Last Updated 2/28/2023
Beam is the company behind base editing. This takes the CRISPR CAS9 enzyme system and uses it to alter a single base in the DNA. It uses a form of the CAS9 enzyme called a Nickase. This version of CAS9 is developed with only 1 of the nucleases active so that it can only cut a single strand of the DNA. It uses a deaminase enzyme attached to the CAS9 nickase. This enzyme plucks an amino group from the DNA base. This facilitates the transition of that base from an Adenine to Guanine or a Cytosine to a Thymine. Then it cuts the unedited strand which allows the DNA repair machinery to use the changed base to fix the mismatch of bases after deamination. Beam is the only company that owns this technology. They do license it to other companies for use. Beam is also working on next generation base editors.
I have followed Beam and John Evans for nearly 3 years now. I got into this company right after the IPO and have followed it for years. I think he has done an outstanding job so far developing the partnerships. They have 4 partnerships now that give them very large royalties for any products created with base editing. He is doing an outstanding job for developing the technology. They have multiple indications working toward the clinic for in-vivo editing. He has managed the finances well with plenty of cash on the balance sheet. They are just starting clinical development for their ex-vivo SCD program. It will take some time to know how well they navigate the clinical process and regulatory environment.
BEAM-101 is the first stage of development for SCD. They are extracting, editing and replacing stem cells from patients by editing the stem cells to flip the switch back to producing Fetal Hemoglobin. This is in phase 1 and enrolling patients, but has no data yet. The preclinical data showed powerful 60% Fetal Hb production. The next stage of development is going to combine the first stage with a CD117 conditioning regimen. This is far safer than Busulfan myeloablation. They have to add a single extra edit to the stem cells to modify the binding site for CD117. This allows the CD117 antibodies to clear all the unaltered stem cells while avoiding the newly engineered stem cells. The final stage of this program will move to actually editing the stem cells in-vivo, fixing them to a Makassar variant of healthy Hemoglobin.
BEAM-201 is a CAR-T therapy that is engineered using base editing. It targets the CD7 protein on T cells. This is designed for T cell based ALL. Most of ALL is B cell, and there are many companies working in this space. T cell ALL is one area where new therapies are needed. This is starting phase 1 and has no data yet.
BEAM-301 is a gene editing product targeting the G6PC gene that has a single base mutation. Their therapy targets flipping that single base back to the wild type. Mouse models show modest return to normal fasting glucose. This affects the R83C and Q347X mutation of the GSDIa disease. They plan to submit an IND in early 2024.
BEAM-302 is a gene editing product targeting the E342K mutation of AATD. This is a single base mutation. They have a therapy that attempts to base editing that single base mutation back into the wild type. The mouse models show modest return of normal A1AT protein. There is a by-stander edit in this therapy resulting in a variant of D341G. The data suggests this variant functions normally. They plan to file and IND in early 2024.
Cash $1.1 billion
BEAM-101 is for SCD. There are 90,000 patients in the US and over 300,000 patients world wide with SCD. There will need to be more than one company to service this large patient population with the limited manufacturing capacity these companies will have. I think they could easily do at least 1,000 patients a year and maybe expand upward to 2,000 a year. At a price of around $2.5 million per patient, that is $2.5 to $5 billion in revenues. I would put a .1 multiplier on this program until we see some data. That makes it worth about $500 million in value.
BEAM-201 is for T cell ALL. My best math says this would be about 3,300 patients per year. This is a smaller indication but would afford pricing power and less competition. I could see this doing $500 million in sales depending on the price. I would give this a .1 multiplier until we see some data for $50 million value.
The BEAM-301 program is for GSD1a with the most common mutations of R83C and Q347X. This is about 900 and 500 patients respectively based on the numbers from Beam. That is a smaller indication, but I think pricing would be equal to SCD or higher. I think this could be worth more than $1 billion. I would give it a .1 multiplier since it is still preclinic. That would make it worth $100 million in value.
The BEAM-302 program is for AATD with the most common genotype of PiZZ to correct the E342K mutation. The population for the PiZZ genotype is about 60,000 patients in the US. This could be a huge indication like SCD where they could do upward of $5 billion sales if they can manufacture enough doses per year. I would give it a .1 multiplier since it's still preclinic. That would make it worth $500 million value.
All in, that is a $2.25 billion market cap. Based on the 72.4 million shares outstanding, that comes to $31.07.
Broad Institute, MIT and Harvard licenses the technology for base editing to Beam. They will pay a low single digit royalty for all products made with base editing.
Pfizer for indication is the liver, muscle and CNS. Pfizer retains full world wide development for all of these programs except one. Beam has the opt in rights to one program. This program is split 35% for Beam and 65% for Pfizer.
Apellis has partnership for up to use of base editing in complement related diseases. Apellis is able to license up to 6 programs. Beam has the right to opt into one program and participate 50/50 with them.
Verve has a license for 3 liver targeted cardiovascular related diseases. They get the option to participate in any one of these programs at 35% world wide sales and 50% of the US on the other 2 programs.
Sana has a license to use CAS12 in editing stem cells for their cell therapies.
BEAM-101 Data expected in early 2024
Escape Working toward IND Enabling
BEAM-201 Initiating Phase 1 and plans to dose first patient by mid 2023
BEAM-301 Working toward IND in early 2024
BEAM-302 Working toward IND in early 2024
No Clinical Data Yet.
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* These are my Opinions and Estimates. They should not be considered financial advice.