Updated Etentamig (ABBV-383)

So ABBV383 is a bispecific T cell engager that targets BCMA, which is still not currently FDA approved. It's still on clinical trials and it's been tested in patients who have had more than three lines of therapy and have been exposed to an anti-CD38, a proteasome inhibitor and an immune modulator. And it's very unique compared to all of the other bispecific T cell engagers in multiple myeloma that target BCMA, which I think we have five right now, two that are FDA approved and three that are in clinical trials. It's unique because it's the only bispecific that we have in clinical trials or commercially doesn't require step-up dosing and that it's dosed once a month from the get-go. So that's one unique thing. So you don't have to be worrying about being in the hospital for a week or seven days or ten days, depending on all the step-ups that the drug has and monitor for CRS. This is a one dose. With the first dose, you get the therapeutic dose and you stay in the hospital for just 24 hours and then you get discharged and your next dose is four weeks later. So with the first dose, you're already getting the therapeutic dose, which is a great benefit, especially for those who don't want to be in the hospital for a long period of time. But the other unique feature about this bispecific antibody is that it is designed in a way that the way bispecifics work is that it has two binding sites or two arms, like I like to say. One arm binds to the myeloma cell and the other arm binds to the T cell or the CD3 portion of the T cell, which is part of the immune system. And then once it's bound to both, it activates the immune cell, the T cell, to destroy the myeloma cell. That's how a bispecific works. But when you have too many of these antibodies in the body and continuously are activating the immune cells, the immune system gets tired and we call that T cell exhaustion. And then once the immune system gets tired, then it stops working because it doesn't have the partner to do the destroying of the cancer cell. So ABBV was designed in a way that it doesn't bind to that immune cell or the T cell permanently. It has a low affinity to that T cell. So what it does is that it grabs it and then it releases it and then it grabs it and then releases it and it grabs it and then it releases it. So it doesn't have it grabbed all the time and activated all the time. So then the immune system doesn't get tired that easily. So we're seeing less T cell exhaustion by doing low CD3 affinity, which can actually it has some advantages. One of them is it causes less CRS, so cytokine release syndrome, because you're not activating the immune system continuously at such high concentration. But then the other thing that it does is that it reduces the likelihood of T cell exhaustion, which makes the immune system continue to work for a longer period of time and in theory could translate into having a more durable effect without affecting your ability to have a good immune system. So those are the unique features of ABBV383. So in addition to the regular clinical trials where all of the other bispecifics have already are participating in those who are triple class exposed and more than three prior lines of therapy, we're currently using this bispecific in people who have had one to three prior lines of therapy and we're soon going to be studying this as part of transplant ineligible patients or as maintenance after transplant or in earlier lines of therapy in combinations. The overall response rates that we're seeing are similar to all of the bispecifics. It's hard to say that one is better than the other because there's no head to head comparison, but in every clinical trial has different criteria to be included in the study, whether you have a certain amount of detectable M protein or free light chains or your kidney function has to have a certain creatinine clearance or your hemoglobin has to be a certain point. But what I can say is that the response rates that we're seeing with ABBV as a single drug is similar to the other bispecifics and the responses that we're seeing in combination, which have already been tested with pomalidomide and diryatumumamab, are showing very similar responses to other bispecifics that are BCMA directed that have been tested in combination therapy. Across the class of BCMA bispecifics, I think the responses are very similar. The thing that makes one unique compared to the other is what I mentioned, no step up dosing and just once a month dosing.