San Diego – New data showcased by Beigene Ltd. at the American Society of Hematology meeting (ASH) provided ample evidence of the company's progress in improving on drugs in two classes of medicine already known for their high-profile leaders. Its anti-PD-1 antibody, tislelizumab, and Bruton's tyrosine kinase (BTK) inhibitor, zanubrutinib, both yielded new data.

Clinical results from a pivotal phase II trial of the company's checkpoint inhibitor, tislelizumab, in Chinese patients with relapsed/refractory (R/R) classical Hodgkin lymphoma found an overall response rate (ORR) of 86 percent, including a complete response (CR) rate of 61 percent, helping to bolster the case for ongoing phase III or potentially registrational trials in a broad array of both solid and hematologic cancers.

But how is the immunotherapy different from the likes of Keytruda (pembrolizumab, Merck & Co. Inc.) or Opdivo (nivolumab, Bristol-Myers Squibb Co.)? Jane Huang, Beigene's chief medical officer for hematology, told BioWorld that company scientists have engineered out the molecule's FC-gamma receptor's interaction with macrophages. That's important, she said, because macrophages sabotage T cells from doing their job.

In preclinical work, Beigene researchers have found that when using nivolumab or pembrolizumab, they see fewer CD8-positive T cells, which are the cells that kill the tumors. With tislelizumab, those T cells are not depleted, she said.

"If you look at Hodgkin's in particular, it may be unique because it's a heavily macrophage-rich tumor, and that's why we may be seeing very interesting results in our clinical data," she said.

The company, which has offices in Cambridge, Mass. and Beijing, is also busy developing a BTK inhibitor called zanubrutinib, for which it presented data on two trials in patients with mantle cell lymphoma (MCL). Results from an ongoing pivotal phase II trial of the candidate in Chinese patients with R/R mantle cell lymphoma (MCL) were featured in an oral presentation at ASH, while updated results from an ongoing global phase I trial in patients with multiple subtypes of B-cell malignancies were shared in a poster presentation.

In the phase II study, the 24-week PFS was estimated at 82 percent. The median PFS had not yet been reached. In the phase I trial, the median PFS for R/R patients was 18 months.

Zanubrutinib is part of the same class as the better-known Imbruvica (ibrutinib, Abbvie Inc./Johnson & Johnson) and Calquence (acalabrutinib, Astrazeneca plc), both of which have FDA approvals for the treatment of second-line MCL. One of the key differences between zanubrutinib and the others "really hinges around our ability to come to very high plasma concentrations for a sustained duration of time," Huang said, a feature she chalked up to greater selectivity for BTK in the Beigene candidate. As with other drugs, greater selectivity can potentially lead to improved safety.

Another point of differentiation for the candidate is greater avoidance of drug-drug interactions, such as with proton pump inhibitors, cumadin and antibiotics, which can lead to issues when taken at the same time as certain BTK inhibitors.

Beigene plans to submit an initial new drug application to the FDA for zanubrutinib in 2019 or early 2020.