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Background:Previously, the results of phase II AURORA clinical study of levilimab in subjects with active rheumatoid arthritis (RA) have been reported1. Here we report topline 24-weeks results of preliminary primary efficacy and safety analysis of phase 3 double-blind, placebo-controlled randomized clinical study (SOLAR).Objectives:To confirm that levilimab in combination with methotrexate is superior to placebo in combination with methotrexate in achieving ACR20 at week 12 and low disease activity (LDA) at week 24 in subjects with methotrexate (MTX) resistant active RA.Methods:The study is ongoing at 21 clinical sites in Russia and Belarus. All randomized subjects have completed 24 weeks of study between November 2019 and January 2021.154 adults, aged ≥18 years with the diagnosis of RA (ACR 2010) for at least 24 weeks, and confirmed disease activity at screening despite treatment with MTX for the last 12 weeks (in a stable dose 15-25 mg/week, for at least 4 weeks) were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52). The randomization and treatment allocation were carried out by a central computer-based system. Subjects, caregivers, and those assessing the outcomes were blinded to group assignment.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy outcomes: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved LDA of RA (DAS28-CRP For ethical reasons, subjects who haven’t achieved minimal clinical response at week 12 (≥20% reduction in the number of tender/swollen joints; 66/68) received rescue therapy at the discretion of the Investigator, and all subsequent efficacy assessments for those were considered missing.For the primary efficacy analysis, subjects with missing data due to study discontinuation or rescue therapy prescription were considered non-responders (non-responder imputation, NRI). Otherwise, the analysis was performed on observed cases.Safety was assessed through monitoring of adverse events (AEs).Results:The primary analysis was based on 149 randomized subjects (n=99 and n = 50) for ACR20 and 154 randomized subjects (n= 102 and n = 52) for LDA.70/99 (71%) of subjects who received levilimab and 20/50 (40%) who received placebo achieved ACR20 response at week 12. The difference in proportion was 30% with a lower bound of 97.5% CI 12.8%; p=0.0003 (Pearson’s chi-squared test).53/102 (52%) of subjects received levilimab and 3/52 (6%) received placebo achieved LDA at week 24. The difference in proportion was 46% with a lower bound of 97.5% CI 31.2 %; pThe safety population included all subjects, who received investigational product (n=154).The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were: blood cholesterol increase (19% vs. 10%), ALT increase (11% vs. 8%), lymphocyte count decrease (9% vs. 8%), blood bilirubin increase (11% vs. 0%), blood triglycerides increase (9% vs. 2%), AST increase (7% vs. 4%), IGRA with M.tuberculosis antigen positive (5% vs. 6%), ANC decrease (8% vs. 0%). No deaths were occurred.Conclusion:The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. No new safety signals were detected.Trial registration: Clinicaltrials.gov identifier NCT04397562References:[1]Mazurov V, Zotkin E, Ilivanova E, et al. FRI0114 EFFICACY OF LEVILIMAB, NOVEL MONOCLONAL ANTI-IL-6 RECEPTOR ANTIBODY, IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 1-YEAR RESULTS OF PHASE 2 AURORA STUDY. Annals of the Rheumatic Diseases 2020;79:637-638.Acknowledgements:We thank all contributors to the SOLAR clinical trialDisclosure of Interests:V Mazurov: None declared, Maxim Korolev: None declared, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Aleksander Kastanayan: None declared, Tatyana Povarova: None declared, Tatyana Plaksina: None declared, Olga Antipova: None declared, Diana Kretchikova: None declared, Svetlana Smakotina: None declared, Oksana Tciupa: None declared, Tatiana Raskina: None declared, Tatyana Kropotina: None declared, Olga Nesmeyanova: None declared, Tatiana Popova: None declared, Ekaterina Dokukina Employee of: JSC BIOCAD, Aleksandra Plotnikova Employee of: JSC BIOCAD, Anton Lutskii Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD

Background: In the previous phase 1 study BCD-089 (INN: levilimab) was well-tolerated, had favorable safety profile and low immunogenicity1. Here we report 12-week efficacy and safety results of ongoing phase 2 clinical study of BCD-089 in patients with active RA. Objectives: This study is aimed to assess efficacy and safety of 2 dosing regimens of BCD-089 in patients with MTX-IR active RA. Methods: During this multicenter double-blind placebo-controlled randomized clinical study (NCT03455842) 105 MTX-IR patients with active RA (ACR2010) were assigned (1:1:1) to receive 162 mg of BCD-089 s.c. (QW arm and Q2W arm) or PBO. MTX (10-25 mg/week) was used in all groups. After completion of 12-week blinded period patients from QW/Q2W arms continued the treatment, patients from PBO arm were switched to BCD-089 Q2W until Wk56. The primary efficacy endpoint was the rate of ACR20 at Wk12. Secondary endpoints included ACR50/70 and DAS28-CRP(4). The safety was routinely evaluated. Results: The efficacy analysis showed that 95% confidence interval for BCD-089 treatment effect relative to PBO was [38.45 – 81.55] for QW arm and [16.53 – 63.4] for Q2W arm, which confirms the superiority to PBO of either dosing regimens. Summary of efficacy results is presented in table 1. The majority of adverse events (AE) were laboratory abnormalities. The spectrum of AEs is similar to other IL6R inhibitors (Table 2). Three serious AE (SAEs) were reported: community-acquired pneumonia (QW arm, treatment-related), acute cholecystitis (PBO arm, not related, did not lead to treatment discontinuation), and acute heart failure leading to death (Q2W arm, not related). One case of moderate local reaction (erythema) was reported in QW arm. Conclusion: BCD-089 in combination with MTX had superior efficacy compared with MTX plus PBO in MTX-IR patients with active RA. BCD-089 showed safety profile consistent with other IL6R inhibitors. Further clinical studies are needed. Reference: [1] Khlyabova P, et al. doi: 10.1136/annrheumdis-2018-eular.2410 Disclosure of Interests: V Mazurov Grant/research support from: JSC BIOCAD, Evgeniy Zotkin: None declared, Elena Ilivanova Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Nikolaj Soroka: None declared, Alena Kundzer: None declared, Anton Lutskii Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Ekaterina Chernyaeva Employee of: JSC BIOCAD, Roman Ivanov Employee of: JSC BIOCAD

Background Efficacy and safety of netakimab (NTK), a humanized anti-IL17A antibody, was established in phase 2 clinical trials in patients (pts) with radiographic axial spondyloarthritis (r-axSpA)1 and psoriasis2. Objectives The abstract presents 16-week data from ongoing ASTERA study (NCT03447704) in pts with active r-axSpA. Methods ASTERA is a phase 3 international double-blind placebo (PBO)-controlled study. 228 adult pts with r-axSpA, active (BASDAI ≥ 4) despite the standard NSAIDs, were randomly assigned (1:1) to receive 120 mg NTK or PBO SC at Week (Wk) 0,1,2 and then q2w through Wk 16. After Wk 16 all pts will start to receive NTK up to Wk 52. Primary endpoint was ASAS40 rate at Wk 16. Results The mean age at baseline was 39.14±9.9 years, the mean symptoms duration was 4.3±4.5 years. 76.8% of pts were naive to biological treatment. At Wk 16 ASAS40 rate was higher in NTK arm compared to PBO: 40.35% versus (vs.) 2.63% pts (95% CI for the difference in ASAS40 rate was [27.37%; 48.07%] (p Conclusion NTK at a dose 120 mg is well-tolerated drug with favorable safety profile that leads to decline in r-axSpA activity, function improvement and axial mobility in 16 Wks. References [1] Mazurov V, et al. Ann Rheum Dis 2018;77:A64. 2Samtsov A, et al. Vestn Dermatol Venerol 2017;0(5):52-63. Disclosure of Interests Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: paiment from Pfizer, Novartis, Abbvie, Biocad, Selgene, MSD, Sanofy does not exceed 10 000 euros, V Mazurov Grant/research support from: JSC BIOCAD, Shandor Erdes Grant/research support from: JSC BIOCAD, Speakers bureau: JSC BIOCAD, Tatiana Dubinina: None declared, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Elena Ilivanova Grant/research support from: JSC BIOCAD, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Aleksander Kastanayan Grant/research support from: JSC BIOCAD, Tatyana Povarova Grant/research support from: JSC BIOCAD, Elena Zhugrova Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Pavel Shesternya Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Olga Antipova Grant/research support from: JSC BIOCAD, Elena Smolyarchuk Grant/research support from: JSC BIOCAD, Oksana Tciupa Grant/research support from: JSC BIOCAD, Diana Abdulganieva: None declared, Diana Kretchikova Grant/research support from: JSC BIOCAD, Ivan Gordeev Grant/research support from: JSC BIOCAD, Vadim Tyrenko Grant/research support from: JSC BIOCAD, Aleksandra Strelkova Grant/research support from: JSC BIOCAD, Anna Eremeeva Grant/research support from: JSC BIOCAD, Ekaterina Chernyaeva Employee of: JSC BIOCAD, Roman Ivanov Employee of: JSC BIOCAD

