Dual BCMA/CD19 CAR-T Cell Therapy AZD0120

AZD0120, a dual BCMA/CD19 CAR-T Cell Therapy

There is a new CAR product, that was called GC012F. And this was originally developed by a group in China. Doctor Juan Du has led some of the trials there. And now it's been partnered with AstraZeneca and they have their own number for it, and are starting to develop it in, larger trials in the US and other countries. So it's somewhat unique in a few ways. Number one, it does have two targets. So it hits both BCMA, which is the target of all the other current CARs but also hits a molecule called CD19. And CD19 is a molecule that is the target of CAR-T cells in a lot of other diseases like lymphoma, certain leukemias, CLL, and has been explored in myeloma in some small studies, but it's not expressed on the majority of myeloma cells. But the idea is that there may be a subset of myeloma, precursors or myeloma stem cells that express CD19. And so the thought is, if you hit BCMA on most of the myeloma cells and maybe hit CD19 on that subset or precursors, you might eradicate more of the myeloma clone and lead to better remissions. And so that's the rationale. The other thing interesting about that, CAR product is what's called a fast manufacturing, that they're able to actually manufacture the CAR-T cells in just a few days and, and therefore get it into patients within a couple of weeks, as opposed to maybe that's 4 to 8 weeks that we have to currently wait. So you might get it faster. That also may lead to perhaps a little bit healthier T cells, because the T cells are not having to replicate in vitro in the test tube for a longer period of time, and maybe having some better features of the CARs when they're going in. So that's the design of the product and what makes it different. Otherwise, though, it's like most other CAR products, you still have to collect T cells from the patient, you have to manufacture it, and then you're infuse it after three days of fludarabine and cytoxan. And in some early trials in China, it actually showed very impressive, response rates in a phase one study in relapsed refractory patients. Almost all the patients respond in close to 100% in the median progression free survival is about 38 months. And that's similar to what was seen in CARTITUDE 1 with cilta-cel. It's also been given to even newly diagnosed patients, very small population trial. They all got, I believe, VRd induction and then the CAR and it seemed to be safe in that setting with, again, very high response rates. And, we’re waiting for a longer follow up. So I would say stay tuned. It looks promising. They have not seen any of the delayed neurotoxicity, like the parkinsonism or, or cranial nerve palsies that have been seen with some of the older car products. So I think that's promising as well. And so AstraZeneca is partnering with them. They're opening some studies in relapsed refractory patients in the US and Europe, I believe, and they're I believe thinking about an upfront trial too. So stay tuned. We need to know a lot more about it. But it looks interesting.

Does it target two things at once?

It's a bispecific CAR. So it's a single molecule on the surface of the cells. And it can hit both BCMA and CD19. There are different ways to hit two targets. With CAR-T, you can pull two different CAR products at each hit a separate target, or you could infect the cells so that they have two CARs on the surface, or you could have one CAR that hits both targets. And I believe this one hits both targets.