Fate Therapeutics, Inc. 12th Annual Cantor Fitzgerald Global Healthcare Conference

Sure. Thanks for the invitation, Lee. As Lee mentioned, I'm the CEO of Fate Therapeutics, and we've been pioneering the concept of using master cell bank for cell therapy. What that does is it creates this really unique starting material for manufacture. I'll explain some of the details here on why it makes it so unique and why we've been pursuing this concept over the past 15 years. Typically, CAR T, which has shown really profound data, is made from either patient T cells or donor T cells, and there are some limitations which we'll talk about. But when you introduce the concept of a master cell bank, now you're making over 10 million doses per the master cell bank, compared to only 500 doses from a donor T cell.

Now you have the capability of creating over 50,000 batches or 50,000 doses in a manufacturing suite compared to where you're limited to a couple of thousand doses with auto or allogeneic CAR T concepts. You're also creating a very uniform product. The starting material is the same every single time, so you have uniformity and reliability. Your cost of goods is down. It's not hundreds of thousands of dollars. It's actually a couple of thousand dollars, around $3,000 a dose. So this concept of being able to produce an off-the-shelf inventory that can be treating patients on demand at a cost-effective manner with reliability, without the need of exhausting your starting material, really gives us a unique approach to generating CAR T.

I would argue that over the next 12 months, we're very excited, perhaps the most exciting 12 months in Fate's chapter, and so we're very excited to talk about what's next there.

Sure. Yeah. We started this whole concept here with safety in mind, and I would call it a planned safety in mind. What I mean by that is at the molecular level, at the manufacturing level, and at the clinical schema level, we really wanted to make sure we had safety first in mind. What I mean by that is at the molecular level, we selected a CAR motif that is tuned for allowing for controlled expansion, but not allowing for uncontrolled expansion. I think that's a key issue that you see with CAR T cells. In addition to that, we put the CAR into the TRAC locus to allow for biological expression of a CAR similar to a TCR and not super physiological levels of expression that could also contribute to uncontrolled expansion.

We completely knocked out at the molecular level, TCR expression, so there is no incidences of GvHD that can be done through the TCR. At the manufacturing level, as I mentioned earlier, we created a master cell bank to ensure reliability and uniformity. So each dose is the same, and you're not going to get a situation where patient 10 gets a dose of CAR T cells that has half a copy per cell of CAR T. On top of that, it has only 20% CAR expression compared to patient 100 who might get five copies of the CAR and really 80% expression. Those two are two different drug products that will result in two different outcomes. So for us, at the manufacturing level, each dose is consistent and is the same with the same expectation.

At the clinical level, we didn't want to go in with heavy conditioning. Three days of CyFlu, and then we'll talk more about that. It is not something that's preferred, and it could also allow for uncontrolled expansion. We're going in with less intensive conditioning or no conditioning at all. At these three different stages, we control safety and we're not surprised by our safety profile that's very much favorable and has very limited incidences of adverse events. We're very proud of our safety because we worked hard to get there.

Sure. We've dosed over 30 patients in autoimmune and over 50 patients previously in oncology with the same product, the master cell bank concept. It is the same product. Nearly 100 patients have been treated in total, and so far things have looked as expected, safe.

Sure. Maybe the latter point first. I think if you have autoimmune disease, you want to get treated as soon as possible as well.

The patient burden that comes with CAR T manufacture is also something that's not desirable. These patients have to come off their current standard of care therapy to procure their T cells, and there is no immediate drug available to them afterwards. You're taking a massive risk by coming off your immune suppressants and possibly allowing for a flare to occur because there is no CAR T that's given to you right after you come off your standard of care. You got to come off, procure T cells, wait over a month to get that CAR T treatment. As an autoimmune patient, you would really want that quick on-demand availability. Going to your first question, as I mentioned earlier, CAR T is very heterogeneous when it's being made with a T cell as a starting point, and that creates unreliability.