I wanted to just share a few highlights from the recent ASH 2025 Conference. This was a really exciting conference in the space of myeloma and I want to start in particular with one highlight which was a presentation of early data from a phase I clinical trial called inMMyCAR which was actually an in vivo CAR therapy with a BCMA-targeted CAR. The data reported was on four patients, early data but all four patients achieved MRD negative responses and all patients remained also in response at the longest follow-up that they had so far, which was 4-5 months. These were patients that had had multiple lines of therapy, high risk cytogenetics. The tolerability seemed to be very good, there was only low-grade CRS and no ICANS, no [??] and neurotoxicity and also limited cytopenias and no treatment-emergent infections. The authors also showed very good expansion of the CAR T-cells and the memory phenotype, which we know is important, and they showed that this phenotype was actually persistent in blood and in bone marrow, which really portends for hopefully good durability. So, again, early data, very exciting. We had seen some similar results from another trial, also early data, I think it was earlier this year. So really what this is indicating is that maybe we’re starting to crack the code how to make these in vivo CAR therapies work. This could, of course, be a tremendous advance for patients because it overcomes a lot of the limitations of our currently approved CAR T-cell therapies such as the complex process required for production, the potential of manufacturing failures, lymphodepletion is required, cost and access. So very, very exciting data.

I’ll stay with multiple myeloma and mention another trial that is very likely going to be practice changing. This is the MajesTEC-3 trial, a combination of daratumumab and teclistamab. It was a randomised trial for relapsed/refractory patients who had received 1-3 lines of prior therapy and randomised against dara/dex with either pomalidomide or bortezomib. This was a study that met its primary endpoint of progression free survival and also had really encouraging overall survival signals. This hasn’t yet come to full fruition yet but they looked at the overall survival at three years with around 84% for the tec/dara arm versus 30% for the SOC arm. So very encouraging. This type of therapy, of course, with a CD38 antibody and a bispecific, there is some risk of infections, however, what was shown in this study was that that could pretty much be mitigated with good antimicrobial prophylaxis and also with IVIG, with immunoglobulin and monitoring and then IVIG to reduce the infection risk.

I should also mention that there is another ongoing study that is looking at the daratumumab/teclistamab combination with Revlimid in the front-line setting, that’s the MajesTEC-7 study. So it's going to be interesting to see that read out.

There’s more happening in the myeloma space, I will mention that the approved therapy cilta-cel, or Carvykti, we saw some nice data for long-term progression free survival benefit from the CARTITUDE-4 study which is basically looking at patients in earlier lines of therapy, again we are also looking at 1-3 lines of therapy here. So a significant improvement in progression free survival versus control and, again, these authors showed here also, similar to what we saw in the in vivo setting, that with earlier lines of therapy there’s a better fitness of the CAR T-cells that are being produced, stronger immune effects. So something that really makes the case that this is a therapy that will have increased benefit if it’s being used earlier in the therapeutic regimen.

We saw exciting data also for two other CAR Ts in the multiple myeloma space – anito-cel from the ongoing iMMagine-1 study. This is a pivotal study in relapsed/refractory multiple myeloma with 97% overall response rates, very good, again, tolerability, no delayed neurotoxicities and also generally very, very good tolerability. So this is a therapy that hopefully is well on the way to move towards being available for patients.

Then, very exciting, another CAR T that showed 100% overall response rate. Still relatively early, this is a phase I, data from phase I trials, with something called the FasTCAR or AZD0120. This is a dual CAR targeting BCMA and CD19 and, interestingly, this has a very fast manufacturing protocol with next-day manufacturing. Again, very, very high response rates, very high MRD negativity as well and very good tolerability, no neurotoxicity seen, CRS again relatively low grade – grade 1 and 2 – and responses also again in high-risk patients.

I will move on and tell you a little bit about CLL where we had also some interesting data being presented in the plenary session - results from a phase III study, the CLL17 study were shared. That study compared a fixed-duration venetoclax-based treatment with venetoclax/ibrutinib or venetoclax/obinutuzumab with continuous targeted treatment with ibrutinib. This was a study in newly diagnosed patients, really the first true comparison of such a fixed duration – oral doublet therapy against continuous ibrutinib. The goal of the study was non-inferiority, that was demonstrated. The three-year progression free survival was very comparable, some very deep responses were being seen, in particular also MRD negativity for the venetoclax/obinutuzumab combination. So this is, of course, something exciting because time-limited therapies are something that’s highly desirable for patients and having the possibility for patients to choose this type of therapy is going to be something important for the future. Various additional exploration, additional studies ongoing such as the FLAIR study as well that are looking at how long this treatment duration actually should be. In this study it was one year but the FLAIR study it may be two years, so there’s additional ongoing work to really look at what should the duration be.

Now, also for CLL we’re seeing the next generation of the non-covalent BTK inhibitor pirtobrutinib moving forward into the up-front setting. There was an interesting study being presented, the BRUIN CLL-313 study, that actually looked at pirtobrutinib compared with bendamustine and rituximab, again in front-line therapy. There was significantly improved progression free survival over 24 months, so a really good outcome and one of the largest treatment effects that’s ever been observed with a single agent, with a single BTK inhibitor, against this comparator. So this is the non-covalent inhibitor, of course we have the three covalent BTK inhibitors that are already approved. We also recently saw the full approval for pirtobrutinib for patients who had previously been treated with a covalent BTK inhibitor which expands the accelerated approval we had before to earlier lines of therapy. So, again, we’re going to be seeing how this agent will now be used in second line but potentially also moving into first line which, of course, raises the question how potential first-line use will impact the next line in therapy, can you still use a covalent inhibitor after the non-covalent inhibitor? On the other hand, pirtobrutinib has a very, very good tolerability and there may be patients who maybe are just going to be requiring one line of therapy and where this will be an excellent option. So definitely something that will impact practice.

I will mention a trial in AML, also practice changing and also shared during the plenary. This is the PARADIGM phase II randomised study that compared azacitidine/venetoclax to conventional induction chemotherapy for newly diagnosed AML fit patients. So, of course, we know since [??] azacitidine/venetoclax has been the [??] approved option for patients not fit to receive intensive induction chemotherapy. This trial, again, met its primary endpoint looking at event free survival, which was actually significantly improved. The response rates, overall complete response rates, also improved. Overall survival data is continuing to mature but we’re also seeing more patients on azacitidine/venetoclax. So fit patients again successfully moving on to transplant, fewer infections and complications, quality of life improved, symptom burden improved, less time in the hospital or the ICU. So definitely a practice-changing study. As we have already seen, many, many other smaller [??] studies and certainly experience in the clinic that patients, fit patients as well, significantly benefit from azacitidine/venetoclax and this study is now providing this with randomised results which will be important also, of course, to inform all the triple combination studies such as with menin inhibitors and many other targeted agents that we see moving forward. So an important study, clearly practice changing and I will leave it at that and close here.