Pinotbio releases preclinical results of new drug and linker at AACR 2024
Pinotbio is increasing its competitiveness on the global stage by emphasizing effectiveness and safety by combining the “PBX-7 Series” and “sequential cleavage linker.”
Pinotbio, an ADC platform company, said Monday that it unveiled preclinical results of its ADC platform at the American Association for Cancer Research (AACR) 2024 in San Diego, Calif.
The AACR, one of the world's three largest cancer societies, discusses research results and the latest trends in anticancer drug development. Following last year, Pinotbio participated in AACR 2024 and unveiled additional data and new linkers of its self-developed ADC payload (drug) “PBX-7 Series” for the first time.
According to the presentation, the PBX-7 Series demonstrated superior anticancer efficacy and excellent safety profile compared to Enhertu in various preclinical models. In an animal model implanted with a breast cancer cell line (JIMT-1) that had developed resistance to Roche's HER2-targeting ADC Kadcyla compared to Enhertu.
In addition, the three new drugs' in vitro experiments showed a “bystander effect” that was more than equivalent to that of Enhertu. The bystander effect is a mechanism by which the drug spreads around the target and kills neighboring cancer cells, one of Enhertu's key competitive advantages. Safety testing also showed excellent results in primate model toxicity, with no adverse effects observed at doses up to 30 mg/kg.
The sequential cleavage linker, which Pinotbio independently developed, was also unveiled for the first time. This linker releases the drug only when two types of enzymes work in sequence and is characterized by dramatically increased hydrophilicity.
In the case of conventional single-enzyme linkers, some drugs are separated outside the cell, causing systemic toxicity. Sequential cleavage linkers, on the other hand, are designed to release drugs only when two enzymes, which cannot work simultaneously due to their structure, work in sequence, minimizing the uptake of anticancer drugs into normal cells while maintaining their effectiveness. That reduces the risk of side effects, such as interstitial lung disease (ILD) and neutropenia, common with conventional ADCs.
"Following the development of the ‘PBX-7 Series’ payload, we are pleased to further enhance and expand our ADC platform technology by securing a new linker technology with excellent performance," Pinotbio CEO Jung Doo-young said. "We will do our best to achieve 'efficacy' and 'stability' simultaneously."