United BioPharma Received IND Approvals from Taiwan FDA and China NMPA for two Phase 2 Studies with UB-421 Monotherapy and in Combination with Chidamide to Evaluate the Application in HIV Functional Cure
United BioPharma (UBP) announced today that two separated Investigational New Drug (IND) approvals have been granted by Taiwan FDA (UBP protocol No. A232) and by China National Medical Products Administration (NMPA; protocol No. A230) for two phase 2 proof-of-concept (POC) trials with UB-421 (an anti-CD4 monoclonal antibody) monotherapy alone or in combination with chidamide, a latency reversal agent (LRA), among virally suppressed patients under stable treatment with antiretroviral therapy (ART) to evaluate the application in HIV-1 functional cure. The objective is to examine the reduction of HIV reservoirs and dynamics of related biomarkers that may shed lights into the mechanism of “shock-and-kill” to achieve the HIV functional cure. The two POC studies with slightly different designs will be conducted in Kaohsiung Veteran General Hospital, Taiwan (A232 trial) and Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangdong China (A230 trial), respectively.
The "Shock and Kill" approach is one of the widelystudied HIV functional cure strategies, that is to activate latent viral reservoirs (Shock) to express HIV antigens on the cell surface so that immune cells can recognize and purge the latently infected T cells (Kill) and subsequently lead to the reduction of the size of reservoirs. Chidamide, a broad-type histone deacetylase (HDAC) inhibitor with low toxicity and relatively good safety profile, may contribute to this approach. The results from previous small trials in Chinese HIV patients show that 10 mg or 30 mg of chidamide twice per week on top of ART for 4 weeks can trigger intermittent transcription of latent HIV DNA (measured in cell-associated [CA-] RNA), and may reduce viral reservoir (measured by HIV total DNA) up to 50% as compared with the baseline levels in part of participants. UB-421 is a strong entry inhibitor of HIV with proven ability to substitute for ART, and it may also enhance CD8 T cell cytotoxicity function and improve immune exhaustions; thus UB-421 can provide dual capacities, as a monotherapy to suppress virus replication and prevent new infection, and as the “killing” agent to reduce HIV reservoir cells during the studies.
The A232 single-arm study in Taiwan will enroll up to 10 HIV-1 viraly suppressed and ART experienced adults to switch his/her treatment regimen to 10 mg/kg weekly UB-421 plus 10 mg chidamide twice weekly for 8 weeks. The A230 two-arm randomized open-labelled study in China will further compare the effect of combo therapy to that of monotherapy with UB-421 alone. In this trial, 20 qualified HIV-1 suppressed adults will be enrolled; 10 subjects will receive the combination treatment while the other 10 receive only UB-421 treatment. In addition to investigate the dynamics of reservoir changes, other clinical endpoints of the two trials will include CD4 and CD8 T cell enumeration, PK and intensive laboratory examination and safety monitoring.
Chidamide is an orally bioavailable subtype-selective histone deacetylase (HDAC) inhibitor, approved in China for indications of recurrent and refractory peripheral T cell lymphoma (in Dec. 2014) and hormone receptor-positive, HER2-negative advanced breast cancer (in Nov. 2019). In clinical experiences of cancer treatment, chidamide (commercial names Tucidinostat, HBI-8000 or Epidaza) demonstrated favorable pharmacology and better tolerability profiles as compared to existing HDAC inhibitors.
Chidamide works against the tumor cell development through epigenetic modulations, which can decrease expressions of classes I and IIb HDACs to partially activate the transcription of cell DNA, including the integrated HIV DNA in the infected host chromosome. By its epigenetic mechanism, chidamide can induce preferential growth arrest and apoptosis of lymphoid-derived tumor cells, and result in the activation of NK-mediated and CD8-mediated antigen-specific cellular anti-tumor immunity. HDAC inhibitors have been previously evaluated for the function of HIV latency reactivation, and chidamide can promote high level expressions of HIV proviral DNA among many HDAC inhibitors being tested.
Chidamide is developed by Chipscreen Bioscience, Shenzhen, Guangdong, China, and it’s collaborator and commercial representative in Taiwan, GNT Biotech and Medicals Corporation (GNTbm], Taipei, Taiwan.
About United BioPharma
United BioPharma (UBP) is a late clinical stage biopharmaceutical company that is dedicated to the research, development and manufacture of novel monoclonal antibodies (mAbs) for infectious diseases, cancer and immune disorders. UBP is headquartered in Taiwan, with subsidiary companies in Shanghai and Yangzhou China, and liaison offices in the U.S. The company has a highly passionate global team, developing first-in-class, best-in-class therapeutic mAbs and delivering high-quality, affordable treatments to bring a better quality of life to patients. For more information, please visit the website at: http://www.unitedbiopharma.com
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Dr. Mei June Liao, Executive Vice President, Product Development
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