Scott D. Beattie

Natural History of Cardiovascular Disease in Patients With Diabetes: Role of hyperglycemia

Atherosclerotic vascular disease is more common in diabetic than in nondiabetic individuals. Diabetic macrovascular disease also has a more severe course with greater prevalence of multiple-vessel coronary artery disease and more diffuse elongated atheromas in affected blood vessels. In this review, we discuss possible reasons for increased incidence of cardiovascular (CV) events in individuals with diabetes. Although an increased prevalence of standard CV risk factors has been clearly documented in association with diabetes, diabetes-related abnormalities, particularly hyperglycemia, also play an important role. Epidemiological studies suggest that the effect of hyperglycemia on CV risk is independent of other known risk factors, but no data from primary interventional trials are available yet. Analysis of datasets from populations that included individuals with impaired glucose tolerance and impaired fasting glucose suggest that the pathogenic role of hyperglycemia on the blood vessel wall already exists in the early stages of glucose intolerance. The effect of postprandial or postchallenge hyperglycemia seems to be greater than the effect of fasting blood glucose abnormalities. The relationship of postprandial glycemia, fasting blood glucose, and CV risk in individuals with diagnosed (or overt) diabetes is less clear, although most reports indicate a greater pathogenic potential of postprandial hyperglycemia rather than fasting hyperglycemia. Based on the results of epidemiological reports, the most appropriate targets in interventional trials are postprandial hyperglycemia or A1C.

Baricitinib in Patients with Refractory Rheumatoid Arthritis

BACKGROUND In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2 inhibitor, reduced disease activity in patients with rheumatoid arthritis who had not previously received treatment with biologic disease-modifying antirheumatic drugs (DMARDs). METHODS In this phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to control type 1 error, were the American College of Rheumatology 20% (ACR20) response (primary end point), the Health Assessment Questionnaire-Disability Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score of 3.3 or less (on a scale of 0.1 to 86.0, with a score of 3.3 or less indicating remission). Comparisons with placebo were made first with the 4-mg dose of baricitinib and then with the 2-mg dose. RESULTS Significantly more patients receiving baricitinib at the 4-mg dose than those receiving placebo had an ACR20 response at week 12 (55% vs. 27%, P<0.001). Differences between the higher-dose baricitinib group and the placebo group were also significant for the HAQ-DI score and the DAS28-CRP but not for an SDAI score of 3.3 or less. Adverse-event rates through 24 weeks were higher for patients receiving the 2-mg dose of baricitinib and those receiving the 4-mg dose than for patients receiving placebo (71% and 77%, respectively, vs. 64%), including infections (44% and 40%, vs. 31%). The rates of serious adverse events were 4%, 10%, and 7% in the three groups, respectively. Two nonmelanoma skin cancers and two major adverse cardiovascular events, including a fatal stroke, occurred in the higher-dose group. Baricitinib was associated with a small reduction in neutrophil levels and increases in serum creatinine and low-density lipoprotein cholesterol levels. CONCLUSIONS In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01721044.).

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate.

Objectives To investigate baricitinib (LY3009104, formerly INCB028050), a novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate. Methods In this phase IIb study, 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for an additional 12 weeks. Patients assigned to placebo or 1 mg baricitinib were reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 12–24. The primary endpoint was the proportion of patients in the combined 4 and 8 mg groups achieving an American College of Rheumatology 20% (ACR20) response versus placebo at week 12. Results Significantly more patients in the combined baricitinib 4 and 8 mg groups compared with placebo achieved an ACR20 response at week 12 (76% vs 41%, p<0.001). At week 12, significant differences versus placebo were also observed in patients achieving ACR50, ACR70 and remission as measured by Disease Activity Score for 28-joint counts, Clinical Disease Activity Index and Simplified Disease Activity Index. Patients receiving 2, 4, or 8 mg baricitinib maintained or improved in all measures through 24 weeks. Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups. Serious infections developed in three patients receiving baricitinib. No cases of tuberculosis, herpes zoster, opportunistic infections or deaths were reported. Dose-dependent decreases in haemoglobin were observed with baricitinib. Conclusions Baricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease. Baricitinib was well tolerated with no unexpected safety findings through week 24. Trial registration number NCT01185353.

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage. Trial registration number NCT01721057; Results.

Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease‐Modifying Antirheumatic Drug Treatment

We undertook this phase III study to evaluate baricitinib, an orally administered JAK‐1/JAK‐2 inhibitor, as monotherapy or combined with methotrexate (MTX) compared to MTX monotherapy in patients with active rheumatoid arthritis (RA) who had received no or minimal conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) and who were naive to biologic DMARDs.

LB0005 12-week results of a phase 2B dose-ranging study of LY3009104 (INCB028050), an oral JAK1/JAK2 inhibitor, in combination with traditional dmards in patients with rheumatoid arthritis

Background LY3009104 (LY) is a novel, oral inhibitor of the JAK1/JAK2 signalling pathway known to be important in the pathobiology of rheumatoid arthritis (RA). Objectives To compare efficacy and safety of LY versus placebo (PBO) in patients (pts) with moderate to severe RA with inadequate response to methotrexate (MTX). Methods In this Phase 2b, 24-week randomized, double-blind, PBO-controlled study, pts with active RA on stable MTX were randomized 2:1:1:1:1 to receive either PBO or 1 of 4 once-daily LY doses (1, 2, 4, or 8 mg) for 12 weeks. The primary endpoint to evaluate the efficacy of LY was assessed by the combined proportion of pts in the 4-mg and 8-mg dose groups who achieved an ACR20 response compared to PBO over 12 weeks. Results Of the 301 pts randomized and treated, 76% of the combined 4- and 8-mg (75% of the 4-mg and 78% of the 8-mg dose) groups achieved ACR20 responses compared with 41% of PBO-treated pts (p ≤.001) by the end of 12 weeks. Similarly, greater proportions of pts achieved disease remission as judged by DAS28-CRP in the 4-mg (37%) and 8-mg (22%) dose groups compared to PBO (4%; Table 1). Onset of efficacy was rapid for ACR20, ACR50, ACR70, and DAS28-CRP, with statistically significant differences seen from Week 2 onwards. A greater percentage of pts achieved the MCID for the HAQ-DI in the 4-mg (60%) and 8-mg (67%) dose groups compared to PBO (41%) at week 12. Most adverse events (AEs) were mild. A similar rate of infections was observed in PBO (12%) and combined LY (14%) groups representing the most common treatment emergent AE. No deaths or opportunistic infections occurred in the active treatment groups. One pt taking PBO was diagnosed with an opportunistic infection of toxocariasis. Serious AEs were reported in 6 pts (2 in PBO; 3 in 2-mg; 1 in 8-mg). Decreases in hemoglobin, small increases in serum creatinine, and increases in LDL and HDL were seen (Table 2). Pt demographics across treatment groups were similar (83% female, mean age 51 years, mean duration of RA 5–7 years, HAQ-DI, 1.02–1.31; DAS28 [ESR], 6.0–6.6). Table 1. Endpoints PBO 1 mg LY 2 mg LY 4 mg LY 8 mg LY 4+8 mg LY (N=98) (N=49) (N=52) (N=52) (N=50) (N=102) % ACR20† 41 57* 54 75** 78** 76** % ACR50† 10 31* 17 35** 40** 37** % ACR70† 2 12* 8 23** 20** 22** DAS28-CRP†§ –1.0 –1.5* –1.4* –2.2** –2.1** N/A % DAS28 <2.6† 4 14* 15* 37** 22** N/A †Non-responder imputation and 1-sided p-value (Fisher’s exact test); §2-sided p-value from LY dose vs PBO (ANCOVA: treatment is a fixed factor and baseline is a covariate [LS mean change, LOCF]); *p<0.05; **p≤0.001 vs. PBO. Table 2. Mean (SD) Change from Baseline; 12 Weeks PBO 4 mg LY 8 mg LY Hemoglobin (g/dL) –0.14 (0.62) –0.15 (0.80) –0.57 (0.92) Neutrophil count (103/mm3) –0.03 (1.52) –0.30 (1.79) –0.68 (2.06) Creatinine (mg/dL) 0.01 (0.08) 0.11 (0.36) 0.09 (0.27) HDL cholesterol (mg/dL) 0.92 (11.57) 7.55 (13.40) 7.25 (13.92) LDL cholesterol (mg/dL) –4.4 (25.06) 9.5 (30.29) 12.0 (23.36) Conclusions Clinical efficacy of LY against PBO was demonstrated in this Phase 2b study of LY in combination with background MTX in pts with moderate to severe RA. LY was well tolerated. No new safety signals were detected when compared to previously conducted studies with LY. Disclosure of Interest E. Keystone Grant/Research support from: Abbott Laboratories, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Centocor Inc, F.Hoffman-La Roche Inc, Genzyme Inc, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, Consultant for: Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Centocor Inc, F.Hoffman-La Roche Inc, Genentech Inc, Merck, Nycomed, Pfizer Pharmaceuticals, UCB, Speakers Bureau: Abbott Laboratories, Bristol-Myers Squibb Company, F.Hoffman-La Roche Inc, Merck, Pfizer Pharmaceuticals Inc, UCB, Amgen, Janssen Inc., P. Taylor Grant/Research support from: AstraZeneca, Merck, UCB, Celgene, Consultant for: Eli Lilly & Co, Celgene, UCB, Novartis, Merck, NovoNordisk, Abbott, Pfizer, AstraZeneca, Roche, Takeda, M. Genovese Grant/Research support from: Lilly, Pfizer, Rigel, AstraZeneca, Consultant for: Lilly, Pfizer, Rigel, AstraZeneca, Vertex, Biogen-Idec, Astellas, D. Schlichting Shareholder of: Eli Lilly & Co, Employee of: Eli Lilly & Co, S. Beattie Shareholder of: Eli Lilly & Co, Employee of: Eli Lilly & Co, C. Gaich Shareholder of: Eli Lilly & Co, Employee of: Eli Lilly & Co, R. Fidelus Gort Employee of: Incyte Corp., M. Luchi Shareholder of: Incyte Corp., Employee of: Incyte Corp., W. Macias Shareholder of: Eli Lilly & Co, Employee of: Eli Lilly & Co

