Big players in the biopharma industry are placing significant investments in antibody-drug conjugates (ADCs). In March, Pfizer announced its plan to acquire Seagen for $43 billion. In February, AstraZeneca paid over $60 million to obtain the worldwide rights to KYM Biosciences’ ADC. In April, BioNTech signed a $170 million agreement with Duality Biologics to exclusively access two ADCs, while Bristol-Myers Squibb obtained the rights to an ADC technology created by Tubulis. These recent deals signify a trend in the industry’s reliance on ADCs.
Biopharma’s investments in Antibody-Drug Conjugates (ADCs)
- ADCs are a promising cancer therapy that comprises a monoclonal antibody, a potent cytotoxic agent, and a linker that connects the two, designed to destroy cancer cells while leaving healthy tissue unharmed.
- Recent advancements in protein engineering have led to more stable ADCs with improved precision and reduced off-target toxicity issues and immune response activation.
- Despite their success in clinical trials, ADCs have limitations, such as the development of resistance over time and the risk of toxicity with more potent cytotoxic payloads.
- Companies are investing in and developing ADCs to reduce the chances of competitors creating biosimilars, allowing them to maintain high ADC prices for longer than conventional drugs. Researchers will need to continue improving the technology to overcome the challenges of ADC therapy.
The success of drugs such as Gilead’s Trodelvy, designed to treat HER2-negative metastatic breast cancer, which earned $222 million in Q1 2023, a 52% increase from last year, is one of the reasons for the industry’s focus on ADCs.
ADC technology has been around since the FDA approved the first ADC, Mylotarg, in 2000. After the aforementioned developments, more than 14 additional ADCs have obtained global market approval, and approximately 1,000 drugs are in clinical or preclinical testing stages. ADCs comprise a monoclonal antibody designed to attach to antigens on cancer cells, a potent cytotoxic agent like a chemotherapy drug, and a linker that connects the two. The aim is for the ADC to specifically identify and destroy cancer cells while leaving healthy tissue unharmed, akin to a guided missile.
Newer third-generation ADCs have improved upon the off-target toxicity issues and immune response activation that plagued earlier ADCs. These improvements are the result of advancements in protein engineering which have led to more stable ADCs. They are better equipped to reach the tumor cells and release their payload.
While ADCs are a promising cancer therapy, they are not without limitations. One of the main challenges is the development of resistance to ADCs over time, and there is also a risk of toxicity, especially with more potent cytotoxic payloads. To fully optimize ADC therapy, researchers will need to address these issues by improving the stability of linkers, identifying more specific therapeutic targets, and finding ways to overcome resistance.
On the business side, companies are investing in and developing ADCs to reduce the chances of competitors creating biosimilars, allowing them to maintain high ADC prices for longer than conventional drugs. Hsieh noted that the field is becoming crowded, with biological targets being stacked.
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