¾ Primary efficacy analysis (mITT population) included 194 subjects: 400 mg QD (48), 800 mg QD (53), 400 mg BID (46), and placebo (47). ¾ Least squares mean percent change from baseline was statistically significant compared with placebo for the 800 mg QD group (-48.2% vs -25.0%; P=.001) and the 400 mg BID group (-50.7% vs -25.0%; P<.001); the difference between 400 mg QD and placebo did not reach statistical significance (-38.1% vs -25.0%; P=.066) (Table 1) (Figure 1). ¾ Diarrhea was the most common TEAE, reported in 22.4%, 40.0%, 39.6%, and 14.6% of subjects in the XP-23829 400 mg QD, 800 mg QD, 400 mg BID, and placebo groups, respectively. Most cases of diarrhea were mild to moderate in severity (Table 2). ¾ Nausea and abdominal pain were reported in more than 10% of the overall XP-23829 population (Table 2). ¾ Flushing was reported in 5.9% of XP-23829 subjects and 6.3% of placebo subjects (Table 2). ¾ No subject demonstrated grade 3 or 4 lymphopenia (Table 2). ¾ No new or unexpected adverse events related to XP-23829 were reported compared to what is known for the FAE class (Table 2). XP-23829, a novel fumaric acid ester, is efficacious in reducing psoriatic lesions: Results from a phase 2 randomized controlled study Alice B. Gottlieb, MD, PhD1; Caitriona Ryan, MD2; Richard Kim, MD3; Aftab Alam, MBBS, MS, MBA4; Sagar Munjal, MD, MS4; Leon Kircik, MD5 1New York Medical College, Valhalla, NY; 2St. Vincent’s University Hospital, Dublin, Ireland; 3RKK Consulting, Inc, Redwood City, CA; 4Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories, Princeton, NJ; 5DermResearch, PLLC, Louisville, KY Conclusions ¾ In this study XP-23829 in 400 mg BID and 800 mg QD doses demonstrated significant efficacy over 12-week of treatment and efficacy did not appear to have plateaued at the end of the study. ¾ Efficacy and safety is being further assessed in a 24-week phase 2 study. Methods Table 1. Least Squares Mean for Percentage Change in Total PASI Score ¾ Randomized, double-blind, placebo-controlled, dose-finding efficacy and safety study in 33 US sites. ¾ Patients with chronic plaque psoriasis > 6 months, PASI (Psoriasis Area and Severity Index) ≥ 12, sPGA (static Physician Global assessment) ≥ 3, and psoriasis BSA (Body Surface Area) ≥ 10%. ¾ 200 subjects randomized in a 1:1:1:1 ratio into 4 arms: 400 mg QD, 400 mg BID, 800 mg QD, Placebo. ¾ A 3-week titration phase was followed by 9 weeks of treatment. ¾ The primary endpoint was the percentage change in PASI score from baseline to the end of week 12. Financial Support: This study was supported by the Dr Reddy’s Laboratories group of companies and by Xenoport, Inc. now Arbor Pharmaceuticals, LLC. DRL Publication #816 Results Introduction ¾ Dimethyl Fumarate (DMF) is a fumaric acid ester (FAE) approved in Germany for the treatment of moderate to severe chronic plaque psoriasis. Monomethyl fumarate (MMF) is the active moiety of DMF. ¾ XP-23839 is an extended release FAE that is being developed for the treatment of moderate to severe plaque psoriasis. ¾ Here, we examine a phase 2 study to evaluate the safety and efficacy of 3 doses and 2 dosing regimens at 12 weeks. Table 2. Frequent Treatment-Emergent Adverse Effects (≥10%) XP-23829 400 mg QD (N=48) XP-23829 800 mg QD (N=53) XP-23829 400 mg BID (N=46) Placebo (N=47) Overall mITT Population LSM (SE) P Value vs Placebo LSM (SE) P Value vs Placebo LSM (SE) P Value vs Placebo LSM (SE) Week 12 -38.1 (5.07) 0.066 -48.2 (5.06) .001 -50.7 (5.50) < .001 -25.0 (5.06) XP-23829 400 mg QD (N=49) XP-23829 800 mg QD (N=55) XP-23829 400 mg BID (N=48) XP-23829 (N=152) Placebo (N=48) Any TEAE 36 (73.5) 42 (76.4) 37 (77.1) 115 (75.7) 29 (60.4) Diarrhea 11 (22.4) 22 (40.0) 19 (39.6) 52 (34.2) 7 (14.6) Nausea 6 (12.2) 4 (7.3) 10 (20.8) 20 (13.2) 6 (12.5) Abdominal pain 1 (2.0) 7 (12.5) 11 (22.9) 19 (12.5) 2 (4.2) Flushing 4 (8.2) 3 (5.5) 2 (4.2) 9 (5.9) 3 (6.3) Headache 2 (4.1) 3 (5.5) 5 (10.4) 10 (6.6) 2 (4.2) Vomiting 3 (6.1) 7 (12.7) 1 (2.1) 11 (7.2) 1 (2.1) LSM = least squares mean; SE = standard error Figure 1. Least Squares Mean % Change From Baseline in PASI Score Over Time PPN-06 vs Fumaderm Table 3. Maximum Lymphocyte Grades at Any Given Visit 400 mg QD (N=49) 800 mg QD (N=55) 400 mg BID (N=48) Placebo (N=48) Grade 1 3 (6.1%) 5 (9.1%) 7 (14.6%) 2 (4.2%) Grade 2 2 (4.1%) 2 (3.6%) 1 (2.1%) 0 Grade 3 or 4 0 0 0 0 -60 -50 -40 -30 -20 -10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 P er ce nt C ha ng e Week PPN-06 Phase 2 Placebo PPN-06 400 mg QD PPN-06 800 mg QD PPN-06 400 mg BID -25.0 -38.1 -48.2 -50.7 Titration Steady-State Dosing FC17PosterPromiusGottliebXP23829.pdf