When it comes to the treatment of cancer, there are a variety of modalities oncologists have in their arsenal by which to treat patients. This depends upon the stage (or how progressed the disease is) of the cancer and the specific type. Patients without disease spread may be eligible to surgical removal of the tumor, however those with advanced disease are really only candidates for radiation and/or drug therapy depending on the cancer type and location. When it comes to drug therapy, there are many different types of drug classes that may be employed. These include traditional chemotherapy, immuno-oncology agents, small molecule inhibitors, antibodies, and the topic of this week, antibody drug conjugates (ADC).
An ADC is a blend of traditional chemotherapy and antibodies. Think of these therapies as heat seeking missiles to tumors. The antibody specifically targets a protein on the surface of the tumor, which helps avoid the ADC targeting normal, non-cancerous cells. Attached to this antibody is the chemotherapy. This is the “business end” of the ADC. Once the antibody targets the tumor and is localized to it, the ADC will release the chemotherapy directly within, or in close proximity, to the cancer cell where it works to kill the cancer. The goal is to reduce the exposure of normal cells to the chemotherapy as the chemotherapy is delivered in a targeted manner via the antibody. Thus, companies developing ADC should be able to avoid systemic side effects of the chemotherapy that is linked to the ADC or alternatively, they may be able to provide higher intensity of chemotherapy via the ADC allowing for a similar side effect profile but with increased efficacy.
The manufacturing of ADCs can be quite tedious, as you have three specific “parts” that need to be carefully combined in a consistent manner. There is the antibody, the chemotherapy, and the linker (what connects the chemotherapy to the antibody). The linker is particularly tedious, as if it is unstable, the chemotherapy will be released while the ADC is circulating in the body before reaching its cancer target. On the flip side, if the linker is too strong, then once it reaches the target cancer, the chemotherapy is not released and won’t kill the cancer. That being said, not all companies venture into the realm of ADCs.
There have been several notable companies in the realm of ADCs. First that comes to mind would be Seagen (ticker: SGEN, formally name Seattle Genetics). Seagen’s bread and butter has been the drug Adcetris (brentuximab vedotin) which has generated more than $1 billion in worldwide revenue annually. They also have recently received approval for a second ADC, Padcev (enfortumab vedotin), which has had a stellar launch despite COVID headwinds. Finally, they have a third ADC under review at the FDA, tisotumab vedotin, with a PDUFA date of October 10th, 2021. There are additional ADCs in development in their pipeline. Another company that has reaped the benefit of the ADC space was Immunomedics (former ticker: IMMU). Immunomedics did not initially receive approval from FDA due to manufacturing issues, but eventually did receive approval for its drug Trodelvy (sacituzumab govitecan). Then, Immunomedics cashed in and was purchased by Gilead for $21 billion. There is also the multibillion dollar collaboration between AstraZeneca and Daiichi Sankyo for the ADC trastuzumab deruxtecan. While the aforementioned companies have had their days in the spotlight with massive moves, there are other small and mid cap companies that are in the ADC space. These include Sesen Bio (ticker SESN) with a drug under review at the FDA, Immunogen (ticker: IMGN) with Phase 3 data due in 4Q21, and ADC Therapeutics which recently received approval for their drug Zynlonta (loncastuximab tesirine). This list of companies in not an exhaustive list of companies, but serves as a starting point for those interested in investing in this potentially lucrative sector.
Disclaimer: I long IMGN.