Thread by @Biotech2k1

Taking a Look at #CRISPR gene editing:

This has been a space that really needed new technology after decades of older technology failing to work. The need for precise edits without off target effects still exists.

1/ The top pick here is clearly $BEAM with their base editing technology. They are using a modified CAS9 that only has 1 cutting domain. This allows them to use a deaminase to modify a single base and cut the opposite strand for repair.

2/ This technology has limitations as it can only do ABE and CBE modifications. It can't do insertions. There is still a ton of potential across hundreds of genetic disorders for this technology. They could do billions in revenues if the science works.

3/ This company is still extremely expensive at nearly $4 billion market cap with no human data at all. Along with the significant limitations to the editing technology with delivery, it seems very bubbly.

4/ The next up is $VERV as a base editor, but I would rank them somewhere near the bottom on the fundamentals. They license all their technology from $BEAM and Beam gets a large part of their sales. No reason to own them over $BEAM. If you own Beam, you get $VERV for free.

5/ I don't think any of their indications in cholesterol or triglycerides will ever make much money. There are already many very good therapies in this space. I doubt many patients will opt for such an extreme and untested therapy. I suspect their sales will be very small.

6/ Next up is the top name in the original CAS9 editors with $NTLA. They lost the patent battle so a bit of uncertainty overshadows the company. They have a top quality management team and are leading the innovation.

7/ I think they have a ton of potential if they can put the patent issue behind them. They have outstanding data in ATTR and multiple programs going on in early development.

8/ I think the company is massively overvalued at over $5 billion with only early phase 1 data. This company should probably be worth about half this valuation based on the level of validation of their science.

9/ The next original CRISPR company was my first owned company with $CRSP. They have an outstanding program for SCD. They are in later stages of development and approaching commercial. It is a very big indication, but manufacturing capacity will significantly hinder sales.

10/ I stopped owning this company as they have fallen way behind on the innovation curve. Their CAR-T programs are some of the worst in the business, and I doubt their Diabetes therapy will ever work in its existing form.

11/ The company is definitely cheap if I am wrong about their lack of good innovation beyond SCD. $VRTX already owns 60% of those revenues for the SCD indication. At nearly $5 billion valuation, I just don't find it exciting enough to own anymore.

12/ Next up is $GRPH which I will just come out and say I have thought this was a complete waste of money since the IPO. Their data is really weak and their management seems even weaker.

13/ Last up is $CRBU which is only focused on Cell Therapies. I actually have them as one of my spec cell therapy companies. They have some things to like with their iPSC programs in NK cells. Why they haven't gotten into in-vivo gene editing escapes me.

14/ I will close with one comment that is true about all the CRISPR companies. They are all into the cell therapies space. They all have some kind of CAR-T or NK cell therapies going on. They are all following the science and not leading the science.

15/ I doubt many of them will amount to anything in the cell therapies space. It would be like asking your doctor to give you the worst possible treatment with the weak data and technology these companies are deploying. I hope someday they will get serious in this space.

16/ The potential for combining #CRISPR with #iPSC technologies could be the science that changes the future. The #CRISPR companies only seem to get half of that vision. Some are doing better than others like $BEAM and $NTLA.