OP0029 Baricitinib, An Oral Janus Kinase (JAK)1/JAK2 Inhibitor, in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to TNF Inhibitors: Results of the Phase 3 RA-Beacon Study

Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naïve to biologic DMARDs (bDMARDs).1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Wk 12 Wk 24 PBO 2 mg QD 4 mg QD PBO 2 mg QD 4 mg QD (N=176) (N=174) (N=177) (N=176) (N=174) (N=177) ACR20 27 49*** 55*** 27 45*** 46*** ACR50 8 20** 28*** 13 23* 29*** ACR70 2 13*** 11** 3 13*** 17*** DAS28-hsCRP ≤3.2 9 24*** 32*** 11 20* 33*** DAS28-hsCRP <2.6 4 11** 16*** 6 11 22*** DAS28-ESR ≤3.2 4 13** 12** 7 12 17** DAS28-ESR <2.6 1 6** 6* 3 5 9* CDAI ≤10 11 24** 28*** 15 23 31*** CDAI ≤2.8 2 3 6 3 5 9* SDAI ≤11 9 22*** 28*** 14 22* 31*** SDAI ≤3.3 2 2 5 2 5 9** HAQ-DI MCID ≥0.22 43 59** 67*** 30 50*** 53*** Data are % patients achieving response (NRI);* p≤0.05,** p≤0.01,*** p≤0.001 vs. PBO. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB

A1.72 Baricitinib, an oral janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in an open-label, long-term extension study1

