BIMZELX 320mg 320mg / 2ml injection for pre-filled pen medication leaflet

Bimzelx 320 mg solution for injection in pre-filled syringe

Bimzelx 320 mg solution for injection in pre-filled pen

Each pre-filled syringe contains 160 mg of bimekizumab in 1 mL.

Bimzelx 320 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 320 mg of bimekizumab in 2 mL.

Each pre-filled pen contains 160 mg of bimekizumab in 1 mL.

Bimzelx 320 mg solution for injection in pre-filled pen

Each pre-filled pen contains 320 mg of bimekizumab in 2 mL

Bimekizumab is a humanised IgG1monoclonal antibody produced in a genetically engineered Chinesehamster ovary (CHO) cell line by recombinant DNA technology.

For the full list of excipients, see section 6.1.

Solution for injection (injection)

The solution is clear to slightly opalescent and, colourless to pale brownish-yellow.

Plaque psoriasis

Bimzelx is indicated for the treatment of moderate to severe plaque psoriasis in adults who arecandidates for systemic therapy.

Bimzelx, alone or in combination with methotrexate, is indicated for the treatment of active psoriaticarthritis in adults who have had an inadequate response or who have been intolerant to one or moredisease-modifying antirheumatic drugs (DMARDs).

Non-radiographic axial spondyloarthritis (nr-axSpA)

Bimzelx is indicated for the treatment of adults with active non-radiographic axial spondyloarthritiswith objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/ormagnetic resonance imaging (MRI) who have responded inadequately or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).

Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)

Bimzelx is indicated for the treatment of adults with active ankylosing spondylitis who haveresponded inadequately or are intolerant to conventional therapy.

Bimzelx is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acneinversa) in adults with an inadequate response to conventional systemic HS therapy (see section 5.1).

Bimzelx is intended for use under the guidance and supervision of a physician experienced in thediagnosis and treatment of conditions for which Bimzelx is indicated.

Plaque psoriasis

The recommended dose for adult patients with plaque psoriasis is 320 mg (given as 2 subcutaneousinjections of 160 mg or 1 subcutaneous injection of 320 mg) at week 0, 4, 8, 12, 16 and every 8 weeksthereafter.

The recommended dose for adult patients with active psoriatic arthritis is 160 mg (given as1 subcutaneous injection of 160 mg) every 4 weeks.

For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, the recommendeddose is the same as for plaque psoriasis [320 mg (given as 2 subcutaneous injections of 160 mg or1 subcutaneous injection of 320 mg) at week 0, 4, 8, 12, 16 and every 8 weeks thereafter]. After 16weeks, regular assessment of efficacy is recommended and if a sufficient clinical response in jointscannot be maintained, a switch to 160 mg every 4 weeks can be considered.

Axial spondyloarthritis (nr-axSpA and AS)

The recommended dose for adult patients with axial spondyloarthritis is 160 mg (given as1 subcutaneous injection of 160 mg) every 4 weeks.

The recommended dose for adult patients with hidradenitis suppurativa is 320 mg (given as2 subcutaneous injections of 160 mg or 1 subcutaneous injection of 320 mg) every 2 weeks up to week16 and every 4 weeks thereafter.

For above indications, consideration should be given to discontinuing treatment in patients who haveshown no improvement by 16 weeks of treatment.

Overweight patients with plaque psoriasis

For some patients with plaque psoriasis (including psoriatic arthritis with coexistent moderate tosevere psoriasis) and a body weight ≥120 kg who did not achieve complete skin clearance at week 16,320 mg every 4 weeks after week 16 may further improve treatment response (see section 5.1).

Elderly (≥65 years)

No dose adjustment is required (see section 5.2).

Bimekizumab has not been studied in these patient populations. Dose adjustments are not considerednecessary based on pharmacokinetics (see section 5.2).

The safety and efficacy of bimekizumab in children and adolescents below the age of 18 years havenot been established. No data are available.

This medicinal product is administered by subcutaneous injection. A 320 mg dose can be given as2 subcutaneous injections of 160 mg or 1 subcutaneous injection of 320 mg.

Suitable areas for injection include thigh, abdomen and upper arm. Injection sites should be rotatedand injections should not be given into psoriasis plaques or areas where the skin is tender, bruised,erythematous, or indurated. Administration in the upper arm may only be performed by a healthcareprofessional or caregiver.

