Last Updated 2/21/2023
CRISPR is one of the original CRISPR CAS9 companies. They use the original CAS9 enzyme to do gene editing. Due to the possible risks of using a double stranded break in a person, they have focused on using the technology for editing cells outside of humans like stem cell and T cell therapies. They are the most advanced company in the CRISPR space. Their lead drug CTX-001 for SCD has been submitted for commercial approval in Europe and will be submitted by end the of Q1 2023 in the US. They recently started to advance a broad pipeline of CAR-T cell therapies using CRISPR gene editing. Their early data isn't very impressive, but there is always room for them to improve their edits. They anticipate to move forward their first in-vivo knockout program for ANGPLT3 for cholesterol.
I have followed Sam Kulkarni since 2018. I owned this for a long time, but I started to feel like they were singularly focused on CTX-001 and had stopped innovating for a few years. Now that they are approaching commercial launch, they have shifted focus back to clinical development. They are working on multiple programs for CAR-T which could always improve the data with newer edits. They are improving the SCD program by progressing toward better conditioning. They are moving forward with hypoimmune beta cells for diabetes. They are also looking to advance their fist in-vivo knock out program. Things are starting to pick up so it seems like the old CRISPR Therapeutics is coming back.
Exa-cel is their lead program for SCD and Beta Thalassemia. This works by extracting the patient's stem cells and editing them to flip the genetic switch back to making Fetal Hemoglobin. They treat the patients with Busulfan to get rid of all the old stem cells. Then they treat them with the new edited stem cells. It is a long and extensive process. This has very strong data at producing high levels of Fetal Hemoglobin and eliminating Vaso Occlusive Crisis. This therapy will be submitted for FDA approval soon. They are also progressing with new conditioning with CD117.
CTX-110 is their first CAR-T therapy for CD19. It is an allogeneic therapy where they take donor T cells and edit them before giving them to a patient. These cells don't have any advanced edits, and the data has been very weak compared to other allogeneic CAR-T programs. They have 67% ORR with only 28% responding at 6 months.
CTX-112 is their second generation CD19 CAR-T therapy which includes their new Regnase-1 and TGF-BetaR2 edits which are designed to increase potency of the CAR-T cells. They should be enrolling these in phase 1 soon.
CTX-130 is their second CAR-T therapy. It is an allogeneic therapy focused on CD70 in T cell Lymphomas. They showed 70% ORR rate and 27% responding at 6 months. This still lacks the key immune evading edits and the data is still on par with other allogeneic programs.
CTX-131 is their second generation CD70 CAR-T therapy which includes their new Regnase-1 and TGF-BetaR2 edits which are designed to increase potency of the CAR-T cells. They should be enrolling these in phase 1 soon.
VCTX-211 is their Diabetes therapy they are working on with Vertex. This is the second generation of the islet cells program. I believe these cells have fitness edits, but they still lack the immune evasion edits and will still need the capsule to implant them..
Cash $1868 million
Exa-cel is shared with Vertex with CRISPR getting only 40% of the revenues. I think they could do about 1,000 doses per year to start and maybe ramp from there. At a price of $2.5 million, that would be worth $2.5 billion in revenues. That would be $1 billion that would go to CRISPR. I would give them 3x multiple for a program awaiting approval. That makes this program worth $3 billion in valuation.
CTX-110 is in the space of CD19 which is very competitive. Based on its data compared to peers, I really would not see this making much money if any at all. I gave it a $0 value.
CTX-112 is in the space of CD19 which is very competitive. They don't have any data on this program yet, but it includes the Regnase-1 and TGFBR2 edits that are supposed to improve potency. If they are successful, this could produce $250 million or more in revenues depending on data. I would give that a .1 multiplier since it has no clinical data. That gives it a value of $25 million.
CTX-130 is in the space of CD70. I would guess this could have a patient population of at least 10,000. It would depend on the data on how much market share. I would think this could be worth $1 billion revenues if successful. I would give this a .5 multiplier as it has some phase 1 data. That would make it worth $500 million in value.
CTX-131 is in the space of CD70. They don't have any data on this program yet, but it includes the Regnase-1 and TGFBR2 edits that are supposed to improve potency. If they are successful, this could produce $1 billion or more in revenues depending on data. I would give that a .1 multiplier since it has no clinical data. That gives it a value of $100 million. I would think this replaces CTX-130 revenues and is net neutral.
VCTX-211 is their islet cells for Diabetes. If they can get this to work. I think they could do at least $2 billion in sales for diabetes. CRISPR would only get 50% of those sales for $1 billion. I think the number of patients that would qualify for such a therapy would be only a small fraction of those with a need for it. I give this a multiplier of .1 which gives it a value of $100 million
All in, that is a $5.493 billion market cap. Based on the 78.6 million shares outstanding, that comes to $69.88.
Vertex Partnership for CTX-001 in SCD and Beta Thalassemia which they get 40% of sales.
Vertex Partnership through ViaCyte for Diabetes which they get 50% of sales.
Vertex Partnership for CF, DMD and DM1 with 50% of the sales
Nkarta to develop NK cells with 50% of sales.
Exa-cel Submitted in Europe
Exa-cel On track for US BLA by end of Q1 2023
Phase 3 in pediatric patients continue to enroll
CTX-110 Enrollment and Dosing ongoing
CTX-112 Initiating phase 1/2
CTX-130 Enrollment and Dosing ongoing
CTX-131 Initiating phase 1/2
VCTX-211 Enrollment and Dosing ongoing
CTX-310 Planned to move into clinic this year
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* These are my Opinions and Estimates. They should not be considered financial advice.