A. Elegbe

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial

Objectives To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA). Methods AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX. Results Of 646 patients randomised, 79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2, efficacy outcomes, including radiographic, remained comparable between groups and with year 1 results. The American College Rheumatology 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%) including two cases of tuberculosis with adalimumab. There were fewer discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious infections (0/12 vs 9/19 patients) in the abatacept group. Injection site reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%). Conclusions Through 2 years of blinded treatment in this first head-to-head study between biologic disease-modifying antirheumatic drugs in RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept. ClinicalTrials.gov Identifier NCT00929864.

Immunogenicity, Safety, and Efficacy of Abatacept Administered Subcutaneously With or Without Background Methotrexate in Patients With Rheumatoid Arthritis: Results From a Phase III, International, Multicenter, Parallel‐Arm, Open‐Label Study

To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy.

Longterm Safety and Efficacy of Abatacept Through 5 Years of Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitor Therapy

Objective. To evaluate abatacept safety and efficacy over 5 years in patients with rheumatoid arthritis (RA) who had inadequate response to anti-tumor necrosis factor (TNF) therapy in the ATTAIN trial. Methods. Patients completing the 6-month, double-blind (DB) placebo-controlled period were eligible to enter the longterm extension (LTE), where all patients received abatacept every 4 weeks (∼10 mg/kg, according to weight range). Safety, efficacy, physical function, and health-related quality of life were monitored throughout. Results. In total, 317 patients (218 DB abatacept, 99 DB placebo) entered the LTE; 150 (47.3%) completed it. Overall incidences of serious adverse events, infections, serious infections, malignant neoplasms, and autoimmune events did not increase during the LTE versus the DB period. American College of Rheumatology responses with abatacept at Month 6 were maintained over 5 years. At Year 5, among patients who received abatacept for 5 years and had available data, 38/103 (36.9%) achieved low disease activity as defined by the 28-joint Disease Activity Score (DAS28)/C-reactive protein (CRP); 23/103 (22.3%) achieved DAS28/CRP-defined remission. Health Assessment Questionnaire response was achieved by 62.5% of patients remaining on treatment at Year 5; mean improvements from baseline in physical component summary and mental component summary scores were 7.34 and 6.42, respectively. High proportions of patients maintained efficacy and physical function benefits or improved their disease state at each timepoint throughout the LTE, if remaining on abatacept treatment. Conclusion. Safety remained consistent, and abatacept efficacy was maintained from 6 months to 5 years, demonstrating the benefits of switching to abatacept in this difficult-to-treat population of patients with RA previously failing anti-TNF therapy.

Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome

Introduction Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration−approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings. Methods In this report, we describe the rationale for and design of a randomized, placebo-controlled, clinical trial of abatacept in patients with treatment-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis or minimal change disease. The design is a hybrid of a parallel-group and crossover design (switchover) with the primary objectives assessed in the first period of the study and the secondary objectives assessed using data from both periods. All participants will receive the active agent in 1 of the periods. The duration of treatment will be 4 months per period. Results The primary outcome will be improvement in nephrotic-range proteinuria to subnephrotic range, that is, reduction from baseline to 4 months in urine protein:creatinine ratio ≥ 50% and to a level < 3. The projected sample size is 90 patients, which has 80% power to detect a treatment difference of 28%. Conclusion This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients.

FRI0193 SC vs IV abatacept in RA: post-hoc efficacy analysis of long-term acquire (SC) data with aim (IV) data

