OBJECTIVES Netakimab (NTK) is a humanised monoclonal antibody targeting interleukin-17A, previously investigated in a phase 1 trial in healthy volunteers. Here, we report the results of a phase 2 trial, conducted to assess safety and pharmacokinetics (PK), to establish a therapeutic dose of NTK in a target population of patients with active ankylosing spondylitis (AS). METHODS 89 patients with active AS, despite non-steroidal anti-inflammatory (NSAID) drug treatment, were randomised to receive 40, 80 or 120 mg of subcutaneous NTK or placebo at weeks 0, 1, 2 and q2wk thereafter until week 12. The primary endpoint was to achieve a proportion of patients with ≥20% improvement in Assessment of Spondyloarthritis. RESULTS Rates of ASAS20 response at week 16 for NTK with 95%CI for difference in ASAS20 rates NTK vs. placebo were 72.73% [1.69%;58.05%], 81.82% [12.36%;65.56%], 90.91% [23.71%;72.39%] at doses of 40, 80 and 120 mg. The response rate in the placebo arm was 42.86%. The pre-specified margin of clinically non-meaningful difference was 10%. Superiority to placebo was confirmed for doses 80 and 120 mg. The most frequent adverse events (AEs) were lymphocytosis, neutropenia, and asymptomatic bacteriuria. No dose-dependent toxicity or serious adverse events (SAEs) were observed. The most effective dose with the fastest response onset and favourable safety profile was 120 mg. CONCLUSIONS The data obtained demonstrate the efficacy and favourable safety profile of NTK in active AS. Clinical development of NTK will be continued in a phase 3 trial aimed to evaluate the efficacy of 1-year treatment with NTK 120 mg in patients with AS.

Background BCD-085 is an innovative humanised monoclonal antibody against interleukin-17 with genetically modified Fc- and CDR-regions, aimed to improve treatment outcomes in patients with several autoimmune disorders. Objectives This abstract presents the results of double-blind placebo controlled dose-finding phase II clinical study of efficacy and safety of subcutaneous BCD-085 in patients with ankylosing spondylitis. Methods The study was conducted as international multicenter randomised double-blind placebo controlled study. The study enrolled 88 adults with active AS. Patients were randomised in 4 study arms in 1:1:1:1 ratio to receive 40, 80 or 120 mg of BCD-085 or placebo. In the active period of the study, patients received the test drug/placebo SC injections once weekly for the first three weeks of treatment and then every other week till Wk 12. After Wk 12 all patients underwent follow-up for 4 weeks. Results Efficacy: BCD-085 is superior to placebo in doses 80 and 120 mg. ASAS20 at wk 16 was reached by 81.82%, 90.91% and 42.86% of patients in BCD-085 80 mg, 120 mg and placebo arm respectively (p=0.008, 95% CI for difference in proportion [12.36%; 65.56%]; p=0.001, 95% CI: 23.71% to 72.39%], superiority margin 10%). Significant reduction of AS activity was revealed for all BCD-085 arms: by Wk 4 BASDAI and ASDAS-CRP scores decreased and maintained achieved levels till the end of the study. Other secondary endpoints (ASAS40, ASAS5/6, BASMI, BASFI, BASDAI, MASES, chest expansion, QoL, spinal pain) had the corresponding dynamics: by the time of second evaluation (Wk 1 for spinal pain, Wk 4 for other endpoints) significant improvement with no further negative changes was revealed. For all evaluated endpoints the most pronounced response was established for BCD-085 120 mg arm. In placebo arm no significant dynamics was shown. Safety: All arms had highly similar safety profiles. Most of AEs were presented as mild or moderate laboratory abnormalities (ANC decreased, WBC increased) and moderate arterial hypertension. The rates of AEs were equivalent for all BCD-085 doses and placebo. There were no cases of SAEs, treatment discontinuation due to safety reasons or local reactions. Immunogenicity assessment did not detect formation of binding antibodies.Abstract OP0028 – Table 1 Summarised safety data Parameter Arm P-value BCD-08540 mg(n=22) BCD-08580 mg(n=22) BCD-085120 mg(n=22) Placebo(n=22) Any AE 11 (50.00%) 6 (27.27%) 4 (18.18%) 7 (31.82%) 0.183 Therapy-related AEs 5 (22.73%) 4 (18.18%) 1 (4.55%) 5 (22.73%) 0.354 Grade 3–4 AEs 1 (4.55%) 2 (9.09%) 0 1 (4.55%) 0.900Abstract OP0028 – Figure 1 ASAS20 response throughout the study (* – statistically significant difference between BCD-085 and placebo arms). Conclusions Treatment with BCD-085 leads to significant improvement in all AS symptoms in comparison with placebo. The dose of 120 mg of BCD-085 had the most pronounced effect. The drug was well tolerated in all doses with no differences with placebo in safety profiles. Disclosure of Interest V. Mazurov: None declared, S. Erdes: None declared, E. Kunder: None declared, N. Soroka: None declared, P. Shesternya: None declared, S. Smakotina: None declared, T. Raskina: None declared, D. Krechikova : None declared, T. Dubinina: None declared, A. Eremeeva Employee of: JSC BIOCAD, E. Dokukina Employee of: JSC BIOCAD, E. Chernyaeva Employee of: JSC BIOCAD, R. Ivanov Employee of: JSC BIOCAD

