My name is Rakesh Popat and I'm a haemotologist and associate professor at University College London in the UK. At EHA 2025 I've been presenting the first results of a first in human study of a novel trispecific antibody known as JNJ5322 for patients who have multiple myeloma that has relapsed. So what we know is that in the real world some of the outcomes for patients with relapsed refractory multiple myeloma aren't so good. And as a result there's been the development of bispecific antibodies and these are drugs such as teclistomab or l-ranatinab and talcratomab. And these are agents that bind the myeloma cells and the T cells and have been shown to be very effective for patients with relapsed myeloma. But unfortunately what we do know is that about 30 to 40 percent of these patients do not respond to these antibodies. We also know with talcratomab whilst it's very effective it does cause some other problems such as oral problems, it interferes with taste, you get a dry mouth, can get skin problems and nail problems. And this is due to the off-tumour binding of the antibody to other areas in the body. This is why we developed a trispecific antibody. What the trispecific antibody does is that it binds to two different targets on the myeloma cell namely BCMA and GPRC5D and its third arm binds the T cells through CD3. The binding is very tight onto the myeloma cells but the binding on the T cells is quite low, it's been dumbed down. The reason for that is to reduce the side effects known as cytokine release syndrome just to make it more tolerable for patients. So the whole reason for this is that the molecule can bind to a myeloma cell that has one target, it could bind to a myeloma cell that has the other target but importantly it can bind to a myeloma cell that has both targets. Now the reason why that's important is that it improves the specificity of the antibody so it homes in just to those myeloma cells and doesn't hit targets around the body elsewhere because those other targets are the ones that cause the side effects namely the mouth problems, the taste problems, the skin issues. So we ran a first in human study, we investigated what the best dose was and we also looked at trying to give this drug as an outpatient unlike the bispecifics where you have to come into hospital. Essentially what we showed was that the toxicity profile was quite good, we showed that the oral side effects were much more reduced, only six percent of patients suffered weight loss whereas with talcumab the bispecific 30 percent of patients suffered weight loss so this is a much better side effect profile that we saw. The cytokine release syndrome was also quite well manageable at about 50 percent and in the outpatient where we give a prophylactic drug called tocilizumab it drops right down to 20 percent so that's only two in ten people who get this cytokine release syndrome. In terms of how well this drug works well at the recommended dose all of the patients that we treated responded, that's a hundred percent response rate and over 90 percent of patients achieved a 90 reduction in their myeloma burden and 70 percent of patients achieved a complete response. In terms of how durable these responses are well so far we've only followed them up for about a year but 95 percent of these patients are still alive and disease progression free at 12 months which really shows the remarkable effects. So in summary this is a highly effective trispecific antibody hits two different myeloma targets as well as the T cells. The tolerability profile appears to be at least as good if not better than the bispecific antibodies and the response rate was 100 percent with almost all patients alive and progression free at 12 months into the treatment. So really this is now competing up with CAR T cells in terms of how effective this is but it has the advantage of being an off-the-shelf drug that you can give with just one dose every four weeks. We're going to be studying it in larger phase three clinical trials coming soon. Thank you for listening.
HealthTree • June 19, 2025