Background ACQUIRE was a Ph IIIb study demonstrating comparability of SC and IV abatacept (ABA) over a 6-mth DB period. At 6 mths, all patients (pts) entered an open-label (OL) period in which they received SC ABA. AIM was a Ph III 12-mth, DB, placebo-controlled study of IV ABA, also with an OL extension. Pts in both trials had moderate-to-severe RA, inadequate response to MTX and similar BL demographics and disease activity. Objectives To provide a long-term (LT) comparison of SC and IV ABA, we performed a post-hoc efficacy analysis of LT data from the OL periods of ACQUIRE and AIM. Methods In ACQUIRE, pts received 125 mg SC ABA weekly (after 10 mg/kg IV load on Day 1) +MTX. In AIM, pts received ∼10 mg/kg IV ABA every 4 weeks (after loading doses on Days 1, 15 & 29) +MTX; only pts who received ABA in DB and OL periods were included in this analysis. LT analysis began at Day 253 for ACQUIRE; Day 225 was selected as a comparison starting point for AIM. The most recent LT data lock for ACQUIRE (Day 897) was then used as the comparison end date for AIM as well. At the time of analysis, however, not all ACQUIRE pts had reached this later time point. As-observed data were used to assess both response to treatment (ACR 20, 50 and 70) and disease status (DAS28[CRP], SDAI and CDAI). No safety analyses were performed on this subset as larger pooled safety analyses are presented elsewhere. Results In the OL period of ACQUIRE, 1372 pts received SC ABA compared with 378 pts who received IV ABA in AIM. ACR 20, 50 and 70 rates, and DAS remission rates were sustained from Days 253/225 through Day 897 for ACQUIRE/AIM, respectively (Table). SDAI and CDAI remission rates at Day 253 (13.3%; 179/1341 and 15.6%; 211/1349) were maintained up to Day 897 (20.2%; 123/608 and 22.1%; 143/646) in ACQUIRE; in AIM, corresponding rates at Day 225 (9.9%; 36/365 and 12.2%; 45/369) were similarly maintained up to Day 897 (15.0%; 45/300 and 16.7%; 52/311). Table 1 Efficacy Parameter Study Day ACQUIRE SC ABA AIM IV ABA ACR 20  Subjects, n/m (%) Start of Comparison 968/1080 (89.6) 250/269 (92.9)  (95% CI) (87.8, 91.4) (89.9, 96.0)  Subjects, n/m (%) Day 897 493/544 (90.6) 215/236 (91.1)  (95% CI) (88.2, 93.1) (87.5, 94.7) ACR 50  Subjects, n/m (%) Start of Comparison 563/719 (78.3) 134/161 (83.2)  (95% CI) (75.3, 81.3) (77.5, 89.0)  Subjects, n/m (%) Day 897 285/371 (76.8) 107/145 (73.8)  (95% CI) (72.5, 81.1) (66.6, 81.0) ACR 70  Subjects, n/m (%) Start of Comparison 284/369 (77.0) 58/81 (71.6)  (95% CI) (72.7, 81.3) (61.8, 81.4)  Subjects, n/m (%) Day 897 130/196 (66.3) 45/72 (62.5)  (95% CI) (59.7, 72.9) (51.3, 73.7) DAS Remission  Subjects, n/m (%) Start of Comparison 210/331 (63.4) 37/61 (60.7)  (95% CI) (58.3, 68.6) (48.4, 72.9)  Subjects, n/m (%) Day 897 104/166 (62.7) 37/54 (68.5)  (95% CI) (55.3, 70.0) (56.1, 80.9) Conclusions SC abatacept provided similar efficacy to IV abatacept when compared across these 2 trials; overall, efficacy achieved in the short term was maintained in the LT. Disclosure of Interest M. Genovese Consultant for: Bristol-Myers Squibb, C. Pacheco Tena: None Declared, A. Covarrubias Cobos Grant/Research support from: Bristol-Myers Squibb, G. Leon: None Declared, E. Mysler Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, M. Keiserman Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, R. Valente Grant/Research support from: Pfizer, UCB, BMS, Roche, Takeda, and Lilly, P. Nash Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, J. Simon Campos Speakers Bureau: Bristol-Myers Squibb, J. Box Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, C. Legerton III: None Declared, E. Nasonov Speakers Bureau: Roche; Bristol-Myers Squibb Company; Abbott Laboratories; Merck Sharp & Dohme Corp; UCB Pharma, Inc, P. Durez Speakers Bureau: Bristol-Myers Squibb, I. Delaet Employee of: Bristol-Myers Squibb, A. Elegbe Employee of: Bristol-Myers Squibb, R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

Objective. To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). Methods. The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Results. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. Conclusion. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

OP0253 A phase iii randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of abatacept or placebo on standard of care in patients with active class iii or iv lupus nephritis