Background:Previously, 12-week results of phase 2 clinical study of levilimab (LVL) in patients with active rheumatoid arthritis (RA) have been reported1. The study has met the primary endpoint at W12 confirming that treatment with LVL 162 mg SC + methotrexate (MTX) either QW or Q2W is superior to MTX alone in patients with RA and inadequate response to methotrexate (MTX-IR). Here we report 1-year efficacy and safety data in QW and Q2W arm of the study.Objectives:This study was aimed to assess the efficacy and safety of 2 dosing regimens of LVL in active MTX-IR RA subjects.Methods:This multicenter double-blind placebo-controlled study (NCT03455842) enrolled 105 MTX-IR subjects with active RA (ACR2010). The study design is outlined on Figure 1. Secondary endpoints for the open-label period included ACR20/50/70, LDA, remission rates, and DAS28-CRP(4), among others. The safety was evaluated up to W56.Figure 1.Study designResults:At W12 ACR20 was reached by 77.1% and 57.1% of subjects of QW and Q2W arms respectively. Within open-label (OLE) period further increase in clinical response degree was observed up to W52, more pronounced in ACR50 and even more in ACR70 / RA LDA and Remission rates (Table 1). Figure 1 summarizes the dynamic of DAS28-CRP(4) change throughout the study. QW regimen showed better efficacy results.Table 1.Efficacy results (full analysis set), n (%).QW + MTX(n = 35)Q2W + MTX(n = 35)p-valueACR20 W1227 (77.1)20 (57.1)0.07 W5232 (91.4)25 (71.4)0.03ACR50 W1218 (51.4)11 (31.4)0.09 W5226 (74.3)23 (65.7)0.43ACR70 W1210 (28.6)7 (20.0)0.40 W5223 (65.7)16 (45.7)0.09LDA (DAS28 20 (57.1)10 (28.6)0.02 W5229 (82.9)24 (68.6)0.16EULAR Remission W244 (11.4)2 (5.7)0.67 W5210 (28.6)10 (28.6)1.00Table 2 shows the main safety endpoints for the entire study (W0 – W56). The most common treatment related AEs (registered >5% of subjects) were laboratory abnormalities (neutrophil count decrease, ALT / AST increase, blood cholesterol/triglycerides increased). SAE occurred within the blinded study period were reported previously1. During OLE, starting from W12, four new serious AE (SAEs) were reported: 3 in LVL QW arm: haemorrhage (gr.3, unrelated), vaginal cyst (gr.3, unrelated) and keratitis (gr.2, unrelated); 1 in LVL Q2W arm: myocardial ischemia with cardiovascular insufficiency (gr.5, unrelated).Table 2.Safety results (full analysis set, W0 – W56), n (%).QW + MTX(n = 35)Q2W + MTX(n = 35)Any TEAEs/SAEs34 (97.1)29 (82.9)Any SAEs4 (11.4)2 (5.7)Any gr. 3-4 AEs16 (45.7)12 (34.3)Gr. 3-4 neutropenia4 (11.4)5 (14.3)AEs of special interest(ALT / AST high; Leucopenia / Neutropenia; Infections; Cholesterol/triglycerides high)28 (80.0)26 (74.3)Treatment discontinuation due to AE04 (11.3)Deaths02 (5.7) (unrelated)Conclusion:Within 1 year of treatment LVL + MTX showed sustained efficacy, with continuous clinical improvement in MTX-IR subjects with active RA. The safety profile of LVL was consistent with other IL6R inhibitors. LVL QW regimen was shown to be safe with better efficacy in terms of time and magnitude and was selected for phase 3 confirmatory clinical study.References:[1]http://dx.doi.org/10.1136/annrheumdis-2019-eular.7220Figure 2.Absolute DAS-28-CRP(4) change (median ± IQR, full analysis set)Disclosure of Interests:V Mazurov: None declared, Evgeniy Zotkin: None declared, Elena Ilivanova Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Nikolaj Soroka Grant/research support from: JSC BIOCAD, Alena Kundzer: None declared, Anton Lutskii Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD, Arina Zinkina-Orihan 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 previously1. 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 (BASDAI>4) 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 earlier1. Secondary endpoints were proportion of patients, achieved ASAS20/40, and mean change from baseline in BASDAI, BASMI, BASFI, MASES, SF36 scores, chest excursion and TJC44 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