Background Equivalent efficacy of BCD-055 and infliximab (INF) innovator has been previously established (the primary endpoint: ACR20 at Wk14)1. Objectives The impact of BCD-055 and INF innovator on RA activity has been analysed within 14 week study period. DAS28-CRP(,4 CDAI and SDAI were evaluated. Additionally, safety data has been collected. Methods The study was conducted as international multicenter randomised double-blind placebo controlled study. The study enrolled 426 adults with active RA. Patients were randomised into 2 study arms in 2:1 ratio to receive BCD-055 or INF innovator in dose of 3 mg/kg. In the analysed period of the study, patients received the iv infusions on Wk0, Wk2, Wk6, Wk14. Results Efficacy: BCD-055 and INF innovator showed similar impact on RA activity: in both groups significant decline of DAS28-CRP(4 was observed (figure 1). This result corresponds to positive CDAI and SDAI dynamics (table 2). Medians of CDAI/SDAI on screening indicated high RA activity, while on Wk 14 – moderate activity. Analyses of inflammatory markers (ESR and C-reactive protein) revealed pronounced decline in ESR and CRP levels by Wk 2. No further elevation has been observed. Safety: No differences in safety profiles of BCD-055 and INF innovator has been shown. One of the most frequent AEs were arterial hypertension, anaemia, neutropenia and increase of transaminases. Number of patients with binding and neutralising antibodies also did not differ between groups. Babs were detected in 6.83% patients in BCD-055 arm and in 7.81% in INF innovator arm (p=0.888), Nab were observed in 1.61% and 0.78% patients in same arms (p=0.666). Conclusions Treatment with BCD-055 and INF innovator leads to significant decline in RA activity and inflammatory markers by Wk14, which corresponds with previous results of ACR20 assessment1. Both drugs are well tolerated with no differences in safety profiles. The frequency of ADA formation is also comparable. Reference [1] Denisov L, Gordeev I, Mazurov V, et al. FRI0208 Comparison of efficacy, safety and pharmacokinetics of infliximab biosimilar (BCD-055) and innovator infliximab Ann Rheum Dis2017;76:560–561. Disclosure of Interest A. Lila: None declared, L. Denisov: None declared, T. Plaksina: None declared, S. Smakotina: None declared, E. Kunder: None declared, N. Soroka: None declared, A. Kastanayan: None declared, O. Nesmeyanova: None declared, O. Antipova: None declared, E. Ilivanova: None declared, A. Eremeeva Employee of: JSC BIOCAD, E. Dokukina Employee of: JSC BIOCAD, E. Chernyaeva Employee of: JSC BIOCAD, R. Ivanov Employee of: JSC BIOCAD

Background Non-inferiority of BCD-055 in direct comparison to infliximab originator after 30 weeks of treatment in patients with ankylosing spondylitis (AS) was shown previously 1 . Here we present 54 week safety and efficacy data in ITT population from international double-blind randomised ASART-2 clinical trial. Objectives To compare BCD-055, proposed infliximab biosimilar and infliximab originator in terms of efficacy and safety in patients with AS. Methods Adult patients (n=199) aged 18–65 years, with active AS (BASDAIu003e4) received 5 mg/kg of BCD-055 (n=132) or infliximab (n=67) IV on w0, w2 and w6 and then every 8 w until w54. The results of the primary endpoint assessment (ASAS20 at w30) were presented earlier 1 . Secondary endpoints were proportion of patients, achieved ASAS20/40, and mean change from baseline in BASDAI, BASMI, BASFI, MASES, SF36 scores, chest excursion and TJC 44 at w54. Rate of AEs and proportion of patient with ADA to infliximab in both groups were also evaluated. Results The proportions of patients achieved ASAS20/ASAS40 were similar in both study groups at w54 (Abstract SAT0267 – figure 1). Improvement in AS symptoms showed similar dynamics in both groups: significant decrease in AS activity (BASDAI) and improvement in other secondary endpoints has developed within the first 14 weeks of treatment in both study groups and remained at achieved level until w54. The magnitude of changes of all evaluated parameters did not differ between groups. No statistically significant differences in rates of AEs were found between study groups (table 1). Most common reported AEs were infections, hematologic and vascular disorders, hypersensitivity reactions. Formation of ADA to infliximab was detected with similar frequency in both groups. Conclusions The 54 week results supports previously confirmed similar efficacy and safety of BCD-055, proposed infliximab biosimilar, and infliximab originator in patients with active AS. At all evaluated time points the efficacy as well as rate of AEs/SAEs did not differ between BCD-055 and infliximab originator groups. Reference [1] Denisov L, Gordeev I, Mazurov V, et al. FRI0208 Comparison of efficacy, safety and pharmacokinetics of infliximab biosimilar (BCD-055) and innovator infliximabAnn Rheum Dis2017;76:560–561. Disclosure of Interest L. Denisov: None declared, P. Shesternya: None declared, T. Plaksina: None declared, T. Kropotina: None declared, N. Soroka: None declared, E. Kunder: None declared, A. Lutskii Employee of: JSC BIOCAD, A. Eremeeva Employee of: JSC BIOCAD, E. Dokukina Employee of: JSC BIOCAD, E. Chernyaeva Employee of: JSC BIOCAD, R. Ivanov Employee of: JSC BIOCAD, V. Mazurov: None declared

