4:41 PM
Apr 26, 2018
 |  BC Innovations  |  Product R&D

Brake for gas

China newco Elpiscience links 4-1BB boost to PD-L1 block in first of 12 programs

Elpiscience Biopharmaceuticals Co. Ltd. has emerged from stealth mode with an unconventional bispecific that simultaneously removes the brakes and steps on the gas for antitumor immunity, but only inside tumors. The goal is to upstage leading immunotherapies by widening the gap between efficacy and toxicity.

Backed by Lilly Asia Ventures and headed by venture partner and former Roche BD&L executive Darren Ji, the newco is the latest example of the momentum in China for harnessing innovative science to compete both locally and globally. Ji, who co-founded the company as CEO in 2017, unveiled the company’s lead compound and pipeline strategy at the China Healthcare Investment Conference (CHIC) meeting last month in Shanghai.

Elpiscience is stocking its oncology pipeline through a mix of business development and internal R&D using an in-house suite of immunological assays to gauge how compounds affect key parameters like T cell exhaustion, NK cell cytotoxicity and myeloid-derived suppressor cell (MDSC) activity.

The company in-licensed its lead program from Inhibrx LLC -- a bispecific antibody with a structure that makes activation of the T cell costimulatory receptor 4-1BB dependent on PD-L1 blockade.

Elpiscience has Chinese rights to the compound, dubbed ES101, while Inhibrx holds U.S. and other global rights under the name INBRX-105. Both companies are submitting INDs to test the compound in solid tumors in their respective territories this year. Starting in Phase II, according to Ji, they plan to use a unified protocol and consolidate patients.

While most bispecific antibodies use each arm to target a different antigen, ES101 contains two identical arms that each target both antigens. The structure allows each arm to bind PD-L1 on tumors and 4-1BB on T cells simultaneously (see “On the Same Side”).

Figure: On the same side

Elpiscience Biopharmaceuticals Co. Ltd. and Inhibrx LLC partnered to develop ES101 (INBRX-105), a bispecific antibody that simultaneously blocks the checkpoint molecule PD-L1 on tumor cells and activates the costimulatory molecule 4-1BB on T cells.

Most bispecific antibodies use each arm to target a different antigen. ES101 contains two identical arms, each targeting both antigens. Each arm contains humanized, llama-derived single domain antibodies against PD-L1 (PDL1: sdAb) and 4-1BB (41BB: sdAb) linked to an Fc domain that lacks effector function but improves the compound’s PK profile.

When ES101 binds PD-L1 on tumor cells, it also binds 4-1BB on tumor-engaged T cells. By binding 4-1BB via both arms, ES101 induces clustering of 4-1BB molecules on the T...

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