On behalf of my co-authors I wanted to thank everybody for allowing me to present our phase I data to be presented this afternoon, BLU-285 in patients with advanced systemic mastocytosis. Just to give a little bit of background, mastocytosis is an uncommon disease, many of you have seen patients or have heard of people as most patients will have recurrent allergic or even life-threatening anaphylactic reactions. But in addition to that patients can develop proliferation of their mast cells that can invade various organs and patients can present with either indolent disease or smouldering disease but when these infiltrative processes start to cause debilitating symptoms and/or organ damage we consider that to be advanced or aggressive systemic mastocytosis. Those are the patients that were enrolled on the study and those are the patients who unfortunately have a diminished overall survival.
BLU-285 is a highly potent and selective targeted agent against the mutant form of c-Kit, specifically D816V. In fact, it has a more potent inhibitory effect on the mutant form of Kit as compared to the wildtype and if you look at the kinome map, this is a map of the kinases that we have in the human body, you can see that BLU-285 is a more selective inhibitor of Kit as compared to the multi-kinase inhibitor midostaurin that was recently approved this summer, at least in the United States, for patients with advanced systemic mastocytosis based in part on the complete and partial remission rate of 17%.
The study design is a phase I classic study design. I’m reporting this afternoon on the completion of the phase I dose escalation for 32 patients. The primary objective was to achieve a maximum tolerated dose and a recommended phase II dose. Then the secondary objectives were to look at the pharmacokinetics as well as the efficacy endpoints. BLU-285 was administered as a single once-daily dosing and currently we’re enrolling patients in the part 2 dose expansion in the various subtypes or histologic subtypes of mast cell disorders. Treatment emergent side effects were mostly grade 1 or 2; the most common grade 3 non-hematologic toxicity was periorbital oedema which is some swelling around the eyes, very common in other tyrosine kinase inhibitors like imatinib, and fatigue was the second most common non-haem toxicity. Hematologic toxicities were very mild to moderate; all of the toxicities could be ameliorated by either a dose delay or break and/or dose reduction. Given the fact that there was very little toxicity and there were no deaths on study, 30 of the 32 patients that were enrolled on the part 1 remain on protocol and remain on drug. There were only two patients that came off, one because he had progression to leukaemia, and this is a patient who had the concurrent mastocytosis with associated hematologic neoplasia and it was the second disease that took off, and a point investigator withdrew the patient when it was discovered that they were wildtype Kit. No patient discontinued this part 1 of study due to toxicity concerns.
Just a second, because this is an uncommon disease, so when you’re looking at response criteria in terms of mastocytosis or other mast cell disorders the IWG has published their recommended response criteria and a complete remission includes reduction or elimination of the mast cell burden, including the C findings which I alluded to. These are C findings which are representing the organ damage that is from mast cell proliferation and infiltration whereas partial remission includes a 50% reduction in the mast cell burden and resolution of one C finding and then clinical improvement is one or more of the response criteria without a formal complete or partial remission.
If you look at the eighteen patients who had measurable IWG-based response, the overall response rate was 72% with a complete and partial remission of 56%. Many of these responses are ongoing, as all patients with the exception of the two I mentioned are on therapy. In fact, seventeen of these eighteen patients still remain on therapy so we expect this to improve.
In conclusion, I believe that BLU-285 has potent, clinically important activity in advanced systemic mastocytosis. This study validates the target. Selective targeting of the Kit D816V is well tolerated and, in fact, 30 of 32 patients remain on study with a recommended phase II dose of 300mg/day. The overall response rate was 72% at an early look, I would say, with 56% complete and partial remission which is very comparable to the 17% seen in midostaurin. Additional development is ongoing, the drug is now referred to as avapritinib and there are future phase II studies planned next year, both in advanced systemic mastocytosis, mirroring the protocol I just showed you, as well as in indolent and smouldering mastocytosis. With that I’ll end. Thank you.