Background The tenets of novel treatment strategies for active class III or IV lupus nephritis (LN) aim to improve renal response rates as well as the speed, robustness and durability of responses; decrease extra-renal SLE disease activity; reduce glucocorticoid exposure; ensure tolerability and provide acceptable treatment-related safety profile. Objectives Compare efficacy and safety of IV abatacept (ABA), a selective T cell co-stimulation modulator, vs placebo (pbo), on background therapy for active proliferative LN. Methods This was a 24-mth, randomised, Phase III, multicentre, double-blind study with an open-ended, blinded long-term extension. Patients (pts) were randomised to pbo or ABA IV 30 mg/kg for 3 mths, followed by ABA~10 mg/kg every 4 wks on a background of mycophenolate and glucocorticoids. The primary endpoint, complete response (CR) at 1 year, was a composite measure that required maintenance of glomerular filtration rate, urine protein-to-creatinine ratio (UPCR) ≤0.5, absence of urinary cellular casts and prednisone ≤10 mg/day. We report Yr 1 data and available post-Yr 1 data for all pts, all double-blind. Results 405 pts were randomised (ABA n=202; pbo n=203). At baseline, mean age was 33 years, mean UPCR=3.78, mean serum creatinine=0.93 mg/dL and mean GFR=95 mL/min. Yr 1 study completion rates were ABA 77%, pbo 79%; fewer ABA pts discontinued during Yr 2 (ABA 14%, pbo 22%) and beyond. There were no significant differences between treatment arms in the proportion of pts with CR after 52 wks of treatment (ABA 35.1%, pbo 33.5%, p=0.73; primary endpoint). Achievement of sustained CR (2 successive visits) occurred earlier and more frequently in ABA-treated pts (figure 1). These benefits were driven by improvement in proteinuria which was seen as early as Day 85 (adjusted mean change in UPCR ABA –2.50, pbo –2.00; adjusted difference from pbo [95% CI] –0.50 [–0.84,–0.16]) and was sustained beyond Yr 2 (Yr 2: ABA –3.13, pbo –2.72; adjusted difference from pbo [95% CI] –0.41 [–0.79,–0.03]). There was no negative impact of ABA on renal function (eGFR). Few non-renal adjudicated BILAG A or B events occurred in Yr 1 (ABA=13 [BILAG A=0], pbo=12 [BILAG A=2]). Safety in Yr 1 was consistent with the known profile of ABA (serious adverse event [SAE] rate ABA 24%, pbo 19%). SAE rates after Yr 1 improved (ABA 6%, pbo 13%). The death rate was similar at Yr 2 (ABA 7, pbo 6). Improvements in SLE-related pharmacodynamic markers (C3, C4 and anti-dsDNA autoAb) were more sustained in ABA-treated pts.Abstract OP0253 – Figure 1 Kaplan-meier plot of time to first sustained complete renal response during year 1 of double-blind period: all randomised and treated patients Conclusions The study failed to meet its primary endpoint of higher CR rate in pts with active class III or IV LN after 1 year of abatacept treatment. Abatacept-treated pts had more rapid improvement in proteinuria, which led to earlier, sustained CR. There was a favourable safety profile extending beyond 2 years of treatment. Disclosure of Interest R. Furie Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, M. Dooley Consultant for: Bristol-Myers Squibb, D. Wofsy Consultant for: GlaxoSmithKline, Novartis, Celgene, UCB, Sanofi, T. Takeuchi Grant/research support from: Bristol-Myers Squibb, Chugai Pharmaceutical Co, Daiichi Sankyo, Takeda, Teijin Pharma, AbbVie, Asahikasei Pharma, Mitsubishi Tanabe Pharma Co., Pfizer,and Taisho Toyama Pharmaceutical Co., Eisai, AYUMI Pharmaceutical Corporation, Nipponkayaku, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe Pharma Co., Abbivie, Nipponkayaku, Janssen, Astellas Pharma,Taiho Pharmaceutical, Speakers bureau: AbbVie,Bristol-Myers Squibb, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma Co., Pfizer, and Astellas Pharma, and Diaichi Sankyo, A. Malvar: None declared, A. Doria Consultant for: GSK, Pfizer, Eli Lily, Bristol-Myers Squibb, Speakers bureau: GSK, Pfizer, Eli Lily, Bristol-Myers Squibb, J. Romero-Díaz: None declared, T. Chan Grant/research support from: Astellas, Consultant for: Astellas, Novartis, Boehringer Ingelheim, Aurinia, A. Elegbe Employee of: Bristol-Myers Squibb, G. Appel Grant/research support from: Bristol-Myers Squibb, D. Jayne Grant/research support from: GSK, Roche, Sanofi, Consultant for: Aurinia, Boehringer, Chemocentryx, CSL, GSK, Inflx, Medimmune, Takeda, Sanofi, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

FRI0199 In patients with established RA, abatacept efficacy is independent of baseline annual radiographic progression rate

