Like Merck, Bristol goes to China

Bristol Myers Squibb had stood out among oncology-focused big pharma groups in not having a major presence in antibody-drug conjugates, but that changed today. The company’s $800m licensing of SystImmune’s izalontamab brengitecan, a bispecific ADC that hits EGFR and HER3, ranks as one of the richest ever for a Chinese biotech.

The move is somewhat reminiscent of Merck & Co, which also went to China for ADCs, giving Kelun $222m across two transactions for assets including the TROP2-directed sacituzumab tirumotecan. Merck then struck a monster $5.5bn tie-up with Daiichi Sankyo, and through this it gained patritumab deruxtecan, which shares HER3 targeting as a common feature with SystImmune’s iza-can.

Still, iza-can, also known under the lab code BL-B01D1, has a curious design. At this year’s ASCO conference it was described as a MAb with high affinity for EGFR and low affinity for HER3, comprising a cleavable linker bound to a novel (Ed-04) topoisomerase I payload and featuring a drug-to-antibody ratio of eight.

Pan-killing

The company argues that EGFR and HER3 are highly expressed in various epithelial tumours, and targeting both receptors “could provide a broad-spectrum, pan-tumour killing therapy”. It’s likely that the data presented at ASCO, from a phase 1 first-in-human solid tumour study, spurred today’s deal, under which Bristol is gaining US rights.

Here iza-can boasted a 45% overall response rate, with the highest activity in NSCLC, both EGFR-mutant and wild-type, and nasopharyngeal carcinoma. However, median follow-up was just four months, treatment-related dose reductions were implemented in 25% of patients, 29% experienced severe treatment-related adverse events, and there were two treatment-related deaths; on the plus side, there was no interstitial lung disease.

Meanwhile, a recent San Antonio Breast Cancer Symposium abstract showed activity in a small number of breast cancer patients in a separate trial, again with relatively high rates of grade 3 or higher adverse events.

Interestingly, SystImmune’s pipeline also includes BL-M02D1, an ADC against TROP2. This target is gaining interest because of Daiichi’s AstraZeneca-partnered datopotamab deruxtecan, as well as the Merck/Kelun asset and Gilead’s marketed Trodelvy, but the Bristol deal is for now limited to iza-can.

Izalontamab brengitecan first-in-human data

Source: ASCO & SABCS.