Ascletis Begins Study of PD-L1 Antibody Candidate Against HIV

China-based Ascletis has completed the dosing of the first patient in its trial assessing ASC22, a PD-L1 antibody, in combination with chidamide, a histone deacetylase inhibitor, for HIV infection. The dosing was initiated by the Shanghai Public Health Clinical Center. 

Ascletis believes that ASC22 will serve as a “functional cure” for HIV infection. The company last week also announced the first-patient dosing of ASC22 in combination with antiretroviral therapy (ART) for HIV. 

Besides HIV, Ascletis is developing ASC22 for chronic hepatitis B.

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PD-L1 Antibody Against HIV and HBV

A functional cure for HIV/AIDS remains a challenge in China and globally. Even with improvements in ART treatment, the existing therapies often fail to fully eradicate the virus.

ASC22 is a single domain antibody against PD-L1, a popular target in oncology. However, cancer cells are not the only ones who use the PD-1/PD-L1 pathway to evade the immune system. HBV and HIV-infected cells also use the pathway to avoid destruction by immune cells. 

By blocking PD-1/PD-L1, ASC22 restores the ability of immune cells to recognize and eliminate HIV- or HBV-infected cells. With the potential to reverse HIV latency, the antibody could be combined with other drugs to reduce the HIV reservoir of latently infected cells. 

Unlike other PD-L1 antibodies which are administered intravenously, ASC22 is given by subcutaneous injection, giving it an edge. The drug also has a favorable safety profile, and has good stability at room temperature. It was reported to be well-tolerated in chronic hepatitis B patients. 

The other star of Ascletis’ trial is chidamide, a histone deacetylase oral inhibitor that mainly targets subtypes 1, 2, 3 of Class I and subtype 10 of Class IIb histone deacetylase, with a mechanism against epigenetic abnormality. It is the first globally approved drug of its class. 

“The major obstacle that impedes HIV eradication is the persistence of latent reservoir, while current treatments are still ineffective in eliminating HIV reservoir,” stated Dr. Lu Xianping, Founder, Chairman and General Manager of Chipscreen Biosciences.

“Data showed Chidamide safely and vigorously disrupts HIV latency, and therefore it is expected to play a key role in treatment. I expect that the results of Chidamide combined with ASC22 will bring more positive benefits to patients with HIV/AIDS,” Lu said.

Author

Joy Lin

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