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TMB-355 (Ibalizumab)


TMB-355(Ibalizumab) is a humanized monoclonal antibody (mAb) and a member of an emerging class of HIV therapies known as viral-entry inhibitors. This drug candidate is distinct from other entry inhibitors in that it binds to the CD4 molecule, the primary receptor for HIV infection, thereby interfering with the penetration of the virus into the cell. It is the first entry-blocking humanized mAb to treat HIV/AIDS. TMB-355 caught the attention of the scientific community in February 2003, when results from the phase-1, single-dose, intravenous infusion (i.v.) clinical trial showed a transient but clinically significant reduction in the patients’ viral load. Moreover, it was well tolerated with no evidence of adverse effects on CD4 T-cells of treated subjects unlike the majority of approved drugs for HIV. U.S. FDA granted TMB-355 fast track status in October 2003. The phase-2a clinical trial was successfully completed in 2006, with the results showing a clean safety profile and clear antiviral activity (10-fold reduction in viral load). The Phase-2b clinical trial was also successfully completed in 2011, with the confirmation of a good safety profile and strong antiviral activity in HIV patients with multidrug resistance (MDR). U.S. FDA granted orphan drug designation of TMB-355 for HIV patients with multidrug resistance in 2014. Moreover, TaiMed received breakthrough therapy designation from the U.S. FDA for TMB-355 in 2015, which provides the privilege for a rolling biologics license application (BLA) submission. An on-going pivotal phase-3, single-arm clinical trial with patient number of 30 is blessed by U.S. FDA and will be completed in 2016. The clinical trial results, along with other available CMC, pre-clinical, and clinical data, will be submitted as BLA package in 2016 under rolling review. TaiMed Biologics also developed a subcutaneous injection (s.c.) dosage form and the phase-1 human pharmacokinetics bridging study was completed in 2012. Currently, TMB is also developing an intramuscular injection (i.m.) dosage form and a phase-1/2 study for HIV-negative and naive HIV-positive subjects is on-going.


-        2003: completed a phase-1a clinical trial for i.v. infusion dosage form

-        2003: granted fast track status by U.S. FDA

-        2003: completed a phase-1b clinical trial for i.v. infusion dosage form

-        2006: completed a phase-2a clinical trial for i.v. infusion dosage form

-        2011: completed a phase-2b clinical trial for i.v. infusion dosage form

-        2012: completed a phase-1 clinical trial for s.c. injection dosage form

-        2013: initiated a phase-1/2 clinical trial for s.c. and i.m. injection dosage forms (on-going)

-        2014: granted orphan drug designation for HIV MDR patients by U.S. FDA

-        2015: granted breakthrough therapy designation for i.v. infusion dosage form by U.S. FDA

-        2015: initiated a phase-3 clinical trial for i.v. infusion dosage form (on-going)

-        2016: initiated and intended to complete a rolling BLA submission for i.v. infusion dosage form to U.S. FDA



TMB-355 Intravenous Infusion Dosage Form Development

With an on-going phase-3, single-arm clinical trial, TMB-355 intravenous infusion dosage form is the flagship pipeline of TaiMed and nearly ready for the market. The study design of 2000 mg loading dose followed by 800 mg bi-weekly dose is blessed by U.S. FDA and the patient number of 30 is incredibly small for a phase-3 pivotal trial.


TMB-355 i.v. infusion dosage form has demonstrated not only a clean safety profile but also tremendous efficacy on HIV MDR patients. Compared to placebo, TMB-355 in combination of optimized background regimen (OBR) resulted in statistically significant viral load reduction and clinical meaningful CD4+ cell increasing in the phase-2a clinical trial with treatment-experienced HIV patients. TMB-355 was well tolerated with no infusion-site reactions, no serious adverse events, and no laboratory abnormalities. In addition, good patient adherence to study visits and acceptance of intravenous administration were observed.


In the phase-2b clinical trial with 113 HIV MDR patients, the safety and the efficacy profiles were observed and confirmed. In combination of OBR, both dose groups of TMB-355 resulted in more than 10-fold reduction in viral load in 60% of overall patients with no drug-related serious adverse events. Un-detectable viral load (<50 copies/mL) was observed in 36% of overall patients (ITT-MEF). TMB-355 was well tolerated with the comment serious events of rash and nausea which are manageable.


Phase-2b Clinical Trial Study Outcomes (Virologic Endpoints, ITT-MEF)


800mg q2w

2000mg q4w


Dosage and Regimens

One injection per 2 weeks with 800 mg TMB-355
(800mg /2 weeks)

One injection per 2 weeks with 2000 mg TMB-355 or vehicle alternately
(2000mg /4 weeks)

800mg / 2 weeks or 2000mg / 4 weeks

No. of Subjects (N)




% of Subjects with Viral Load < 400 copies/ml (%400)




% of Subjects with Viral Load < 200 copies/ml (%200)




% of Subjects with Viral Load < 50 copies/ml (%50)




% of Subjects with Viral Load Reduced by 90% Above (%1 log drop)




Mean; Log10 change from baseline




Median; Log10 change from baseline






A 30-patient phase-3 clinical trial is initiated in U.S. and Taiwan in 2015 and will be completed in 2016. The primary endpoint is the proportion of patients achieving more than ~3-fold reduction (0.5 log reduction) in vial load 7 days after loading dose. The current available un-audited data shows very encouraging results.


BLA submission for TMB-355 i.v. dosage has been initiated. With rolling review, the whole submission process, including pre-approval inspection, will be completed in 2016.


TMB-355 Subcutaneous / Intramuscular Injection Dosage Form Development

To pursue more convenient uses of TMB-355, TaiMed has subcutaneous (s.c.) and intramuscular (i.m.) injection dosage forms under development. The dosages will provide the patients more options for drug administration, and have the potential to apply only bi-weekly or monthly. The phase-1 clinical trial of the s.c. dosage was funded by the Bill & Melinda Gates Foundation, and was completed in 2012 in U.S. The results indicated the potential use of TMB-355 for HIV prevention. A phase-1/2 clinical trial of the s.c. and i.m dosages with HIV negative volunteers and HIV patients is initiated in 2013 in Taiwan.  The current available un-audited data shows tremendous antiviral activity in both s.c. and i.m. dosages with no additional safety concern, and the possibility as an alternative route of i.v. dosage for HIV MDR via label extension. A phase-2/3 clinical trial is planned in 2016 as an option of HIV frontline therapies.