Background In the Phase III, double-blind, placebo (PBO)-controlled AIM study, abatacept (ABA)+ MTX significantly inhibited structural damage progression vs PBO+MTX in pts with established RA and inadequate response to MTX.1Sustained inhibition of radiographic progression was seen up to yr 5.2 Previous data in pts with early RA showed a benefit of ABA in pts with faster progression.3 Objectives To assess clinical outcomes at 1 yr according to annual radiographic progression rate (ARPR) by quartile at baseline (BL) in pts with established RA in AIM. Methods BL characteristics were similar between ABA 10 mg/kg+MTX (n=433) and PBO+MTX (n=219). ARPR was defined as total Genant-modified Sharpscore divided by disease duration. Pts were categorized into four quartiles according to ARPR at BL (Q1: ≤2.78; Q2: 2.78 to ≤4.64; Q3: 4.64 to ≤8.04; Q4: >8.04). For each quartile, treatment benefit was assessed post hoc by outcomes: DAS28(CRP)-derived criteria (remission <2.6; LDAS ≤3.2), Simplified Disease Activity Index Low Disease Activity (SDAI ≤11) and ACR50 response. Results Mean (SD) BL ARPR was 8.13 (18.11) for ABA+MTX and 5.87 (5.36) for PBO+MTX. For ABA+MTX vs PBO+MTX, the percentage of pts achieving an outcome at yr 1 by ARPR quartile is shown, with treatment differences (table). 95% CI of ABA vs PBO estimate of treatment difference did not cross zero for most ARPR quartiles. For LDAS (assessed by DAS28[CRP] or SDAI) and ACR50, there was a numerically higher treatment difference for pts in some of the higher quartiles (Q3/Q4). Table 1 % (95% CI) ARPR Q1 Q2 Q3 Q4 ABA+MTX (n=84) ABA+MTX (n=90) ABA+MTX (n=94) ABA+MTX (n=103) MTX (n=43) MTX (n=41) MTX (n=39) MTX (n=32) DAS28 LDAS ABA+MTX 42.9 (32.3, 53.4) 38.9 (28.8, 49.0) 45.7 (35.7, 55.8) 40.8 (31.3, 50.3) MTX 14.0 (3.6, 24.3) 19.5 (7.4, 31.6) 2.6 (0, 7.5) 6.3 (0, 14.6) Tx Δ 28.9 (9.9, 48.0) 19.4 (0.3, 38.5) 43.2 (23.8, 62.6) 34.5 (13.9, 55.2) <2.6 ABA+MTX 29.8 (20.0, 39.5) 18.9 (10.8, 27.0) 23.4 (14.8, 32.0) 26.2 (17.7, 34.7) MTX 2.3 (0, 6.8) 4.9 (0, 11.5) 0 (0, 0) 3.1 (0, 9.2) Tx Δ 27.4 (10.8, 44.0) 14.0 (-0.8, 28.8) 23.4 (7.7, 39.1) 23.1 (5.0, 41.2) SDAI LDAS ABA+MTX 52.4 (41.7, 63.1) 43.3 (33.1, 53.6) 44.7 (34.6, 54.7) 44.7 (35.1, 54.3) MTX 20.9 (8.8, 33.1) 24.4 (11.2, 37.5) 7.7 (0, 16.1) 6.3 (0, 14.6) Tx Δ 31.5 (11.6, 51.3) 18.9 (-0.7, 38.6) 37.0 (17.5, 56.5) 38.4 (17.4, 59.4) ACR50 ABA+MTX 61.4a (51.0, 71.9) 50.6b (40.2, 60.9) 54.3 (44.2, 64.3) 48.5 (38.9, 58.2) MTX 31.0c (17.0, 44.9) 22.0 (9.3, 34.6) 25.6 (11.9, 39.3) 12.5 (1.0, 24.0) Tx Δ 30.5 (10.1, 50.8) 28.6 (8.6, 48.6) 28.6 (8.2, 49.0) 36.0 (14.6, 57.5) Values are proportion of pts (%), except Tx Δ = treatment difference. an=83; bn=89; cn=42. Conclusions Over 1 yr, pts with established RA achieved better outcomes with abatacept +MTX than PBO+MTX across all quartiles. Pts with rapid radiographic progression (Q4) showed numerically greater clinical benefits in LDAS, SDAI and ACR50 compared with Q1 pts, extending previous findings in early RA.3 References Kremer J et al. Ann Intern Med 2006;144:865–76. Schiff M. Rheum 2011;50:437–49. Westhovens R et al. Ann Rheum Dis2011;70(Suppl 3):617. Disclosure of Interest P. Emery Grant/Research support from: Abbott Immunology Pharmaceuticals, Abbott Laboratories, BMS, Centocor Research and Development, Inc., Merck Pharmaceuticals, Pfizer Inc, Roche, UCB, Inc., Consultant for: Abbott Laboratories, Amgen Inc., BMS, Centocor Research and Development, Inc., Lilly USA, LLC., Merck Pharmaceuticals, Pfizer Inc, Roche, Schering-Plough, Takeda Pharmaceuticals North America, Wyeth Pharmaceuticals, UCB, Inc., Speakers Bureau: Abbott Immunology Pharmaceuticals, BMS, Centocor Research and Development, Inc., Merck Pharmaceuticals, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, UCB, Inc., R. Westhovens Grant/Research support from: Roche, UCB, Consultant for: Bristol-Myers Squibb, Centocor, Roche, Schering-Plough, Speakers Bureau: Bristol-Myers Squibb, M. Dougados Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, C. Gaillez Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Poncet: None Declared, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Elegbe Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, H. Genant Shareholder of: Synarc, Inc., Grant/Research support from: Bristol-Myers Squibb, GSK, Roche, Genentech, Pfizer, Consultant for: Bristol-Myers Squibb, GSK, Roche, Genentech, Amgen, Merck, Servier, Pfizer, Lilly, Employee of: Synarc, Inc.