Beam Therapeutics Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Thanks, John. Thanks, Yanan. Thanks for having me.

Yes, sure. Beam is a platform company developing a really novel and innovative technology called base editing. Here we are doing genetic correction of genes at the single letter level. We use CRISPR to target flexibly within the genome, and that is a quite powerful system. If you change the guide RNA that does the targeting, you have an entirely new mutation that you can target using the same machinery. But then, unlike old CRISPR, we do not make double-stranded breaks, so we are not editing by cutting the genome. We are editing instead by using a deaminase to do single letter changes, so very precise modifications. That gives us the power and the uniformity and the predictability of modifying the genome one letter at a time. We are using this in a wide variety of different places, delivering to blood.

We are treating sickle cell disease, initially ex vivo, with our risto-cel product. That will eventually, hopefully, move in vivo over time. Then in the liver, using lipid nanoparticles to deliver. We are treating alpha-1 antitrypsin deficiency, a very high unmet need disease where, again, a single letter misspelling causes the disease. It is a perfect application for base editor to go in and change that one letter. Then we are looking at other metabolic disorders, including PKU, GSD1A, and others, where again, we are going to go in, find single letter misspellings, turn them back to normal with the base editor. All of these treatments are potential one-time functional cures for these patients so that they get the therapy and that is it. They shouldn't have the disease anymore if we have done our job.

Broadly consistent. We gave a top-line version of this data earlier in the year, in April/May timeframe. This was our first visit to an academic conference, so now communicating with the investigators and the treating physicians in this field. I think major headlines are drug continues to look like we are getting patients into that functional cure zone that we want. So we are getting patients above what is called the protective threshold in alpha-1. The disease is characterized by a deficiency in this protein, alpha-1 antitrypsin. Patients are living in the mid-single digits for their micromolar levels of this important protein, and this important protein is needed to protect your lungs from degradation. We are getting patients into the mid-teens. Every patient is at or above this protective threshold, which is 11 micromolar.

Where that comes from is we know that there are no patients who have this disease who live at 11 or above. They are all in the single digits. So we know we have relieved that issue. Today, we basically were able to give a thorough summary of the dose escalation phase, part A and part B, with single-dose treatment. We are showing now durability of these effects across 18 months or more with these patients. So consistent with that idea of this is a one-time intervention. We are showing dramatic reduction of the toxic protein, the Z protein, over 80%. We are now able to show additional functional parameters. So we had functional data in today's update showing that the AAT that we are producing, the normalized form, it is called the M protein, is fully functional. We showed that. We also showed a reduction in human neutrophil elastase, which is a measure of this potentially problematic process that we are lowering by having the protective M around.

We also showed a reduction for the first time in Z-AAT polymers. Z is commonly thought to be a problem in the liver. It builds up to toxic levels and causes liver toxicity. But unfortunately, when it is secreted, it also polymerizes in the body, and those polymerized forms can also cause systemic damage. They cause inflammation. They also interfere with alpha-1's ability to inhibit elastase activity. All of that data set is now really coming together to show the strong functionality of the blood we are producing. In general, we are getting over 90% M and under 10% Z. The shift from an all Z patient to now dominantly an M patient is quite dramatic.

All of that came together into the update today.

Yeah. A little bit of both. Our original report, I think, for 60 milligrams was in the 12 and a half range, right? Then we were at 16, now 14 and a half. I think, first, this is a protein that moves around. There is a fair amount of up and down in levels in patients. We are also mixing multiple different assay formats. Today's update was in turbidimetry, which is the classic thing that investigators are used to. For an academic conference, we felt that was appropriate. But last time, that 16 number was with LC-MS. It is just a different assay. That will ultimately be the thing we also use for filing with the FDA because it is a quantitative assay. It is also what we use when we want to discriminate the M and the Z forms, okay?

All of that together said, I think at the end of the day, we think this is the same data. We're clearly in the mid-teens. Every patient is at 11 or above. I don't think there's a meaningful difference between 14 and a half and 16, and I expect these numbers to continue to fluctuate over time. By and large, the level we're reaching looks very durable, and I expect it to hold.