Beam Therapeutics Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Great. Well, it's great to be here. Thank you for having us. Beam is in a really important phase where we're executing really across a number of different key initiatives in a portfolio that continues to grow and starts to have line of sight to real commercial franchises in gene editing across a number of diseases from sickle cell disease, alpha-1 antitrypsin deficiency, PKU, GSD1A, and others. As you know, of course, we're working on next-generation gene editing technology with base editing. This is a CRISPR 2.0 capable of making single base changes in genes without making double-stranded breaks. We're delivering this ex vivo in sickle cell disease, that's risto-cel, which is on its way to our first BLA filing, and we think has a high probability of success to get approved and be a best-in-class product in sickle.

Then, of course, we do in vivo with lipid nanoparticles delivering to the liver. There, generally, we are taking mutations and turning them back to normal, which is a first-in-history achievement. That'll be BEAM-302 in alpha-1. It will be BEAM-301 with data later this year. PKU, another big indication headed to the clinic soon.

Yeah, it's a great question. I generally think of it as gen 1 was sort of CRISPR ripe out of nature. You use it in its normal way, which is it binds to a certain spot. That targeted binding is a real breakthrough, and it's programmable with the guide RNA. But once you get there, it does its normal thing, which is cut, and you end up scrambling the genome. It's very good at turning things off, but not so good at fixing them. I think this next generation of tools, of which base editing is the first, you mentioned prime editing, and there are others, generally do the precise targeting that we learned from CRISPR, but we turn off the cutting. Instead, when we get there, we're going to do a more precise, controlled change.

In base editing, you do a single base change chemical reaction. In prime editing, you're doing rewriting with the reverse transcriptase, and again, there are others. I think the power of these next gen approaches is now we can really rewrite, reprogram the genome. Now within that class, obviously base editing is the most validated. We've been working on this now for years. We're clear leaders in the field, and base editing works really well. It's highly efficient. It's very predictable. At this point, it's been working in multiple diseases, as we have shown in our data. The next technology with prime, some of these prime systems, we're still waiting for more data. We have some ex vivo data from Prime Medicine, which obviously looks good. In vivo, we're still looking to see some data there.

I would say the validation level of that technology is lower, but hoping to see some more data soon.

In genetic medicine, these are not pills. You cannot take them and get it to every cell in your your body. But we have solved delivery for certain key applications. Obviously the cell therapy process where we take the stem cells out of the body, edit them, put them back in. In sickle, that is now well-validated. We have taken that to a very high level with our manufacturing process. On the in vivo side, lipid nanoparticles, very well understood, but tricky. You have to still have a lot of capabilities and get them right, that is to get to the hepatocytes. A next generation that we will talk more about in the coming years is targeted lipid nanoparticles. This is where we take an LNP, we de-target the liver, and now we retarget it using binders to different cell types.

We have done this for T cells, and we are very hard at work doing this for blood stem cells, which would be the foundation of our in vivo sickle program, which is a next generation program we have in sickle. Bottom line is you have to get delivery right, and you cannot talk about delivery unless you also talk about manufacturing. Beam has spent years building out manufacturing, a full stack. It is all internal. We have a large facility in North Carolina, a tremendous team there. They do all of our cell manufacturing for sickle. They do all of our mRNA production, all of our lipid nanoparticle production. Beam has really built a fully integrated capability from the design of delivery, the design of the editing, to how we manufacture that deliver to patients.

I think that has created a real platform and a flywheel now because we can apply those capabilities over and over again and go faster and faster to diseases 2, 3, 4, 5 and beyond.

Yeah. Alpha-1 is a very large unmet need in genetic disease. You have patients who almost uniformly, over 95% of them, have the same genotype. They have a single misspelling in their SERPINA1 gene, which is for this protein, alpha-1 antitrypsin. It causes a mutant form called the Z form of the protein. We call the normal form M. The Z protein does two things. It builds up in the liver in a toxic way, and it causes liver failure over time. It also is imperfectly secreted and also dysfunctional, so it is not getting enough levels to your body where it is supposed to protect your lungs. When you get sick, your body mounts an inflammatory response. A side effect of that response is it can destroy your lung tissue and give you lung failure unless you have this protein present.

These patients do not have enough of it, and they start to fail with their lungs as well. This is a perfect indication for base editing. We want to go in, we want to land right on that mutation spot, use the base editor to change that letter back to normal, and literally turn a Z allele back to an M allele. We have done this. This is, again, the first time in history we have shown direct correction, a rewriting of a gene to a functional state. Obviously, that has been source of the great enthusiasm for the product. There are 10,000 to 15,000 patients diagnosed in the U.S. alone with this disease, all of whom would be a fit for this product. From there is up to 100,000 total patients.