The pre-filled syringe or pre-filled pen must not be shaken.

After proper training in subcutaneous injection technique, patients may self-inject Bimzelx with a pre-filled syringe or pre-filled pen if their physician determines that it is appropriate and with medicalfollow-up as necessary. Patients should be instructed to inject the full amount of Bimzelx according tothe instructions for use provided in the package leaflet.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important active infections (e.g. active tuberculosis, see section 4.4).

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

Bimekizumab may increase the risk of infections such as upper respiratory tract infections and oralcandidiasis (see section 4.8).

Caution should be exercised when considering the use of bimekizumab in patients with a chronicinfection or a history of recurrent infection. Treatment with bimekizumab must not be initiated inpatients with any clinically important active infection until the infection resolves or is adequatelytreated (see section 4.3).

Patients treated with bimekizumab should be instructed to seek medical advice if signs or symptomssuggestive of an infection occur. If a patient develops an infection, the patient should be carefullymonitored. If the infection becomes serious or is not responding to standard therapy, treatment shouldbe discontinued until the infection resolves.

Prior to initiating treatment with bimekizumab, patients should be evaluated for TB infection.

Bimekizumab should not be given in patients with active TB (see section 4.3). Patients receivingbimekizumab should be monitored for signs and symptoms of active TB. Anti-TB therapy should beconsidered prior to initiating bimekizumab in patients with a past history of latent or active TB inwhom an adequate course of treatment cannot be confirmed.

Cases of new or exacerbations of inflammatory bowel disease have been reported with bimekizumab(see section 4.8). Bimekizumab is not recommended in patients with inflammatory bowel disease. If apatient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation ofpre-existing inflammatory bowel disease, bimekizumab should be discontinued and appropriatemedical management should be initiated.

Serious hypersensitivity reactions including anaphylactic reactions have been observed with IL-17inhibitors. If a serious hypersensitivity reaction occurs, administration of bimekizumab should bediscontinued immediately and appropriate therapy initiated.

Prior to initiating therapy with bimekizumab, completion of all age appropriate immunisationsaccording to current immunisation guidelines should be considered.

Live vaccines should not be given in patients treated with bimekizumab.

Patients treated with bimekizumab may receive inactivated or non-live vaccinations. Healthyindividuals who received a single 320 mg dose of bimekizumab two weeks prior to vaccination withan inactivated seasonal influenza vaccine had similar antibody responses compared to individuals whodid not receive bimekizumab prior to vaccination.

This medicinal product contains 0.4 mg of polysorbate 80 in each 1 mL solution. Polysorbates maycause allergic reactions.

This medicinal product contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially“sodium free”.

No interaction studies have been performed.

There is no direct evidence for the role of IL-17A or IL-17F in the expression of CYP450 enzymes.

The formation of some CYP450 enzymes is suppressed by increased levels of cytokines duringchronic inflammation. Thus, anti-inflammatory treatments, such as with the IL-17A and IL-17Finhibitor bimekizumab, may result in normalisation of CYP450 levels with accompanying lowerexposure of CYP450-metabolised medicinal products. Therefore, a clinically relevant effect on

CYP450 substrates with a narrow therapeutic index, in which the dose is individually adjusted (e.g.warfarin) cannot be excluded. On initiation of bimekizumab therapy in patients being treated withthese types of medicinal products, therapeutic monitoring should be considered.

Population pharmacokinetic (PK) data analyses indicated that concomitant administration ofconventional disease modifying antirheumatic drugs (cDMARDs) including methotrexate or priorexposure to biologics have no clinically relevant impact on the clearance of bimekizumab.

Live vaccines should not be given concurrently with bimekizumab (see section 4.4).

Women of childbearing potential should use an effective method of contraception during treatmentand for at least 17 weeks after treatment.

There is a limited amount of data on the use of bimekizumab in pregnant women. Animal studies donot indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetaldevelopment, parturition or postnatal development (see section 5.3). As a precautionary measure, it ispreferable to avoid the use of Bimzelx during pregnancy.

It is unknown whether bimekizumab is excreted in human milk. A risk to the newborn/infant cannotbe excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstainfrom Bimzelx therapy taking into account the benefit of breast-feeding for the child and the benefit oftherapy for the woman.

