TaiMed’s Anti-CD4 Antibody TMB-365 Reduces HIV Viral Load in Phase 1, Supporting Long-Acting Combination Regimens

TaiMed Biologics’ second-generation anti-CD4 monoclonal antibody TMB-365 reduced HIV-1 viral load and showed no resistance in a phase 1 study in people living with HIV, according to data the company will present at IDWeek 2026.¹ The company said receptor occupancy results support evaluating dosing intervals of 8 to 12 weeks, as it develops TMB-365 as a backbone for long-acting HIV combination regimens.¹

“These data reinforce our view of TMB-365 as a differentiated antibody with potential across multiple long-acting HIV combinations,” said Jimmy Chang, PhD, chief executive officer of TaiMed Biologics.¹

How does TMB-365 work?

TMB-365 is derived from ibalizumab and binds domain 2 of the CD4 receptor on host T cells, blocking HIV entry after the virus attaches.¹ Because it targets a host receptor rather than the virus itself, TMB-365 acts through a different mechanism than antibodies that bind HIV directly.¹ According to TaiMed, it was engineered for broader antiviral coverage and improved pharmacokinetics compared with ibalizumab.¹

Ibalizumab, marketed as Trogarzo, was approved by FDA in March 2018 for people with HIV who have limited treatment options because of extensive prior treatment and multidrug-resistant virus.²,³ It is given intravenously as a 2,000-mg loading dose followed by 800 mg every two weeks.³

What did the phase 1 study show?

The randomized, placebo-controlled phase 1 study (NCT04027387) enrolled 25 people living with HIV who received single intravenous doses of 400 mg, 800 mg, or 1,600 mg of TMB-365.¹ Participants in the lower-dose cohorts were viremic and not on antiretroviral therapy, while those in the 1,600-mg cohort were on stable combination therapy with suppressed virus.¹

Mean maximum reductions in HIV-1 RNA were 1.55 log10 copies/mL at 400 mg and 1.57 log10 copies/mL at 800 mg, with antiviral effects lasting up to two and four weeks, respectively.¹ In a subset of participants, mean CD4 receptor occupancy remained at or above 80% for five to six weeks at the 800-mg and 1,600-mg doses.¹ No resistance or cross-resistance to TMB-365 or approved entry inhibitors was observed.¹

No serious treatment-emergent adverse events, Grade 3 or higher events, or discontinuations due to adverse events occurred.¹ All 23 treatment-emergent adverse events were mild or moderate, and six events in three participants were considered related to TMB-365.¹ No anti-drug antibodies were detected.¹

“The phase 1 findings demonstrate TMB-365’s antiviral activity in people living with HIV,” Martin Markowitz, MD, medical director of TaiMed Biologics and presenting author of both studies, said in a press release.¹

How could TMB-365 fit into an antibody-only regimen?

TaiMed’s most advanced application of TMB-365 is a pairing with TMB-380, a broadly neutralizing antibody targeting the CD4-binding site on the HIV envelope protein gp120.¹ In laboratory testing, TMB-365 retained activity against viral variants with reduced susceptibility to TMB-380, which the company said supports combining a host-directed antibody with a virus-directed one.¹

In an earlier 20-participant phase 2a study, the TMB-365/TMB-380 regimen was dosed every eight weeks for 24 weeks, and no protocol-defined virologic failures occurred among participants who completed treatment.¹

“TMB-365’s activity against variants with reduced susceptibility to TMB-380 is encouraging,” Markowitz said. “Further clinical studies will determine whether that complementarity translates into durable viral suppression and favorable resistance outcomes.”¹

Extended dosing intervals have become a focus across antibody development. Earlier this week, BioPharm International® reported phase 1 data for a half-life-extended anti-TL1A antibody that may support maintenance dosing every three to six months in inflammatory bowel disease.

Reducing the burden of biologic administration has been a recurring theme in BioPharm International’s interviews. Discussing efforts to shorten administration of intravenous biologics, Charles Theuer, MD, PhD, chief medical officer at Halozyme, said, “You decrease the administration time, literally from hours to minutes and sometimes as little as seconds.”

What happens next?

A phase 2b study comparing the TMB-365/TMB-380 regimen with continued oral antiretroviral therapy is ongoing, with interim results expected by the end of 2026.¹ TaiMed said it also plans to explore combinations of TMB-365 with other antibodies and long-acting small-molecule antiretrovirals.¹

Markowitz will present the phase 1 data in an oral presentation on October 23 and the TMB-365/TMB-380 laboratory data in a poster on October 22.¹

References

1. TaiMed Biologics. TaiMed Biologics Reports IDWeek 2026 Data Highlighting TMB-365 and Its Potential Across Long-Acting HIV Combinations. Press release. GlobeNewswire. Published October 21, 2026. Accessed October 21, 2026.
2. Highleyman L. Ibalizumab, active against highly resistant HIV, now approved in US. aidsmap. Published March 8, 2018. Accessed October 21, 2026.
3. Healio. FDA approves Trogarzo for MDR HIV. Published March 6, 2018. Accessed October 21, 2026.