What are pd-1 inhibitors, three main features of pd-1 products

Before understanding pd-1 inhibitors, let's first popularize what PD-1 is.PD-1 is a protein present on the surface of T-cells, which usually prevents immune cells from functioning normally, and thus fails to timely and effectively remove tumors with high microsatellite instability in the human body, which have hundreds or even thousands of mutations, leading to systemic metastasis of the tumors. PD-1, on the other hand, eliminates the inhibition of T-cell activity by tumor cells by blocking the combination of PD-1 on T-cells and PD-L1 on tumor cells, improves the ability of T-cells to kill tumors, and thus utilizes the body's own immune function to kill tumor cells. Simply put, PD-1 is a drug used in clinical practice to treat tumors.

Figure 1?Mechanism of action of pd-1

Pd-1 inhibitors What are they

There are six domestic PD-1 products approved for marketing in China: 1. Tirilizumab of Baizi Divine, with approved indications including relapsed/refractory classic Hodgkin's lymphoma and uroepithelial carcinoma. 2. Pembrolizumab of Merck Sharp & Dohme. 3. Teraplizumab of Junshi Bio. Pembrolizumab of Merck Sharp & Dohme; 4, Sindelizumab of Cinda Biologics; 5, Karelizumab of Hengrui Pharmaceuticals; 6, Navulizumab of Bristol-Myers Squibb;

Three major features of Bazenan pd-1 inhibitor:

1. Durable blockade of the Fab segment

Among the Bazenan's pd-1 inhibitor, the Bazenan is distinguished from other drugs by its unique antigen-binding epitopes, the The affinity of Bazedan is significantly higher than that of similar antibodies. As shown in the figure below, the affinity for PD-1 is significantly higher and the dissociation rate is slower than that of other drugs, resulting in a more sustained blockade.

Figure 2 Comparison of affinity and dissociation rate of different PD-1 drugs

Unique modification of Fc segment

Bazenan is a PD-1 inhibitor that is more modified in the Fc segment of the constant region. The unique structural modification of the Fc segment of its antibody reduces the binding to FcγR on the surface of macrophages, which will no longer attack T cells, reducing T cell consumption and improving anti-tumor efficacy.

Long half-life

Previous studies have shown that the longer the half-life of an antibody, the stronger its anti-tumor activity. The chart below shows a comparison of the half-life of several pd-1 products.

Figure 3 Half-life of antibodies (days)

Since the domestic launch of Baizian in 2019, it has been approved by the NMPA for the treatment of locally advanced or metastatic uroepithelial carcinoma in relapsed or refractory classical Hodgkin's lymphoma that has undergone at least second-line systemic chemotherapy and locally advanced or metastatic uroepithelial carcinoma that has failed platinum-containing chemotherapy including progression within 12 months of neoadjuvant or adjuvant chemotherapy with high PD-L1 expression.

In addition, Bazedion has 16 potential registrational clinical trials underway covering multiple tumor types including lung, liver, esophageal, gastric, nasopharyngeal, and solid tumors with high microsatellite instability or mismatch repair defects. Bazedion is less expensive than many other drugs in its class currently on the market, and is also reimbursed by a number of health insurances, further increasing its accessibility.