The effect of bimekizumab on human fertility has not been evaluated. Animal studies do not indicatedirect or indirect harmful effects with respect to fertility (see section 5.3).

Bimzelx has no or negligible influence on the ability to drive and use machines.

The most frequently reported adverse reactions were upper respiratory tract infections (14.5%, 14.6%,16.3%, 8.8% in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis (axSpA) and hidradenitissuppurativa respectively) and oral candidiasis (7.3%, 2.3%, 3.7%, 5.6% in PSO, PsA, axSpA and HSrespectively).

Adverse reactions from clinical studies and post-marketing reports (Table 1) are classified by

MedDRA System Organ Class and frequency, using the following convention: very common (≥ 1/10),common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), veryrare (< 1/10,000), not known (cannot be estimated from the available data).

A total of 5862 patients have been treated with bimekizumab in blinded and open-label clinical studiesin plaque psoriasis (PSO), psoriatic arthritis (PsA), axial spondyloarthritis (nr-axSpA and AS) andhidradenitis suppurativa (HS) representing 11468.6 patient-years of exposure. Of these, over 4660patients were exposed to bimekizumab for at least one year. Overall, the safety profile ofbimekizumab is consistent across all indications.

Table 1: List of adverse reactions

System Organ Class Frequency Adverse reaction

Infections and infestations Very common Upper respiratory tract infections

Common Oral candidiasis,

Tinea infections,

Ear infections,

Herpes simplex infections,

Oropharyngeal candidiasis,

Gastroenteritis,

Folliculitis,

Vulvovaginal mycotic infection (includingvulvovaginal candidiasis)

Uncommon Mucosal and cutaneous candidiasis(including oesophageal candidiasis),

Conjunctivitis

Blood and lymphatic system Uncommon Neutropeniadisorders

Nervous System disorders Common Headache

Gastrointestinal disorders Uncommon Inflammatory bowel disease

Skin and subcutaneous tissue Common Rash, dermatitis and eczema,disorders Acne

General disorders and Common Injection site reactionsa,administration site conditions Fatiguea) Includes: injection site erythema, reaction, oedema, pain, swelling, haematoma.

In the placebo-controlled period of Phase III clinical studies in plaque psoriasis, infections werereported in 36.0% of patients treated with bimekizumab for up to 16 weeks compared with 22.5% ofpatients treated with placebo. Serious infections occurred in 0.3% of patients treated withbimekizumab and 0% treated with placebo.

The majority of infections consisted of non-serious mild to moderate upper respiratory tract infectionssuch as nasopharyngitis. There were higher rates of oral and oropharyngeal candidiasis in patientstreated with bimekizumab consistent with the mechanism of action (7.3% and 1.2% respectivelycompared to 0% for placebo-treated patients). More than 98% of cases were non-serious, mild ormoderate in severity, and did not require treatment discontinuation. A slightly higher incidence of oralcandidiasis was reported in patients <70 kg (8.5% versus 7.0% in patients ≥70 kg).

Over the entire treatment period of Phase III studies in plaque psoriasis, infections were reported in63.2% of patients treated with bimekizumab (120.4 per 100 patient-years). Serious infections werereported in 1.5% of patients treated with bimekizumab (1.6 per 100 patient-years) (see section 4.4).

Infection rates observed in PsA and axSpA (nr-axSpA and AS) Phase III clinical studies were similarto those observed in plaque psoriasis apart from oral and oropharyngeal candidiasis rates in patientstreated with bimekizumab, which were lower at 2.3% and 0% respectively in PsA and 3.7% and 0.3%respectively in axSpA compared to 0% with placebo.

Infection rates observed in HS Phase III clinical studies were similar to those observed in otherindications. In the placebo-controlled period, oral and oropharyngeal candidiasis rates in patientstreated with bimekizumab were 7.1% and 0% respectively compared to 0% with placebo.

Neutropenia was observed with bimekizumab in Phase III clinical studies in plaque psoriasis. Over theentire treatment period of Phase III studies, neutropenia grade 3/4 were observed in 1% of patientstreated with bimekizumab.

The frequency of neutropenia in PsA, axSpA (nr-axSpA and AS) and HS clinical studies was similarto that observed in plaque psoriasis studies.

Most cases were transient and did not require treatment discontinuation. No serious infections wereassociated with neutropenia.

Serious hypersensitivity reactions including anaphylactic reactions have been observed with IL-17inhibitors.