Background Infliximab (IFX) was one of the first genetically engineered biologics successfully applied for medical use in patients with active RA and patients with AS. Previous preclinical studies showed that BCD-055 is highly similar to innovator IFX. Objectives This abstract presents results from three clinical trials of infliximab biosimilar, BCD-055, including comparative data on pharmacokinetics (PK), efficacy and safety in a variety of patient populations. Methods All three studies were conducted as international multicenter randomized double-blind studies in direct comparison with innovator IFX. ASART-1 study (Phase 1, PK study) and ASART-2 study (Phase 3, efficacy and safety study) were conducted in patients with AS. After the screening patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV on day 1 wk 0, 2, 6 and then every 8 wks (up to wk 54). LIRA study (Phase 3 study) was conducted in patients with active RA who were stratified by age and DAS28 score, randomized (2:1) into 2 arms and received BCD-055 or innovator IFX at a dose 3 mg/kg IV on day 1 wk 0, 2, 6 and then every 8 wks (up to wk 54). Results A total of 91 patients were enrolled in ASART-1 study, 198 patients - in ASART-2 study and 195 patients - in LIRA study in Russia and Belarus. PK characteristics were equivalent for BCD-055 and innovator IFX. After the single administration 90%CI for the ratio of geometric means for AUC0–336 was 86.40% – 110.09%, for Cmax – 82.70% – 109.83%. After multiple-dose administration 90%CI for the ratio of geometric means for AUC0-tau was 81.35% – 121.13%, for Cmax,ss – 90.16% – 117.32%. Efficacy: BCD-055 is non-inferior to innovator IFX both in RA and AS patients: ACR20 at wk 14 was reached by 75.83% of patients in BCD-055 group and 74.19% in innovator IFX group (p=0.951, 95% CI for difference in proportion [-12.90%; 16.18%], margin -20%), ASAS20 at wk 30 - by 81.30% and 67.74% respectively (p=0.061, 95% CI for difference in proportion [-1.18%; 28.28%], margin -17.5%). Safety: BCD-055 and innovator IFX showed highly similar safety profiles in all three studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and varied from 47% in patients with AS to 53% in patients with RA. Immunogenicity assessment didn9t find any significant difference between BCD-055 and innovator IFX, anti-drug antibodies occurred at the same rate irrespectively to the group. Conclusions BCD-055 is highly similar to innovator IFX in patients with active RA and in patients with AS in terms of efficacy, safety and PK. References EMA/CHMP/BMWP/403543/2010. Disclosure of Interest L. Denisov: None declared, I. Gordeev: None declared, V. Mazurov: None declared, A. Lila: None declared, E. Zonova: None declared, O. Nesmeyanova: None declared, E. Ilivanova: None declared, T. Plaksina: None declared, A. Eremeeva Employee of: JCS BIOCAD, A. Artemeva Employee of: JCS BIOCAD, E. Chernyaeva Employee of: JCS BIOCAD, R. Ivanov Employee of: JCS BIOCAD, S. Pimanov: None declared, E. Kunder: None declared, N. Soroka: None declared

The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera), a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia®) (the BIORA study) in patients with rheumatoid arthritis (RA) refractory to therapy with tumor necrosis factor- а inhibitors. Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability. Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1): 1) the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2) those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1) with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia®) or Group AM (that was MabThera®), the similar methodology was followed in Group 2 (Groups MM and MA). Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks. Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50) and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773), which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment outcomes.