Last Updated 3/10/2023
Caribou is a gene editing and cell therapy company. They use the CAS12 enzyme with their proprietary chRDNA guide technology. They chose to deploy their technology in developing cell therapies. They are working on T cells ex-vivo and induced Pluripotent Stem Cells for NK cell therapies. I think they are using the CAR-T therapies to test out key edits like PD-1 knockout, MHC I knockout and HLA-E insertion. These key edits can drive advancements in cell therapies. Eventually, they will combine all the successful edits into all their therapies. That will probably require them to move more into iPSC cells as the efficiency would drop significantly by doing that many edits to each cell. Their data showed just 2 targeted insertions dropped the efficiency to about 63% of cells getting all the edits. That is very low if they want to do cell engineering down the road.
I have been following Rachel Haurwitz since Caribou has gone public. I think she has done a good job with managing the company so far. They have some good data in allogeneic CAR-T which shows they are doing good on the science front. I am not sure I am on board with all her decisions though. There is so much more they could be doing with gene editing. They could have an entire pipeline of gene editing programs. Yet they focus on cell therapies which are only a tiny fraction of the size of what gene editing could make.
CB-010 is their CD19 CAR-T therapy where they use allogeneic T cells from donors. They edit these cells to knock out the PD-1 receptor. This protects these cells from the tumor microenvironment by preventing T cell exhaustion. The early data was very impressive for an allogeneic program with 100% complete response rates. The only issue was the durability still fell off at 6 months like other allogeneic programs. The effects of PD-1 knockout improved efficacy, but not durability which is the key issue in allogeneic programs. We should see an update on this program later this year.
CB-011 is their BCMA CAR-T therapy where they knockout the MHC I and replace it with HLA-E. This is designed to prevent cells from being rejected by the host immune system. We know that HLA-E helps prevent NK cell rejection, but not completely. We will have to see how much benefit this edit really gives to durability. They are calling their version of immune evasion Camouflage. They are enrolling the first dose now in the phase 1 trial. We might see some data later in the year.
CB-012 is their CLL1 CAR-T therapy where they knockout the MHC I and replace it with HLA-E, and they knock out PD-1. This is the program I expected as it includes both the edits of the first 2 programs. It will probably set the stage for all their future cell therapies with these key edits. These edits are designed to prevent cells from being rejected by the host immune system and avoid T cell exhaustion. We know that HLA-E helps prevent NK cell rejection. We will have to see how much benefit these edits have combined. This will be targeting AML. It is currently in IND enabling studies.
CB-020 is their preclinical induced Pluripotent Stem Cell platform for NK cells. It is targeting ROR1 which is part of the Wnt signaling pathway. We haven't seen much from this platform so far. I think they are using the T cells to test the edits so they know which ones work best before using them in the iPSC programs.
Cash $317 million
CB-010 is a CD19 program for lymphomas. That is about 75,000 patients in the US. So far this is the best in class allogeneic program. I think it could earn about $500 million in sales unless the data significantly improves. They have some early phase 1 data so I would give it .5 multiple. That is $250 million in value.
CB-011 is a BCMA program for Multiple Myeloma. That is about 30,000 patients in the US. There is no data to inform us to what level of market share it can have. I would guess at least $500 million if the data is good. This gets a .1 multiple for no data yet. That is worth $50 million.
CB-012 is a CLL1 program for AML. That is about 20,000 patients in the US. There is no data to inform us to what level of market share it can have. I would guess at least $250 million if the data is good. This gets a .1 multiple for no data yet. That is worth $25 million.
All in, that is a $642 million market cap. Based on the 61.3 million shares outstanding, that comes to $10.47.
Abbvie Collaboration for up to 4 CAR-T programs. They are entitled to $150 million in development milestones and $200 million of commercial milestones on each of these programs. They will get royalties in the high single digit to low double digit range.
CB-010 Phase 1 Update in 2H of 2023
CB-011 Phase 1 Recruiting Dose 1
CB-012 IND planned for 2H of 2023
Company Website Links
* These are my Opinions and Estimates. They should not be considered financial advice.