It’s my privilege also to be here at the EHA meeting to present results on the HORIZON trial which is a really exciting new direction in the treatment of relapsed/refractory myeloma. We know that there are subsets of patients after multiple lines of prior therapy with immunomodulatory treatment, proteasome inhibition and antibodies who remain chemosensitive and actually benefit from chemotherapy. The fact is, however, that chemotherapy carries with it all sorts of side effect profiles that can be challenging and obviously a more targeted approach could be helpful.

In that regard melflufen constitutes a true novel agent. It’s a peptidase activated conjugated target alkylating moiety that is delivered directly to the tumour cell and is remarkable because its delivery to normal tissue in the context of preclinical models is minimal. It is highly lipophilic so it still goes to the bone marrow so myelosuppression is expected but nonetheless non-hematologic toxicity in clinical experiences to date has been minimal which is very encouraging.

So it was these sort of data that spurred the HORIZON phase II study and not least of which was an earlier phase study in which we’d seen relapsed refractory patients see substantial response benefit but also survival in a single arm trial which was compelling. So this next step was a larger multicentre international effort looking at the activity of this drug in an area of exquisite unmet medical need which is the triple class refractory patient population who are relapsed/refractory and in whom proteasome inhibition, immunomodulation and, most importantly, either or both pomalidomide and daratumumab have failed them. So when this has happened we are really in need of some new treatments and the HORIZON study was an earnest effort to evaluate that. What we’ve seen, remarkably, is that in over 120 patients, and the study is still ongoing but this is a preliminary report, that about a third of patients are responding and, most importantly, in that same setting that these are enriched for high risk. Furthermore, clinical benefit rates, minimal response, are better in about 45%, stable disease in even more, approximately 60%. So given that in mind we’re very pleased to see these early results.

I should share with the audience that we’re seeing activity in extramedullary disease which is particularly ominous in this setting and we’re seeing about a third of patients again respond. In the high risk population, of which there appear to be about 60% in those who have evaluable cytogenetics, activity is seen. Side effect wise the myelosuppression is expected but otherwise not much else.

So, again, putting this all together, our take away is that this is very promising for future study. And in that same spirit at this meeting the ANCHOR trial data are being updated and they show in combination with bortezomib a response rate of 100% in a very small number of patients but nonetheless very compelling and in a similar but larger number of patients an 80% response rate to combination with daratumumab. So if this continues to be seen as that study expands that’s a remarkably exciting new direction for our patients.