Baili moves its CD33 conjugate into advanced trials

Baili Pharmaceutical is preparing to advance its CD33-targeting antibody-drug conjugate BL-M11D1 into a phase 2/3 trial in China, in what appears to be a rare attempt to revive interest in an ADC target that has not seen a lot of good news.

A new clinicaltrials.gov entry indicates that the study will evaluate BL-M11D1 as a first-line treatment for acute myelogenous leukaemia in combination with either Vidaza and Venclexta, or cytarabine and daunorubicin. Overall response rate is the most important co-primary endpoint.

The company presented early monotherapy data at ASH last year, where it reported responses beginning at 1.65mg/kg in patient with relapsed AML. Across 1.65mg/kg, 2.2mg/kg and 2.75mg/kg dose levels ORRs were 14% (one of seven patients), 43% (6/14) and 50% (2/4). 

However, the company also reported two deaths that were considered potentially related to BL-M11D1, both being due to infection. Until the latest phase 2/3 effort BL-M11D1 has only been studied in two phase 1 trials.

CD33 ADC setbacks

With this study, the company is positioning its ADC to enter a mechanistic approach long defined by setbacks.

Pfizer’s anti-CD33 ADC Mylotarg was the world’s first ADC approved, but in 2010, 10 years after its accelerated approval, the drug was withdrawn after confirmatory studies questioned its safety and efficacy, making it the first drug removed from the market after an accelerated approval. Seven years later, in 2017, the FDA reapproved the drug at a lower dose, and with a revised dosing schedule.

That same year, Seagen discontinued its CD33-targeting ADC vadastuximab talirine, after interim data showed a high rate of deaths, including fatal infections, in its phase 3 treatment arm. And since then the field has thinned to nearly nothing.

According to OncologyPipeline, Hangzhou DAC is the only other company running a clinical trial of a monospecific CD33-targeting ADC, DXC007. Meanwhile, Bristol Myers Squibb is trying a different angle with a CD33/GSPT1-targeting degrader-antibody conjugate, BMS-986497, that the company acquired from Orun; its first study isn’t expected to hit primary completion until 2027.