Thread by @Biotech2k1

@HassanAesthetic Profile for $CRBU

1/ This might be the most recent of CRISPR IPO's, but its one of the oldest companies with this technology. Rachel was part of the Jennifer Doudna team, and they worked together to form $CRBU.

2/ I followed this company for a long time as a private company when I got interested in CRISPR a few years ago. They are the holder of all the Doudna patents for CAS9 and CAS12. They license completely the CAS9 to $NTLA which they did for a share stake in the company.

3/ Over the years they sold off that stake to fund their own development of chRDNA. They reverse licensed CAS9 from $NTLA for use in their lead product CD010 under a patent dispute. They have full ownership of their CAS12 and chRDNA technology.

4/ They use standard CAS12 enzyme for their nuclease. This is smaller than the CAS9 enzyme, and it does staggered breaks which are easier to repair. The real innovation was the new chRDNA guides they developed.

5/ This stands for chimeric RNA/DNA guides. All CRISPR CAS enzymes use fully RNA guides. The chRDNA uses key bases as DNA. The DNA bases bind better to the DNA than the RNA bases.

6/ This allows for them to bind key bases in the DNA and use them to as anchors to align the CAS enzyme for more accurate cutting. It allows for more efficient cutting and less off target cutting.

7/ They are the only CRISPR company to be fully focused on cell therapies ex-vivo. Their first 2 indications are CAR-T in CD19 and BCMA which are the classic starting point to prove the tech works. You can easily compare to other CD19 or BCMA data.

8/ They are actually on the leading edge of CAR-T cell editing. They do the CAR inserting into the TRAC locus which increases the persistence and performance. They are doing PD-1 knockouts, and they do the insertion of the HLA-E into the B2m locus.

9/ These are some of the most powerful edits in CAR-T therapies. They also realize the need between CAR-T in blood cancers and CAR-NK in solid tumors. This is a need most companies haven't figured out yet. They are moving toward iPSC manufacturing for their NK cell programs.

10/ Most of these lead assets for CD19 and BCMA probably won't make much money. There is about 30 companies working in these spaces. This is about validating the technology. I put peak sales for CAR-T at around $1 billion to $2 billion.

11/ There are about 50,000 patient per year with B cell lymphomas and another 30,000 with Multiple Myeloma. Even if they can capture 10% of them at 8,000 patients, you can get to $1.6 billion based on CAR-T pricing.

12/ When you look at the $1.6 billion potential, the early NK iPSC, the $500 million plus cash, and the future potential for many new targets, this company looks cheap at only $1.5 billion market cap.

13/ I think, when you pare this with the iPSC NK programs, you have a set of technology that is very attractive for a buyer. There are countless CAR-T and CAR-NK targets they can develop for cancer.

14/ They just entered phase 1 with CB010. We should see data read outs in 2021. This will make it able to differentiate from other programs.

15/ So far all allogeneic programs are showing good efficacy and safety, but short durability. Even $CRSP is right in the middle of the pack for average.

16/ I don't think there is anything that prevents $CRBU from moving outside of cell therapies into gene editing like other companies. The biggest reason is patient limits.

17/ In a genetic disease, you have a patient pool who have the actual disease. The number of new patients each year is usually much lower like 1 to 20 per 100,000 people each year. That means every patient cured is removed from the pool until you only have the new patient rate.

18/ Cancer will never be cured. You will always have 2 million new cancer patients diagnoses each year in the US with over 600,000 deaths. There is an endless supply of patients. From a profitability standpoint, that makes Cancer the indications that keep on making money.