Thread by @Biotech2k1

@HassanAesthetic Profile for $EDIT

1/ This is the first CRISPR company to start using the CAS12 enzyme. It was formerly known as cpf1 if you ever see that term. It is a smaller structure than CAS9 with CAS9 being about 4.1kb big and CAS12 3.8kb big.

2/ That makes it fit into an AAV vector for delivery and leaves room for other necessary components. The CAS12 enzyme also makes a staggered cut in the DNA which is far more favorable with the repair machinery of the cell to fix the breaks without indels.

3/ They had some challenges over the years with weak management and poor development choices. Early on they wasted a lot of time with trying to do SCD like $BLUE, but their data ended up weak. They ended up abandoning that program and switching to one like $CRSP.

4/ It took a lot of time and a new management to change the focus. Their lead programs are in eye disorders. I find some things to like about targeting the eye and a few that make me more cautious than the liver companies.

5/ The first is the eye has little to no cell turnover. This makes the idea of cancer genesis happening from a single mutation very remote. Cancer takes an accumulation of many mutations over many cell cycles. Without cell cycles, there is little risk of cancer.

6/ You can still see the potential for off target edits from the guides, but the eye is a good place to start from a safety standpoint.

7/ The bad side of the eye is they have to use AAV for delivery which has problems with inflammation and persistence. Its been shown that AAV can stay around for 120 days still releasing the genetic contents. With LNP in the liver, the mRNA is all released in a few days.

8/ They have 2 indications in the eye with LCA10 and Usher Syndrome. These are very rare eye diseases with small patient populations. LCA10 has only about 2,000 known cases in the developed world. Usher syndrome could be as many as 30,000 in US.

9/ The fear with these very small patient population disease is they won't make very much money unless they charge very high prices. If they got 50% of the LCA10 population at $1.5 million, that is only $1.5 billion total.

10/ If you plot that on a bell curve over 8 years of a patient population, it comes out to peak sales of $525 million in year 4 or 5. Usher Syndrome could be much larger if they can get a good size penetration into that market.

11/ Even 10% of the 30,000 patients could be worth $3 billion or more in one time sales. I think they could sustain at least 1,000 of these treatments per year for a $1.5 billion run rate.

12/ There is a lot of potential in the eye with over 350 known genetic eye diseases. It will come down to how well they can edit with AAV in the eye.

13/ I always hear people claim that transient inflammation in the eye with steroid treatment is a short term issue for a long term benefit. Every time one of these companies has data and shows inflammation, the stock tanks.

14/ There has been a lot of disappointment with Gene Therapies in the eye using AAV vectors. Most of it is due to the vector and inflammation.

15/ They partnered away most of their T cell editing therapies. They do have a partnership with Bluerock for iPSC which is really interesting, but I do believe its limited to only a few indications. I think they are too far behind in SCD to even be a competitor anymore.

16/ The thing I like about $EDIT is they are still innovating. They just published data on their new SLEEK platform of editing. They also presented data on CAS12 ultra.

17/ If the data reads out well in the eye, I think $EDIT could be worth $5 billion on the pipeline and maybe $6 billion if you throw in the cash. A lot of value is riding on this first eye data read out.

18/ One good readout for LCA10 should be able to be extrapolated to the other indications for success. It will be the same CAS12 enzyme in the same AAV vector. The only difference with be the gene insertion or knock out and the guide.