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PSW Members….it has been a while since my last post, but since many have all been on the board following the chat, it is time for a scientific lesson in a few of the companies we are long. In addition, another revolution is coming in the medical field, and it will be touched upon as well.
CAR-T – stands for Chimeric antigen receptors (CARs) and the T is for T-cell.
From the picture above, T-cells are one cell type of our immune system that fight off infection as well as they are one player at keeping rogue cells from becoming cancerous. Unfortunately, cancer somehow evades the immune system and so it begins.
CAR-T came along in the late1980s via a brilliant scientist, Zelig Eshhar, an Israeli immunologist at the Weizmann Institue of Science. The basic steps are noted below in picture. The insertion of different 'components' and the way the replication of the protein happens (Step 2; Step 2 subitem 4) yields the clinical variations that are competing in this area by the companies.
KITE, JUNO and Novartis all have CD19 directed CAR-T technologies. CD19 was attractive as a CAR-based target therapy because most B-cell leukemias and lymphomas express it, but normal tissue other than the B cell lineage do not. The companies therefore have focused on CD19 first, and there are subtle difference in the way the T-cells are made.
Any modification of the immune system comes with risk, and CAR-T was no exception. Even thought the CAR-T was hailed as a wonder treatment due to is successes in blood born cancer, it also caused some complications. Last year, JUNO hit the wall with their lead, as it caused severe cerebral edema – cytokine storm?? This caused all the CAR-Ts to be evaluated, but in the end, only JUNO's lead was halted. Companies are continually making progress on the CAR-T front, and BLCM seems to be on the cusp of one way to get around a side effect.
BLCM also has a CD19 directed CAR-T program, with a twist that the physician can give a drug to make the transfected T cells 'turn off' and undergo apoptosis if they themselves go rogue. Other mechanisms are underway as well.
The technology development moving quickly for targeting solid tumors and many forms of pancreatic cancers. There are many others in the space, but these companies noted above are the leaders in the field.
CRISPR
Clustered regularly interspaced short palindromic repeats (CRISPR) is a mouthfull, so CRISPR was born! CRISPR is a defense mechanism used by bacteria, where the 'infecting organisms' are hit with DNA has short repeating sequences to inactivate their genome. Scientists also noted that eurkaryotic systems used a similar mechanism in their adaptive immunity called RNA interference (RNAi), where the cells run a decoy to stop a gene or infection from occurring.
Now companies are running with this techology to turn off or on genes in cells types to fight cancer and many other diseases. It is early on in the cycle, but something will come of it.
This write up will continue to be a point where updates to the technology will be captured. We will continue to monitor the space, as well as many other biotech, small pharma and big pharma companies in the daily chat.
Currently, we are long JUNO, KITE and BLCM.
Trade safe!
– Pharm
