Week 12 study results

Transcription

1 Week 12 study results 15 April 2015 Copyright 2015 Galapagos NV

2 Disclaimer This document may contain certain statements, including forward-looking statements, such as statements concerning the safety and efficacy of filgotinib following the 12-week results from the DARWIN 1 and 2 trials and the expected timing and announcement of topline 24-week results from the DARWIN 1 and 2 trials and expectations regarding the commercial potential of our product candidates, all of which involve certain uncertainties and risks. Forward-looking statements are often, but are not always, made through the use of words or phrases such as believes, anticipates, expects, intends, plans, seeks, estimates, may, will, could, stands to, continues, we believe, we intend, as well as similar expressions. Such forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause the actual results, performance or achievements of Galapagos, or industry results, to be materially different from any historic or future results, performance or achievements expressed or implied by such forward-looking statements. Among the factors that may result in differences between the statements contained herein and the actual future results, performance or achievements, are the inherent uncertainties associated with competitive developments, clinical trial and product development activities, regulatory approval requirements and estimating the commercial potential of our product candidates. Given these uncertainties, you are advised not to place any undue reliance on such statements. All statements contained herein speak only as of the release date of this document. Galapagos expressly disclaims any obligation to update any statement in this document to reflect any change or future development with respect thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation. The 12-week results from the DARWIN 1 trial are based on the interim study database, reflect the then available data and respect the blinded nature of the ongoing clinical trial. The data might be subject to changes in light of the 24-week results from the DARWIN 1 trial. 2

3 Galapagos at a glance 5 key aspects 1. Filgotinib: first-in-class oral in RA 2. Transformational CF therapies 3. Fully-owned Ph2 programs in IBD/IPF 4. Platform to fill pipeline 5. Strong financials & partnerships 3

4 Filgotinib, a new mode of action JAK1 discovered by us as target for bone & joint disease compound screening lead optimization development JAK1 discovered using SilenceSelect PCC nomination Start PoC Start Ph2A DARWIN 12w results Start Phase I trial PoC results Deal with AbbVie Start Ph2B 4

5 What are patients looking for in RA treatment? Oral administration Highly efficacious, measured as ACR50 Rapid onset of action Safe & well tolerated 5

6 Courtesy Dr. John J. O Shea, NIH, Bethesda Why JAK1 inhibition? Multiple cytokines 4 JAK family members signal for cytokines and growth factors JAK1 IFNs, IL-6, IL-2, IL-7, IL-15, IL-21, Jakinibs JAK2 JAK3 TYK2 IL-23, EPO, TPO, GM-CSF, GH, IL-2, IL-7, IL-15, IL-21 IL-12, IL-23 JAK1 breaks the vicious cycle in autoimmune inflammation 6

7 Selectivity matters Filgotinib is the selective JAK1 inhibitor 30 Ratio JAK1/JAK2 in human whole blood assay baricitinib decernotinib Xeljanz filgotinib 7

8 Filgotinib is a JAK1 inhibitor First selective inhibitor of JAK1 Novel mode of action for treatment of RA Oral treatment, small molecule Favorable safety & efficacy profile in 4-week studies in RA 8

9 % responders Competitor data ACR responses at W active treatment placebo ACR20 ACR50 ACR70 ACR20 ACR50 ACR70 ACR20 ACR50 ACR70 adalimumab 40 mg EOW ARMADA 2003 tofacitinib 5 mg bid Kremer 2012 baricitinib 4 mg qd Keystone

10 Design Double-blind, MTX background Placebo 25 mg bid 50 mg bid 100 mg bid W12-24 treatment period ONGOING 50 mg qd 100 mg qd 200 mg qd Screening Day -29 to Day -2 W0 W12 analysis primary endpoint W24 analysis 10

11 Objectives Primary ACR20 response of any dose or dose regimen versus placebo at week 12 Major secondary ACR50, ACR70, ACR-N, DAS28(CRP), CDAI, and SDAI compared to placebo up to week 12 safety & tolerability 11

12 Key eligibility criteria Comparable to other studies in moderate to severe RA patients Inclusion diagnosis of RA since at least 6 months (2010 ACR/EULAR criteria of RA & ACR functional class I-III) 6 SJC (66 joint count) & 8 TJC (68 joint count) screening serum CRP 0.7 x ULN MTX for 6 months on stable dose (15 25 mg/week) Exclusion current therapy with any DMARD other than MTX current or previous RA treatment with a biologic DMARD ULN = 9 mg/l 12

13 Largest Phase 2B study in RA Equal group sizes, low dropout rates Screened N=1276 Randomized N=599 Randomized & exposed N=594 Not exposed N=5 Placebo 50 mg 100 mg 200 mg 2x25 mg 2x50 mg 2x100 mg N=86 N=82 N=85 N=86 N=86 N=85 N=84 Discontinuations (blinded): 6.4% for safety: 1.7% for efficacy: 0.2% for other: 4.7% 13

