buffalo1 schreef op 9 juni 2011 13:02:
News:
Galapagos announced the initiation of the phase II program for GLPG0634 (oral JAK1 inhibitor). The first (small) study is intended to show quick onset of clinical response, with results at or just after YE11. Galapagos disclosed that GLPG0634 is the clinical program they intend to partner. No rating changes.
Details and our view:
The phase II study will involve 36 RA patients with insufficient response to methotrexate (MTX). Three groups of 12 patients will receive once or twice daily dosing regimes of GLPG0634 or placebo for a period of 4 weeks, all on a background of MTX. Other –competitive- JAK inhibitors have shown long-term efficacy with an early onset of action. The primary endpoint will be ACR20, the standard primary endpoint in RA trials. Other typical RA measurements will be included as secondary endpoints. The study will be performed in a single Eastern European centre.
Because the small number of patients and the short dosing period, the company is guiding for study completion by YE11 and results publication soon after.
However, given the small patient cohorts, we do not believe the results of GLPG0634 will show statistical significance, but rather may provide a first indication of efficacy and safety of the product.
A thorough safety assessment for kinase inhibitors is in our view very important (JAK = janus kinase). According to Galapagos, GLPG0634 is very selective for JAK1 (the janus kinase family has four members: jak1, jak2, jak3 and tyrosine kinase) and wants to use this characteristic as a differentiation factor versus competitive products. Indeed, Pfizer’s tofacitinib (finishing phase III development) is a JAK3/1 inhibitor (with some activity on JAK2 as well), while INCB28050from Incyte/Lilly is a JAK1/2 inhibitor. Research papers suggest that side effects (lowering of red blood cells) seen with JAK inhibitors may be related to activity on JAK2. This could be the reason why Pfizer did not choose for the highest dose in its final clinical development. Hence, the reason why Galapagos claims that GLPG0634 could be a more interesting compound versus competition because of its higher window of activity versus of JAK2 activity. A better safety profile may allow for higher dosing andultimately result in better efficacy. Note that the chances of showing activity in this study are higher for GLPG0634 versus –the failed-GLPG0259, as the JAK target has already been validated (MK5 wasn’t).
The partnering ambition of this program does not come as a surprise to us (see our previous publications). Oral compounds are considered the next big thing in the treatment of inflammation diseases and several big pharma companies have closed partnerships with small biotech to get access to such products, typically at the phase II level. We understand that Galapagos has received interest for the compound and the results of the today announced phase II trial will not be awaited for to close the deal. The partnering plan is also the reason why the first phase II trial is small, as it will be the partner who has to decide on the full clinical development.
Conclusion:
Timelines, trial design and partnering ambitions are in-line with our expectations. Current trading levels suggest over 25% upside to our € 12/sh target, buy rating maintained.