Source: GlobalData
South Korea and China stand at forefront of degrader antibody-conjugate development in oncology and other indications, says GlobalData
Posted in Pharma
The emergence of degrader-antibody conjugates (DACs) has attracted much attention, with a potential to transform the precision medicine landscape. DACs aim to address the limitations of traditional antibody-drug conjugates (ADCs) that combine the specificity of antibodies with the potency of protein degraders. DACs represent an emerging class of targeted therapy, with South Korea and China being at the forefront of DAC development in oncology and other indications. The two countries are expected to play an important role in the global DAC market in the coming years, says GlobalData, a leading data and analytics company.
ADCs have three components: a monoclonal antibody (mAbs) that targets a specific antigen, a cytotoxic payload, and a chemical linker. DACs, on the other hand, replace the cytotoxic payload of ADC and merge a proteolysis-targeting chimera (PROTAC) payload with a mAbs via a chemical linker, aiming for targeted protein degradation and potentially improved efficacy and safety.
Currently, DAC development is still in its early stages globally. According to GlobalData’s Pharma Intelligence Center, there are twenty-eight assets in development globally (Phase I: 2; Pre-clinical: 6, and Discovery: 20). South Korean and Chinese companies currently have nineteen assets (South Korea: 10 assets; China: 9 assets) in their pipeline, with one asset in Phase I development for HER2-expressing advanced solid tumors (ORM-5029 from Orum Therapeutics, South Korea).
Nadim Anwer, Pharma Analyst at GlobalData, comments: “Despite notable advances in ADC development, currently available ADCs have limitations related to payload-related toxicity and resistance. DACs have the potential to overcome these challenges by allowing degraders to be delivered directly and selectively to targeted cancer cells.”
South Korea is making significant progress in the DAC sector, riding the partnership wave with many companies. In November 2023, Bristol Myers Squibb acquired potential “first-in-class” DAC ORM-6151 (currently in Phase I) from Orum Therapeutics for approximately $180 million. When the company acquired this drug, it received the FDA’s clearance for a Phase I trial. In July 2024, Vertex Pharmaceuticals and Orum entered into a global collaboration agreement to develop novel DACs.
Several Chinese companies, such as Kangpu Biopharmaceuticals Ltd, Shanghai Helioson Pharmaceutical Co Ltd, and Primelink Biotherapeutics (Suzhou) Co Ltd are prominent players in the development of DACs.
Moreover, in the US, many big players have already jumped into the race to develop DACs. In December 2023, C4 Therapeutics entered into a collaboration agreement with Merck for DACs, where C4 will get $10 million upfront, milestones that could total $600 million and about $2.5 billion across the entire collaboration. In September 2023, Seagen (now part of Pfizer) and Nurix Therapeutics entered a strategic collaboration agreement worth more than $3.4bn for DAC development.
Anwer concludes: “Though most DAC assets are in the early stages of development, they offer a novel and promising solution to overcome the limitations of ADCs. With two Phase I assets in development, coupled with strategic commercial partnerships with big players, provide compelling evidence that DACs could offer a promising therapeutic approach that extends beyond cancer treatment.
“Moreover, with these innovative assets, South Korean and Chinese companies can attract and expand their strategic collaborations with foreign players. It is too early to comment on the clinical success of this class; however, it is gaining attention as a new research area.”