14 Baseline characteristics Demographics & disease 14 qd groups Placebo 50 mg 100 mg 200 mg 2 x 25 mg bid groups 2 x 50 mg 2 x 100 mg Age, mean, years Female 81% 84% 76% 86% 79% 76% 83% Duration of RA, mean, years DAS28(CRP), mean CRP, mean, mg/l TJC68, mean SJC66, mean

15 Patient distribution Geographically balanced Latin America West and Asia-Pacific Central Europe Eastern Europe

16 Primary endpoint: ACR20 at W12 ITT-NRI qd groups bid groups Placebo 50 mg 100 mg 200 mg 2 x 25 mg 2x 50 mg 2x 100 mg ACR20 45% 56% 62% 69% 57% 59% 80% p-value vs placebo (multiplicity-corrected) < Primary endpoint achieved 16

17 % responders ACR responses at W12 ITT-NRI Placebo 50 mg 100 mg 200 mg 2x25 mg 2x50 mg 2x100 mg qd bid qd bid qd bid ACR20 ACR50 ACR70 : p<0.05; : p<0.01; : p<

18 % responders ACR responses at W12 ITT-LOCF Placebo 50 mg 100 mg 200 mg 2x25 mg 2x50 mg 2x100 mg qd bid qd bid qd bid ACR20 ACR50 ACR70 : p<0.05; : p<0.01; : p<

19 DAS28(CRP) ITT-LOCF Mean change from baseline 0.0 qd vs placebo 0.0 bid vs placebo Week Week Placebo 50 mg 100 mg 200 mg Placebo 2x25 mg 2x50 mg 2x100 mg : p<0.05; : p<0.01; : p<

20 DAS28(CRP) at W12 ITT-LOCF: remission rate & low disease activity % responders 100 Remission (%) Low disease activity (%) Placebo 50 mg 100 mg 200 mg 2x25 mg 2x50 mg 2x100 mg 20

21 Subject Global Assessment VAS ITT-LOCF Mean change from baseline 0.0 qd vs placebo 0.0 bid vs placebo Week Week Placebo 50 mg 100 mg 200 mg Placebo 2x25 mg 2x50 mg 2x100 mg : p<0.05; : p<0.01; : p<

22 Overview of adverse events (AE) 50 mg/day 100 mg/day 200 mg/day Placebo qd bid qd bid qd bid Total Treatment-emergent AE 37% 41% 37% 31% 42% 44% 43% 39% Serious treatmentemergent AE 2% 0% 1% 4% 0% 0% 2% 1% Low incidence of treatment-emergent AEs and SAEs, no deaths Even distribution over dose groups, including placebo Few serious treatment-emergent infections (0.5% - blinded) 22

23 Hemoglobin & neutrophils Changes from baseline at W mg/day 100 mg/day 200 mg/day Placebo qd bid qd bid qd bid Hemoglobin (g/l) Neutrophils (giga/l) No discontinuations due to anemia or neutropenia Hemoglobin increases Normalization of neutrophils 23

24 ALT Within first 12 weeks of treatment 50 mg/day 100 mg/day 200 mg/day Placebo qd bid qd bid qd bid Total grade 1: ]1.0,2.5] x ULN 4 (5%) 4 (5%) 6 (7%) 7 (8%) 6 (7%) 7 (8%) 4 (5%) 38 (6%) grade 2: ]2.5,5.0] x ULN blinded blinded blinded blinded blinded blinded blinded 4 (1%) grade 3-4: > 5.0 x ULN Worst case TE CTCAE grades Low incidence of grade 2, no grade

25 LDL vs HDL at W12 % change from baseline placebo 50 mg 100 mg 200 mg 2x25 mg 2x50 mg 2x100 mg -10 LDL HDL 25

26 Lipids Percent change from baseline at W12 #REF! 50 mg/day 100 mg/day 200 mg/day Placebo qd bid qd bid qd bid LDL -1.0% 5.8% 5.6% 5.7% 2.3% 8.0% 11.9% HDL -0.1% 6.5% 5.7% 8.5% 9.3% 21.2% 23.1% Total cholesterol/hdl -0.3% 1.5% 1.5% -0.5% -0.9% -6.9% -4.8% HDL increases with dose Improved total cholesterol/hdl ratio (atherogenic index) at 200mg/day 26

27 Conclusions Primary endpoint achieved All key efficacy endpoints achieved High ACR50 & ACR70 responses Fast onset within one week Safety profile is consistent with previous filgotinib RA studies Confirms rationale for JAK1 27

28 Thank you Patients Investigators Team AbbVie 28

29 DARWIN in upcoming months Add-on to MTX 594 patients Monotherapy 287 patients Long term extension 24 week data July 12 week data beginning of May 24 week data August 98% rollover rate from DARWIN 1&2 29

30 Filgotinib: multiple Phase 2 readouts CF program on track to deliver combination therapy Fully owned programs in IBD/IPF Proprietary target discovery to feed pipeline Strong balance sheet to support R&D 30