The study, "A DOSE ESCALATION STUDY OF SAFETY & PK OF TMB-365 & TMB-380 IN SUPPRESSED HIV-INFECTED INDIVIDUALS", was presented at The Conference on Retroviruses and Opportunistic Infections (CROI) on March 6, 2024 afternoon. 

TMB-365 and TMB-380, two second-generation broadly neutralizing antibodies, were evaluated in a phase 1b/2a trial for their safety and pharmacokinetic (PK) profiles as a combination therapy in suppressed HIV-infected individuals. The study aimed to assess dose requirement as a complete long-acting regimen for HIV maintenance therapy. The trial included three dose groups, each receiving a single IV infusion of either 2400 mg, 3200 mg, or 4800 mg of each antibody. A total of 30 participants completed the study. The results indicated that the combination therapy up to 4800 mg of each antibody was safe, with prolonged PK duration observed for both TMB-365 and TMB-380. Additionally, approximately 80% of 4800 mg participants met pre-defined trough targets for both antibodies at week 8. No serious adverse events or Grade 3 or 4 adverse events were observed, although there were a total of 32 cases of treatment-emergent adverse events, mostly mild to moderate in severity. The study's results were selected by the conference committee as a Poster-Walk highlight at the CROI conference, receiving positive feedback. A single infusion of TMB-365 and TMB-380 in combination up to 4800 mg each is safe. Prolonged PK duration was observed for both TMB-365 and TMB-380 and results suggest that an every 8-week infusion is feasible and will be tested in a Phase 2a clinical study to obtain efficacy, safety, and other pharmacokinetic information of the dual antibody combination, serving as a reference for evaluating and designing future clinical trials.

The pre-set target drug concentrations in the aforementioned pharmacokinetic trials are established based on clinical data similar to TMB-355 (Trogarzo) for TMB-365, and based on professional evaluation from relevant medical journal literature for TMB-380. Currently, both are set with relatively conservative criteria (i.e., conservative high-level dashed lines in the graph). As more clinical data supports these criteria, there is a possibility of downward adjustment of these dashed lines, accompanied by appropriate dosage adjustments, making the possibility of administering injections every three months quite high. However, this progression will require step-by-step gradual adjustments. Initially, we will develop combinations administered every two months, followed by the development of even longer-acting combinations administered every three months.

First-line maintenance therapy for HIV currently predominantly involves daily oral medication. To meet diverse medication behavior needs, pharmaceutical companies anticipate developing various long-acting drug combinations. These include orally administered drugs taken weekly for convenience, monthly subcutaneous injections administered at home, drug combinations with patient follow-up frequencies at 2-3 month intervals, and potentially achieving 4-6 month ultra-long-acting combinations. Since HIV cannot currently be cured and can only be controlled, HIV patients will select appropriate medication combinations based on their lifestyle, proactive or conservative medication preferences, and physical conditions (such as medication contraindications).

Among all the long-acting HIV medications in development, TMB-365/TMB-380 is the only combination of two different mechanisms of action, requiring only one injection. Compared to combinations from other major pharmaceutical companies that require separate injections of small molecule combinations or small molecule/antibody combinations, TMB-365/TMB-380 possesses distinct market advantages and differentiation.  Our goal at TaiMed is to offer more convenient, safer, fewer side effects, and more versatile long-acting products that meet the diverse needs of patients at every follow-up visit.