May 19, 2024

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Biopharma companies bet wildly on ADC: About 1000 in development

Biopharma companies bet wildly on ADC: About 1000 in development



 

Biopharma companies bet wildly on ADC: About 1000 in development


In March of this year, Pfizer announced the $43 billion acquisition of Seagen, the leader in Antibody-drug conjugate (ADC).

Other biopharma giants such as AstraZeneca, BioNTech, and Bristol-Myers Squibb have all placed big bets on ADCs recently.

 

Biopharma companies bet wildly on ADC: About 1000 in development

 

 

In February, AstraZeneca acquired the global rights to the ADC from KYM Biosciences for an upfront payment of $63 million.

 

In April, BioNTech signed a $170 million licensing deal with China’s Duality Biologics for exclusive rights to two ADCs, while Bristol-Myers Squibb secured German biotech Tubulis to develop The right to use an ADC technology.

 

This recent spate of deals is just one sign of big biotech and drug companies betting big on ADC.

 

According to Hanson Wade analysis, 2022 is a record year for ADCs entering the clinical stage. In 2022, 57 ADCs entered Phase I clinical trials, an increase of more than 20 from the previous year.

 

ADC technology is not new. The first marketed ADC, Mylotarg, was approved by the US Food and Drug Administration (FDA) in 2000. Since then, more than 14 ADCs have been approved worldwide, and nearly 1,000 drugs are clinically or preclinically active.

 

Between 2019 and 2022, eight ADCs have been approved by the FDA.

Third-generation ADCs, which show less off-target toxicity and avoid initiating the body’s immune response, are leading the new wave.

 

This is thanks in part to advances in protein engineering that have created more stably attached ADCs that can reach tumors before releasing their payloads. Newer ADCs are also site-specific, meaning their cytotoxic payload molecules attach to a precise location on the antibody molecule.

 

A prime example of third-generation ADC technology is AstraZeneca and Daiichi Sankyo’s Enhertu (fam-trastuzumab deruxtecan-nxki), which was approved under the FDA’s accelerated pathway in December 2019 for the treatment of HER2-positive metastatic breast cancer.

Phase III trial data showed that Enhertu reduced the risk of disease progression or death by 72% in patients previously treated with other cancer-targeted drugs.

 

Despite the widespread success of ADCs in clinical trials, there are many risks.

 

The first, and main, drawback is that tumors can develop resistance to them over time. Toxicity is also a concern, especially as cytotoxic loads become increasingly potent.

 

Secondly, in terms of business, the competition in this field is indeed becoming more and more fierce, and we are beginning to see the phenomenon of clustering biological targets. From an investor’s perspective, this is a risk.

 

 


What is Antibody-drug conjugate (ADC)?


An antibody-drug conjugate (ADC) is a type of targeted therapy used in the field of cancer treatment. It combines the specificity of monoclonal antibodies with the potency of cytotoxic (cell-killing) drugs, aiming to deliver the drug directly to cancer cells while minimizing damage to healthy cells.

 

ADCs consist of three main components: an antibody, a cytotoxic drug, and a linker molecule.

The antibody is designed to specifically recognize and bind to certain proteins or antigens that are overexpressed on the surface of cancer cells. This targeting mechanism helps ensure that the drug is delivered primarily to cancer cells.

 

The cytotoxic drug, often a potent chemotherapy agent, is attached to the antibody through the linker molecule.

The linker serves as a bridge between the antibody and the drug, keeping them connected until the ADC reaches the target cancer cell.

Once the ADC binds to the cancer cell, it is internalized, and the linker is cleaved, releasing the cytotoxic drug inside the cell. The drug then exerts its toxic effects, leading to cell death.

 

By selectively targeting cancer cells, ADCs can potentially enhance the efficacy of the drug while reducing the systemic toxicity associated with traditional chemotherapy.

This targeted approach may also improve the therapeutic index, allowing for higher doses of the drug to be administered.

 

Several ADCs have been developed and approved for the treatment of various types of cancer.

Examples include Adcetris (brentuximab vedotin) for Hodgkin lymphoma and certain types of non-Hodgkin lymphoma, Kadcyla (ado-trastuzumab emtansine) for HER2-positive breast cancer, and Enhertu (trastuzumab deruxtecan) for HER2-positive breast and gastric cancers.

 

ADCs continue to be an active area of research and development, with efforts focused on improving their efficacy, safety, and expanding their applications to different types of cancer.

 

 

Biopharma companies bet wildly on ADC: About 1000 in development

(source:internet, reference only)


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