Plaque psoriasis

Approximately 45% of plaque psoriasis patients treated with bimekizumab up to 56 weeks at therecommended dosing regimen (320 mg every 4 weeks up to week 16 and 320 mg every 8 weeksthereafter) developed anti-drug antibodies. Of the patients who developed anti-drug antibodies,approximately 34% (16% of all patients treated with bimekizumab) had antibodies that were classifiedas neutralising.

Approximately 31% of patients with psoriatic arthritis treated with bimekizumab at the recommendeddosing regimen (160 mg every 4 weeks) up to 16 weeks had anti-drug antibodies. Of the patients withanti-drug antibodies, about 33% (10% of all patients treated with bimekizumab) had antibodies thatwere classified as neutralising. By week 52, approximately 47% of biologic disease-modifying anti-rheumatic drug (bDMARD) treatment naïve patients with psoriatic arthritis in the BE OPTIMALstudy treated with bimekizumab at the recommended dosing regimen (160 mg every 4 weeks) hadanti-drug antibodies. Of the patients with anti-drug antibodies, about 38% (18% of all patients in the

BE OPTIMAL study treated with bimekizumab) had antibodies that were classified as neutralising.

Axial spondyloarthritis (nr-axSpA and AS)

Approximately 57% of patients with nr-axSpA treated with bimekizumab up to 52 weeks at therecommended dosing regimen (160 mg every 4 weeks) had anti-drug antibodies. Of the patients withanti-drug antibodies, approximately 44% (25% of all patients treated with bimekizumab) hadantibodies that were classified as neutralising.

Approximately 44% of patients with AS treated with bimekizumab up to 52 weeks at therecommended dosing regimen (160 mg every 4 weeks) had anti-drug antibodies. Of the patients withanti-drug antibodies, approximately 44% (20% of all patients treated with bimekizumab) hadantibodies that were classified as neutralising.

Approximately 59% of HS patients treated with bimekizumab up to 48 weeks at the recommendeddosing regimen (320 mg every 2 weeks up to week 16 and 320 mg every 4 weeks thereafter)developed anti-drug antibodies. Of the patients who developed anti-drug antibodies, approximately63% (37% of all patients treated with bimekizumab) had antibodies that were classified asneutralising.

Across indications, no clinically meaningful impact on clinical response was associated with anti-bimekizumab antibodies development and an association between immunogenicity and treatmentemergent adverse events has not been clearly established.

Exposure is limited in elderly subjects.

Elderly patients may be more likely to experience certain adverse reactions such as oral candidiasis,dermatitis and eczema when using bimekizumab.

In the placebo-controlled period of Phase III clinical studies in plaque psoriasis, oral candidiasis wasobserved in 18.2% of patients ≥65 years versus 6.3% in <65 years, dermatitis and eczema in 7.3% ofpatients ≥65 years versus 2.8% in <65 years.

In the placebo-controlled period of Phase III clinical studies in psoriatic arthritis, oral candidiasis wasobserved in 7.0% of patients ≥65 years versus 1.6% in <65 years, dermatitis and eczema in 1.2% ofpatients ≥65 years versus 2.0% in <65 years.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Single doses of 640 mg intravenously or 640 mg subcutaneously, followed by 320 mg subcutaneouslyevery two weeks for five doses have been administered in clinical studies without dose-limitingtoxicity. In the event of overdose, it is recommended that the patient be monitored for any signs andsymptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC21

Bimekizumab is a humanised IgG1/κ monoclonal antibody that selectively binds with high affinity to

IL-17A, IL-17F and IL-17AF cytokines, blocking their interaction with the IL-17RA/IL-17RCreceptor complex. Elevated concentrations of IL-17A and IL-17F have been implicated in thepathogenesis of several immune-mediated inflammatory diseases including plaque psoriasis, psoriaticarthritis, axial spondyloarthritis and hidradenitis suppurativa. IL-17A and IL-17F cooperate and/orsynergise with other inflammatory cytokines to induce inflammation. IL17-F is produced in significantamount by innate immune cells. This production can be independent of IL-23. Bimekizumab inhibitsthe proinflammatory cytokines, resulting in the normalisation of skin inflammation and substantialdecrease of local and systemic inflammation, and as a consequence improvement in clinical signs andsymptoms associated with psoriasis, psoriatic arthritis, axial spondyloarthritis and hidradenitissuppurativa. From in vitro models, bimekizumab was shown to inhibit psoriasis-related geneexpression, cytokine production, the migration of inflammatory cells and pathological osteogenesis toa greater extent than inhibition of IL-17A alone.

