REGN5458 Bispecific Antibody | Naresh Bumma, MD | IMS 2022

Hello, my name is Nourish Brahma. I'm a hematologist specializing in multiple myeloma. I work at The Ohio State University Comprehensive Cancer Center and I would like to talk to you guys about the bisphosic antibody Regeneron 5458. We have presented some very exciting data here at IMS 2022 and I would like to share that with you. So to start off first, what is a bisphosic T-cell-lingager antibody? So I want you to think of it that there are two antibodies that are linked together by a chain. One of them is going to be against CD3 which goes and engages a T-cell and one of them is going to, in this case, will be against BCMA which is a surface marker found on myeloma cells. Now what that does is that it connects those two cells and together and the goal of it is to activate the T-cells which then becomes active, recognizes the myeloma cell and kills it directly. And that approach has been used in other diseases as well and it's getting a lot of traction in multiple myeloma. So there are multiple different compounds with a very similar mechanism of action that are available under investigation and the one that we'll be talking about is Regeneron 5458. So this is a antibody that is infused intravenously. We do this in the IV every week for 16 weeks and then every two weeks afterwards till disease progression or till the patient decides to come off the treatment. The first two doses are given in the hospital and it is a step-up dose and the reason for doing that is that we want to mitigate the risk of a condition called cytokine release syndrome. Now what is cytokine release syndrome? So as if you remember I mentioned that we activate T-cells and that causes your immune system to wake up. Now in some cases it can wake up a little bit too much and become extremely active and causes cytokine storm that presents with symptoms such as fevers, chills, riggers, low blood pressure and so on. So with to prevent that we use the step-up approach given two doses in the hospital. So in this study what we found is that in a heavily prudent population and the majority of patients in this study had at least five prior lines of therapy we had a very good response rate with every overall response rate of 51% and as we went higher on the doses we found that the response rate was significantly improved to up to 75% and out of those more than 60% had a very good partial response or better and four out of ten patients were found to be MRD negative. Now in terms of safety data what we saw is that the risk of CRS in this specific cohort of 73 patients was only 38% which is much better than a lot of the other by specifics that are out there. If you look at the neurotoxicity signal which is also seen in other conditions we've seen only three cases of grade two neurotoxicity and no grade three or grade four neurotoxicity so that was very encouraging to us. We did however see some infections for which we have amendment protocol to take measures to prevent. So this is a very it causes safe and early and deep durations in patients who relapse multiple myeloma and this new therapy will hopefully be studied more in a phase two study and in combination with other therapies and will become part of the treatment for multiple myeloma very soon.