Antibodies have been proven as excellent tools for specifically targeting cancer cells, however, the damage they inflict upon cancer cells is minimal, especially when compared with chemotherapy drugs. According to many observers, including ourselves, the field of cancer antibodies is poised for some exciting changes, as it evolves towards more advanced antibody-based therapies. In our opinion, the inevitable next step is arming antibodies with effector molecules such as protein toxins, radioisotopes and chemotherapy drugs. This may result in superior anti-cancer treatments that possess the specificity of antibodies on the one hand and the potency of chemotherapy on the other. Such treatments, generally referred to as immunoconjugates, are desperately needed, especially for the treatment of solid tumors.
Since we believe the field of immunoconjugates is finally reaching maturity, companies that focus on developing monoclonal antibodies such as Medarex (MEDX), Genentech (DNA) and Imclone (IMCL) will most likely enjoy the trend, thanks to their experience and broad portfolio of antibodies for cancer. However, companies that specialize in developing immunoconjugates, instead of just “naked” antibodies, represent a more lucrative opportunity. And when it comes to investing in such pure-plays, it doesn’t get any better than Immunogen (IMGN). Because the market for immunoconjugates is still in its early stages, Immunogen bears a high risk, even when compared to other small drug development companies. Nevertheless, Immunogen, which has been developing immunoconjugates for over 25 years, is the best positioned company in the field, as it has gained unparalleled knowledge, experience and intellectual property. Therefore, we expect Immunogen to play a very important role in the antibody market, although the exact timing and dynamics are still vague.
Immunogen focuses on a sub-type of immunoconjugates called “Antibody-Drug conjugate” [ADC], where the antibody is linked to chemotherapy drugs. ADCs are expected to comprise a substantial portion of immunoconjugates that enter clinical stages in the coming years due to their excellent suitability for treating solid malignancies. Upon being injected to patients, the antibody portion of the ADC homes on cancer cells and binds them. Following the binding, the ADC is internalized into the cancer cells followed by release of the drug inside the cell. The chemo drug has no effect when circulating in the blood stream, but only once it is inside the cancer cells.
Radio-immunoconjugates such as Bexxar® and Zevalin®, where the antibodies are conjugated to radioactive molecules, have been proven to be very effective in the treatment of blood cancers but their use for solid malignancies is problematic. The thing with radioisotopes is that they cannot be switched on and off. Since they are constantly emitting deadly radiation, they affect everything they encounter on the way to the tumor. This leads to limitations in the amount of radioactive molecules that can be injected to patients, which is a crucial issue when dealing with solid tumors. ADCs, on the other hand (if properly built), affect only tumor cells and their nearby surroundings, which enables the injection of relatively large amounts of the antibody-drug conjugate. It doesn’t mean that radio-immunocojugates cannot be used for the treatment of breast and lung cancers, but only that ADCs are more suitable for this task.
Author is long IMGN