Plaque psoriasis

The safety and efficacy of bimekizumab was evaluated in 1,480 patients with moderate to severeplaque psoriasis in three Phase 3 multicentre, randomised, placebo and/or active comparator-controlled studies. Patients were at least 18 years of age, had a Psoriasis Area and Severity Index(PASI) score ≥12 and Body Surface Area (BSA) affected by psoriasis (PSO) ≥10%, an Investigators

Global Assessment (IGA) score ≥3 on a 5-point scale and were candidates for systemic psoriasistherapy and/or phototherapy. The efficacy and safety of bimekizumab were evaluated versus placeboand ustekinumab (BE VIVID - PS0009), versus placebo (BE READY - PS0013) and versusadalimumab (BE SURE - PS0008).

The BE VIVID study evaluated 567 patients for 52 weeks where patients were randomised to receiveeither bimekizumab 320 mg every 4 weeks, ustekinumab (45 mg or 90 mg, depending on patientweight, at baseline and week 4 and then every 12 weeks), or placebo for an initial 16 weeks, followedby bimekizumab 320 mg every 4 weeks.

The BE READY study evaluated 435 patients for 56 weeks. Patients were randomised to receivebimekizumab 320 mg every 4 weeks or placebo. At week 16, patients who achieved a PASI 90response entered the 40-week randomised withdrawal period. Patients initially randomised tobimekizumab 320 mg every 4 weeks were re-randomised to either bimekizumab 320 mg every 4weeks or bimekizumab 320 mg every 8 weeks or placebo (i.e. withdrawal of bimekizumab). Patientsinitially randomised to placebo continued to receive placebo provided they were PASI 90 responders.

Patients who did not achieve a PASI 90 response at week 16 entered an open-label escape arm andreceived bimekizumab 320 mg every 4 weeks for 12 weeks. Patients who relapsed (did not achieve

PASI 75 response) during the randomised withdrawal period also entered the 12-week escape arm.

The BE SURE study evaluated 478 patients for 56 weeks. Patients were randomised to receive eitherbimekizumab 320 mg every 4 weeks through week 56, bimekizumab 320 mg every 4 weeks throughweek 16 followed by bimekizumab 320 mg every 8 weeks through week 56 or adalimumab as perlabelling recommendation through week 24 followed by bimekizumab 320 mg every 4 weeks throughweek 56.

Baseline characteristics were consistent across all 3 studies: patients were predominantly male(70.7%) and white (84.1%), with a mean age of 45.2 years (18 to 83 years), and 8.9% were ≥65 yearsof age. The median baseline BSA was 20%, the median baseline PASI score was 18 and the baseline

IGA score was severe in 33% of patients. The median baseline scores for Patient Symptoms Diary(PSD) pain, itch and scaling items ranged between 6 and 7 on a 0-10 points scale and the medianbaseline Dermatology Life Quality Index (DLQI) total score was 9.

Across all 3 studies, 38% of patients had received a prior biologic therapy; 23% had received at leastone anti-IL17 agent (primary anti-IL17 failures were excluded) and 13% had received at least one

TNF-antagonist. Twenty-two percent were naïve to any systemic therapy (including non-biologic andbiologic) and 39% of patients had received prior phototherapy or photochemotherapy.

The efficacy of bimekizumab was evaluated with respect to impact on skin disease overall, specificbody locations (scalp, nails, palms and soles), patient reported symptoms and impact on quality of life.

The two co-primary endpoints in all 3 studies were the proportion of patients who achieved 1) a PASI90 response and 2) an IGA “clear or almost clear” (IGA 0/1with at least two points improvement frombaseline) response at week 16. PASI 100, IGA 0 response at week 16 and PASI 75 response at week 4were secondary endpoints in all 3 studies.

Treatment with bimekizumab resulted in significant improvement across efficacy endpoints comparedto placebo, ustekinumab or adalimumab at week 16. The main efficacy results are shown in Table 2.

