TMB-365 was successfully completed the phase I study, and the data results far exceeded the original set standards

2021-10-01

  1. Protocol Title: A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Sequential Single Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of the Intravenous Administration TMB-365 in HIV-1 Infected Participants

  2. Participants and Investigator Sites: A total of 26 participants from approximately 6 sites in North America.

  3. Primary Objectives:

a. Evaluate the safety and tolerability of a single IV infusion of TMB-365 in doses of 400 mg, 800 mg, and 1600 mg in HIV-1 infected participants

b. Evaluate the pharmacokinetic (PK) profile of TMB-365 after a single IV infusion of doses of 400 mg, 800 mg, and 1600 mg in HIV-1 infected participants.

c. Identify a suitable dose range of TMB-365 for further study.

      4. Study Phase: Phase 1

      5. Protocol Number: TMB-365-101

I   Study Design:

This randomized, double-blinded, placebo-controlled, sequential single dose escalation study will evaluate the safety, tolerability and PK parameters of TMB-365 administered via IV infusion to HIV-1 infected participants. The study involves the administration of 400 mg, 800 mg, or 1600 mg of TMB-365 or matching placebo. All participants will be monitored for 10 weeks post-administration.

II   Study Results:

A single dose of TMB-365 at 400 mg, 800 mg, or 1600 mg is well tolerated. The safety and tolerability are as expected. The primary objective of this study is to identify a suitable dosing regimen of TMB-365 for further studies by evaluating the PK profiles of TMB-365 after administration of different doses. The original targeted dosing frequency was monthly dosing (Note: the market drug Trogarzo® is biweekly dosing). But, the results are far better than we expected. It suggested that bimonthly dosing, or even quarterly dosing, is likely achievable with appropriate doses. We have submitted the study results to the FDA and requested a pre-IND meeting for a phase 2a study of a combination of TMB-365 and TMB-380.

III  Future Marketing Plan:

The phase 1 study results demonstrated that TMB-365 is a long-acting drug. The target market is completely different from the first generation drug, Trogarzo®, which is targeting to the patients with multi-drug resistance. In combination with TMB-380 (VRC07-523LS), which is licensed from NIH, as a complete regimen of monoclonal antibodies with bimonthly or quarterly dosing, the target population is the first line HIV treatment (maintenance therapy) with ten billion dollars of marketing opportunities. NIH has completed a phase 1 study of TMB-380 with bimonthly dosing. A combination of TMB-365 and TMB-380 will enable physicians to help more patient to achieve long term virological suppression with better tolerability, allow more patients to be retained in care and reduce the risk of accelerating the development of treatment resistance virus variants. To date, there is only one long-acting regimen for maintenance therapy on market, which is GSK’s Cabenuva monthly injectables, a combination of two small molecular drugs.