Wednesday, December 17, 2014

Galapagos regains full rights to the entire GPR84 program from Janssen as it plans to open Phase 2 ulcerative colitis studies this month

This alert comes from our UpdatesPlus-IBD service.  Providing ad hoc analysis of breaking events as well as detailed reports on IBD drug development this service is rapidly becoming a valued intelligence resource across the R&D community.  To receive a complimentary copy of our most recent issue please contact

Galapagos has announced that it is taking back full developmental rights to this program which includes GLPG1205 and its backup GLPG2384.  No further details were disclosed on the reasons for this decision 

GLPG1205 antagonizes GPR84 and has reported good efficacy in models of IBD as well as good Phase 1 safety, PD activity and favorable drug-like properties.  As a result Galapagos announced in its press release that Phase 2 ulcerative colitis studies will start this month 

Comments: GPR84 is a medium chain free fatty acid receptor found on neutrophils, monocytes and macrophages and contributes to chemotaxis and cytokine release. Antagonism limits disease activity in models of IBD. 

Galapagos reported that Phase 1 data were positive almost exactly one year ago. Data were presented in greater detail at UEG a few weeks ago. Safety was in general good with no treatment related AEs observed in a SAD study. In a MAD study events were absent at 50mg and 100mg but at 200mg 2/6 patients reported dehydration, oropharyngeal pain, vomiting and fatigue. We suspect that the same 2 patients exhibited each of these effects as they are all consistent with vomiting. This needs to be confirmed as does the severity of vomiting. 

Crucially however PD data (below) reports near complete inhibition of receptor binding at the lowest dose test. The difference in inhibition across doses is rather modest suggesting the AEs may be off-target. Thus, even if doses under 200mg are deemed excessive for advancement, Galapagos' back up may be devoid of such activity.

Although Galapagos has not provided further details on Janssen's decision, we do not believe safety/efficacy are explanations. It is probably too early to gain a full understanding of efficacy and as mentioned safety/tolerability appears good at appropriate doses. Moreover, Galapagos has consistently stated, even in yesterday's release that ulcerative colitis studies will open this month. It is noteworthy that yesterday's decision came almost 1 year after the data becoming available and it is possible that a "no-development" clause had been triggered

Janssen has now discontinued two Phase 2 ulcerative colitis assets in rapid succession.  Janssen also handed JNJ-54781532 (ASP015K) back to Astellas at the start of the month. This did not come as a surprise to us given data presented at ACR 2014. These data were issued as part of our UpdatesPlus-Rheumatoid Arthritis service and report a very unconvincing dose response curve. Uncertainty in rheumatoid arthritis, the largest JAK market in immunology doubtless contributed to Janssen pulling out of ASP015K development.  Discontinuing the GPR84 program is more surprising


Post a Comment

<< Home