EFFICACY AND SAFETY OF IFX-1, AN ANTI-C5A MONOCLONAL ANTIBODY, IN AN OPEN-LABEL, PHASE 2A STUDY IN PATIENTS WITH SEVERE HIDRADENITIS SUPPURATIVA NOT ELIGIBLE FOR ADALIMUMAB Evangelos J. Giamarellos-Bourboulis 1, Maria Argyropoulou 1, Theodora Kanni 1, Isabell Kopka 2, Othmar Zenker 2 1 Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece 2 InflaRx GmbH, Jena, Germany
DISCLOSURE OF INTERESTS Evangelos Giamarellos-Bourboulis has received honoraria (paid to the University of Athens) from AbbVie, Biotest, Brahms GmbH, and The Medicines Company; has received compensation as a consultant for Astellas Greece, InflaRx GmbH, Germany and for XBiotech (paid to the University of Athens); and has received independent educational grants (paid to the University of Athens) from AbbVie and Sanofi. He is funded by the FrameWork 7 program HemoSpec (granted to the University of Athens) and by the Horizon2020 Marie-Curie Grant European Sepsis Academy (granted to the University of Athens). Maria Argyropoulou does not have any conflict of interest to disclose. Theodora Kanni has received honorarium from Xbiotech. Isabell Kopka and Othmar Zenker are employees at InflaRx GmbH, Germany. Page 2
BACKGROUND 1 C5A is increased in hidradenitis suppurativa (HS) Page 3 Kanni T, et al. Br J Dermatol doi: 10.1111/bjd.16428
BACKGROUND 2 C5a is associated with severity Page 4 Kanni T, et al. Br J Dermatol doi: 10.1111/bjd.16428
BACKGROUND 3 Plasma C5a primes monocyte TNFα production and is inhibited by IFX-1 Page 5 Kanni T, et al. Br J Dermatol doi: 10.1111/bjd.16428
IFX-1 HUMANIZED MONOCLONAL IGG4Κ ANTIBODY THAT SPECIFICALLY BINDS TO THE SOLUBLE HUMAN COMPLEMENT SPLIT PRODUCT C5A Page 6
MODE OF ACTION OF IFX-1 Page 7
INCLUSION CRITERIA Written informed consent provided by the patient Age 18 years Diagnosis of HS for at least 1 year HS lesions in at least 2 distinct anatomic areas, one of which Hurley Stage II or III Total AN (abscesses and nodules) count 3 Primary or secondary failure of anti-tnf (tumor necrosis factor) treatment or non-eligibility for adalimumab Failure of previous antimicrobial treatments Page 8
EXCLUSION CRITERIA 1 Body weight >150kg >30 draining fistulas Administration of antimicrobials the last 30 days Administration of any biological compound the last 6 months Administration of corticosteroids the last 3 weeks Any active infection Severe congestive heart failure Any autoimmune or immunodeficiency disorder Page 9
EXCLUSION CRITERIA 2 History of hematological or solid tumor malignancy Neutrophil count <1000/mm 3 Serum creatinine >3 the upper normal Total bilirubin or serum aminotransferases >2 the upper normal Hepatitis B or C or HIV infection Pregnancy or lactation Page 10
STUDY DESIGN Screening Duration: 2 weeks Total enrolled: 12 subjects Open-label Period With 800mg IFX-1 Duration: 8 weeks Assessments: Day 1, 4, 8, 15, 22, 29, 36, 43, 50 Follow-up Period Duration: 12 weeks Assessments: Day 78, 108, 134 Page 11
STUDY OBJECTIVES Primary endpoint: SAFETY Safety and tolerability of IFX-1 administered over 8 weeks in moderate to severe HS Adverse Events Secondary endpoints: EFFICACY HS clinical response (HiSCR) HS Physician s Global Assessment (PGA) Abscesses and nodules (AN) count; lesion dimensions C5a levels Page 12
DEMOGRAPHIC & BASELINE CHARACTERISTICS Parameter Overall N = 12 Male subjects, number (%) 8 (66.7) Age [years], mean (SD) 48.3 (14.7) Body mass index [kg/m 2 ], mean (SD) 27.3 (4.9) Weight [kg], mean (SD) 82.2 (14.7) Duration of HS [years], mean (SD) 20 (9) Subjects with Hurley Stage III, number (%) 12 (100) Abscesses and nodules count, mean (SD) 6.4 (2.5) Subjects with failure to TNF-alpha blockade, number (%) 9 (75.0) Page 13
OVERVIEW OF ADVERSE EVENTS Subjects (%) Category Total = 12 Any Adverse Event (AE) 6 (50.0) 9 Severe 4 (33.3) 5 a Mild 2 (16.7) 4 Any related AE 0 0 Any serious AE 4 (33.3) 5 a Severe 4 (33.3) 5 Number of Events Any AE leading to drug withdrawal 1 (8.3) 1 Resolved AEs 8 b Any fatal AE 0 0 AE = adverse event; a Two AEs occurred during the follow-up period. b The only unresolved AE was 1 mild AE of Depression during the follow-up period. Page 14
HS CLINICAL RESPONSE (HiSCR) Open-label treatment Follow-up period * p < 0.05 compared with day 22 ** p = 0.09 compared with day 50 Page 15
CHANGE OF ABSCESSES & NODULES COUNT Open-label treatment Follow-up period Page 16
CHANGE OF LESION DIMENSIONS Open-label treatment Follow-up period Page 17
HS PHYSICIAN S GLOBAL ASSESSMENT Open-label treatment Follow-up period Page 18
PATIENT 11 Before start of IFX-1 Day 50: end of treatment Day 134: end of follow-up
C5A LEVELS Open-label treatment Follow-up period Page 20
CONCLUSIONS SAFETY IFX-1 was well-tolerated AEs were HS-associated EFFICACY 75% HiSCR responders at the end of treatment 83% HiSCR responders at the end of follow-up (84 days after end of the treatment period) Page 21