Background Baricitinib (formerly LY3009104/INCB028050) is a novel, oral inhibitor of JAK1 and JAK2 in the JAK-STAT signalling pathway being investigated as a treatment for rheumatoid arthritis (RA). Objectives To report 52 week safety and efficacy findings of an open label extension of the phase 2b study. Methods Patients (Pts) were initially randomised to placebo (PBO) or 1of 4 once-daily (QD) baricitinib doses (1, 2, 4, or 8 mg) for 12 wks. Pts assigned to 2 mg, 4 mg or 8 mg continued assigned treatment and pts assigned to placebo or 1 mg were reassigned to 4 mg QD or 2 mg BID for an additional 12 weeks of blinded treatment. In the open label portion of the study, patients in 8 mg group continued to receive 8 mg QD and all other patients received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at the investigator’s discretion when >6 tender and swollen joints were present. Analyses reported here include data through 52 weeks for patients treated in the open-label extension (non-responder imputation used for discontinued patients). Results Of the 212 pts eligible to participate, 201(95%) pts entered the open label extension, 184 patients completed 52 weeks of treatment, 15 pts discontinued, and 2 pts had not yet completed 52 weeks. Among pts who remained on 4 mg (n = 108), TEAEs occurred in 57 (53%), SAEs in 14 (13%), infections in 34 (31%) and serious infections in 4 (4%). Among pts who received 8 mg at any time (n = 93), TEAEs occurred in 59 (63%), SAEs in 8 (9%), infections in 37 (40%) and serious infections in 2 (2%). No opportunistic infections or TB cases were observed. There was one death due to myocardial infarction in the 8 mg group. Among all patients combined in the open label extension, the proportions of pts achieving ACR20, ACR50, ACR70, CDAI Remission, SDAI Remission, DAS28CRP ≤3.2, DAS28CRP <2.6, DAS28ESR ≤3.2, DAS28CRP <2.6 or the ACR/EULAR Boolean remission at the start of the open label extension (week 24) were similar or increased at week 52 (Table). Conclusions Among pts completing 52 weeks of a phase 2b study, clinical improvements observed at week 24 were maintained or improved during the open label extension. Safety signals observed over the open label extension were consistent with previously reported results of baricitinib. Reference 1.1. EULAR 2013, Ann Rheum Dis 2013;72 Supplement 3:65, Genovese et al.

Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase IIb Study of Patients With Active Rheumatoid Arthritis

To assess the effects of baricitinib on lipid profiles in patients with moderate‐to‐severe rheumatoid arthritis.

FRI0124 Temporary interruptions of study drug during the baricitinib phase 3 rheumatoid arthritis program

Background Temporary interruption of RA therapy is common in clinical practice; therefore, rapid clearance and low immunogenicity may be useful DMARD attributes. Baricitinib (bari) is a non-biologic Janus kinase (JAK) 1 /JAK2 selective inhibitor with a pharmacokinetic half-life in RA patients of approximately 13 hours. It has demonstrated improved clinical efficacy compared to MTX, adalimumab and placebo (pbo) with a satisfactory safety profile when administered once daily to RA patients in 4 completed Phase 3 studies. Objectives These analyses aimed to characterize temporary interruptions of study drug during these studies and explore the kinetics of RA symptoms during and following interruption. Methods During bari Phase 3 studies, investigators were required to document temporary interruptions of study drug, including timing, reason and duration, using electronic case report forms. In 2 studies, patients recorded RA symptoms (duration and severity of morning joint stiffness, worst tiredness and worst joint pain) daily for 12 weeks. Post hoc analyses investigated changes in these scores among patients randomized at least 7 days prior to interruption, having an interruption that lasted at least 3 days, and retreated. Results Across the 3 pbo-controlled studies, interruptions occurred in a larger proportion of patients with bari than pbo only in the biologic DMARD-inadequate responder (IR) study RA-BEACON. In the 2 active comparator-controlled studies, the lowest rates of interruption were in the bari monotherapy arm of the DMARD-naïve MTX-controlled RA-BEGIN study, and proportions were similar for bari and adalimumab in the MTX-IR study, RA-BEAM (Table 1). Adverse events (predominantly non-serious, mild or moderate infections, most commonly of the respiratory tract) were the most frequent reason for interruption. Few patients interrupted for the reason of abnormal laboratory results. Most interruptions lasted for 2 weeks or less; in RA-BEAM, interruptions appeared shorter in duration for bari than for adalimumab. Diary measures indicated modest symptom increases during interruption compared to the last pre-interruption value, with a return to pre-interruption values or better after resumption of study drug (Table 2). Conclusions Consistent with its pharmacologic properties, brief temporary interruptions of bari during Phase 3 studies were associated with minor increases in RA symptoms, which resolved following resumption of therapy. A small molecule with a short half-life may offer advantages over injectable biologic therapies with respect to drug interruption for clinical cause in RA patients. Disclosure of Interest P. Emery Consultant for: Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, Eli Lilly and Company, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, janssen, Eli Lilly and Company, GlaxoSmithKline, T. Cardillo Employee of: Eli Lilly and Company, D. Schlichting Employee of: Eli Lilly and Company, S. Beattie Employee of: Eli Lilly and Company, L. Chen Employee of: Eli Lilly and Company, T. Rooney Employee of: Eli Lilly and Company, J. Smolen: None declared