It’s my pleasure and honour to be here and I’m very appreciative of the opportunity to present this data to the group. One of the really exciting themes in hematologic oncology right now is the ability to selectively inhibit important pathways for cellular biology. As we have developed tools to selectively inhibit those pathways the theme right now is to combine agents together so that we can both dampen down on parallel pathways for cell growth or to inhibit mechanisms of resistance. Cerdulatinib, which is a dual inhibitor of both the SYK pathway as well as the JAK pathway is able to accomplish this with a single molecule. Today on behalf of my colleagues I’ll be giving you an update on an abstract that will be presented on Sunday in the morning and the full data will be seen at that time.
The purpose of this research, which is a phase II multicentre open label study, was to investigate an oral medication, it’s a competitive ATP inhibitor, as we mentioned, of SYK and JAK. The name of the drug is cerdulatinib and it inhibits two different pathways that lymphoma relies on for survival. The pathways that this specifically targets include JAK1 and 3, SYK and TYK2 and the purpose of the research was to determine not only the safety of the molecule but also its effectiveness in specific subgroups of non-Hodgkin lymphoma.
This phase II study preceded after an initial phase I first in human study had identified the safety and dosing. It was an open label study and it accrued patients who had relapsed and refractory CLL and SLL, follicular and indolent NHL and a T-cell lymphoma cohort that was just opened based on work done by one of my colleagues when he was at the Mayo Clinic looking at aberrant expression of SYK in T-cell lymphomas. Cerdulatinib is an oral medication, it’s taken twice daily at a dose of 30mg in the current phase II study and it’s continued until either progression of disease or toxicity.
What we’ve been able to demonstrate with the results of the research is that at a dose of 30mg b.i.d. cerdulatinib inhibited the pathways of interest, so both SYK and JAK are inhibited at maximal amounts at physiologically obtained doses at 30mg b.i.d. The study initially had accrued patients at 35mg b.i.d. and that dose was then adjusted to 30mg b.i.d. based on analysis of the pharmacokinetics and safety profile. I’m happy to say that that adjustment has reduced some of the incidence of side effects that we saw and has maintained effectiveness.
The effectiveness that we have seen overall in the cohort is that 50% of patients out of a total of 47 accrued to date have had a response. They’ve predominantly been partial remissions with a singular CR at this time point. Of note, in CLL and SLL, where we know that the B-cell receptor pathway is important for the survival of the tumour cells, the response rate is 67%. As with other agents that target the B-cell receptor pathway we do see lymphocytosis, an elevation in the lymphocytes. In follicular lymphoma the response is 56%, so five of nine patients. These responses are brisk, patients feel better quickly, after just two cycles we’re seeing an improvement and, as we mentioned, they’re predominantly partial remissions but they’re sustainable. So at this time point just about 50% of the patients remain on study drug and we have four patients who are approaching one year with disease control and good tolerability.
The most frequent side effects that we have seen are fatigue, diarrhoea, which occurs early and responds well to a dose reduction and antimotility agents, nausea and some cytopenias.
In conclusion, cerdulatinib is an orally available dual inhibitor of two pathways, both SYK and JAK, in a single molecule. We’ve seen consistent activity in relapsed and refractory CLL, SLL and follicular lymphoma with notable responses of 67% in CLL SLL and this cohort continues to accrue, as well as in follicular lymphoma with five of nine partial remissions for 56% and again continuing to accrue. The aphorism that it’s always good to be the first patient on a clinical trial cohort remains true, our first T-cell lymphoma patient achieved a complete remission and is proof of the principle that the biology suggesting that SYK is aberrantly expressed in T-cell lymphomas and may have an important role in its pathogenesis holds true. Responses, importantly, have continued to improve over time with seven out of nine patients having further reduction in their nodal mass on their second and third scans as they continued on study drug. We expect by year end to have additional information on the 30mg b.i.d cohorts in SLL, CLL, follicular and indolent lymphoma and T-cell lymphoma.
With that let me conclude and take any questions. Thank you.