and a distinct role in future HIV combinations
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 attachment, providing a mechanism distinct from antibodies that target the virus directly. TMB-365 was engineered to improve the breadth of antiviral coverage and pharmacokinetics relative to ibalizumab. TaiMed is developing TMB-365 as a distinct antibody asset for use in combination HIV regimens.
The randomized, placebo-controlled Phase 1 study (NCT04027387) evaluated single intravenous doses of 400, 800 and 1,600 mg in 25 people living with HIV over 10 weeks. The lower-dose cohorts included participants with detectable HIV who were off antiretroviral therapy; the 1,600-mg cohort remained on stable combination antiretroviral therapy with suppressed HIV. Key findings included:
• Antiviral activity: Mean maximum HIV-1 RNA reductions were 1.55 and 1.57 log10 copies/mL at 400 and 800 mg, respectively. Antiviral effects were observed for up to two and four weeks, respectively.
• Tolerability: No serious treatment-emergent adverse events, Grade 3 or higher events, or adverse-event-related discontinuations were observed. All 23 treatment-emergent events were mild or moderate; six events in three participants were considered related to TMB-365. No anti-drug antibodies were observed.
• Target engagement and dosing potential: In a limited subset, mean CD4 receptor occupancy remained at or above 80% for five to six weeks at 800 and 1,600 mg. The pharmacokinetic findings support further evaluation of higher doses and dosing intervals of eight to 12 weeks.
• Resistance observations: No resistance or cross-resistance to TMB-365 or approved entry inhibitors was observed during the study.
Together, these results support continued development of TMB-365 beyond a single antibody pairing. Its host-directed mechanism and engineered properties provide a rationale for exploring combinations with complementary antibodies and long-acting small-molecule antiretrovirals. The safety, efficacy and dosing of such future combinations will require clinical evaluation.
TMB-365/TMB-380: Complementary susceptibility supports combination development
The second presentation reports laboratory susceptibility findings for TMB-365 and TMB-380, a broadly neutralizing antibody that targets the CD4-binding site on the HIV envelope protein gp120. Researchers evaluated a panel of 40 HIV pseudotypes: 20 susceptible to TMB-380 and 20 with reduced susceptibility or resistance to TMB-380. They also studied a laboratory-selected virus resistant to LM52, a precursor of TMB-365.
• TMB-365 retained activity against variants less susceptible to TMB-380: Its geometric mean IC50 was similar in the TMB-380-susceptible and reduced-susceptibility groups: 0.054 and 0.057 micrograms/mL, respectively. Of the 20 variants with reduced susceptibility or resistance to TMB-380, 19 were susceptible to TMB-365; one showed incomplete neutralization, with a maximum inhibition of 70%.
• Complementary activity was also seen in the precursor experiment: The LM52-resistant virus became more susceptible to VRC-07 and VRC-01, antibodies related to TMB-380, supporting the hypothesis that the two mechanisms may cover different viral susceptibility gaps.
These in vitro findings support a complementary-activity hypothesis for TMB-365/TMB-380. Their clinical implications for durable viral suppression and resistance outcomes require further study.
“The Phase 1 findings demonstrate TMB-365's antiviral activity in people living with HIV, while the laboratory study helps explain why its host-directed mechanism could complement a virus-directed antibody,” said Martin Markowitz, M.D., Medical Director of TaiMed Biologics and presenting author of both studies. “TMB-365's activity against variants with reduced susceptibility to TMB-380 is encouraging. Further clinical studies will determine whether that complementarity translates into durable viral suppression and favorable resistance outcomes.”
TMB-365/TMB-380 is being evaluated as an antibody-only maintenance regimen for virologically suppressed people living with HIV. In the earlier 20-participant Phase 2a study, dosing every eight weeks over 24 weeks produced no protocol-defined virologic failures among participants who completed treatment. An ongoing Phase 2b study is evaluating the regimen against continued oral antiretroviral therapy, with interim results expected by year-end 2026.
IDWeek 2026 presentation details
Oral Presentation
Title: Single-dose escalation study of TMB-365 in people living with HIV: safety, pharmacokinetics, and antiviral activity.
Date & Time: Friday, October 23, 2:45-2:57 p.m. ET
Session: Hot Off the Press: New Pathways in HIV Treatment
Location: Room 103 AB
Poster Presentation
Title: TMB-365 and TMB-380: A potentially resistance repellant stand-alone maintenance bNAb regimen in suppressed people living with HIV-1 on combination antiretroviral therapy.
Date & Time: Thursday, October 22, 12:15-1:30 p.m. ET
Session: Resistance Mechanisms”
Location & Poster Code: Poster Hall B-C, Poster P-82
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