Table 2: Summary of clinical responses in BE VIVID, BE READY and BE SURE

BE VIVID BE READY BE SURE

Placebo Bimekizumab Ustekinumab Placebo Bimekizumab Bimekizumab Adalimumab320 mg Q4W 320 mg Q4W 320 mg Q4W(N= 83) (N= 321) (N=163) (N= 86) (N= 349) (N= 319) (N= 159)n (%) n (%) n (%) n (%) n (%) n (%) n (%)

PASI 100

Week 16 0 (0.0) 188 (58.6)a 34 (20.9) 1 (1.2) 238 (68.2)a 194 (60.8)a 38 (23.9)

PASI 90

Week 16 4 (4.8) 273 (85.0)a, b 81 (49.7) 1 (1.2) 317 (90.8)a 275 (86.2)a 75 (47.2)

PASI 75

Week 4 2 (2.4) 247 (76.9)a, b 25 (15.3) 1 (1.2) 265 (75.9)a 244 (76.5)a 50 (31.4)

Week 16 6 (7.2) 296 (92.2) 119 (73.0) 2 (2.3) 333 (95.4) 295 (92.5) 110 (69.2)

IGA 0

Week 16 0 (0.0) 188 (58.6)a 36 (22.1) 1 (1.2) 243 (69.6)a 197 (61.8) 39 (24.5)

IGA 0/1

Week 16 4 (4.8) 270 (84.1)a, b 87 (53.4) 1 (1.2) 323 (92.6)a 272 (85.3)a 91 (57.2)

Absolute

PASI ≤ 2

Week 16 3 (3.6) 273 (85.0) 84 (51.5) 1 (1.2) 315 (90.3) 280 (87.8) 86 (54.1)

PSD Pain (N=48) (N=190) (N=90) (N=49) (N=209) (N=222) (N=92)improvement≥4 (N)

Week 16 5 (10.4) 140 (73.7) 54 (60.0) 0 (0.0) 148 (70.8) 143 (64.4) 43 (46.7)

PSD Itch (N=53) (N=222) (N=104) (N=60) (N=244) (N=248) (N=107)improvement≥4 (N)

Week 16 6 (11.3) 151 (68.0) 57 (54.8) 0 (0.0) 161 (66.0) 153 (61.7) 42 (39.3)

PSD Scaling (N=56) (N=225) (N=104) (N=65) (N=262) (N=251) (N= 109)improvement≥4 (N)

Week 16 6 (10.7) 171 (76.0) 59 (56.7) 1 (1.5) 198 (75.6) 170 (67.7) 42 (38.5)

Bimekizumab 320 mg Q4W= bimekizumab every 4 weeks. Non-Responder Imputation (NRI) is used.

IGA 0/1 response was defined as Clear (0) or Almost Clear (1) with at least a 2-category improvement from Baseline atweek 16. IGA 0 response was defined as Clear (0) with at least a 2-category improvement from Baseline at week 16.

PSD is a Patient Symptoms Diary, also referred to as Psoriasis Symptoms and Impacts Measure (P-SIM), measuring psoriasissymptom severity on a scale from 0 (no symptoms) to 10 (very severe symptoms). Response is defined as a decrease ≥4 frombaseline to week 16 for pain, itch and scaling on a scale from 0 to 10.a) p<0.001 versus placebo (BE VIVID and BE READY), versus adalimumab (BE SURE), adjusted for multiplicity.b) p<0.001 versus ustekinumab (BE VIVID), adjusted for multiplicity.

Bimekizumab was associated with a rapid onset of efficacy. In BE VIVID, at week 2 and week 4,

PASI 90 response rates were significantly higher for bimekizumab-treated patients (12.1% and 43.6%respectively) compared to placebo (1.2% and 2.4% respectively) and ustekinumab (1.2% and 3.1%respectively).

In the BE VIVID study, at week 52, bimekizumab-treated patients (every 4 weeks) achievedsignificantly higher response rates than the ustekinumab-treated patients on the endpoints of PASI 90(81.9% bimekizumab vs 55.8% ustekinumab, p<0.001), IGA 0/1 (78.2% bimekizumab vs 60.7%ustekinumab, p<0.001) and PASI 100 (64.5% bimekizumab vs 38.0% ustekinumab).

Figure 1: PASI 90 responder rates over time in BE VIVID

BKZ 320 mg Q4W=bimekizumab every 4 weeks; Uste=ustekinumab. NRI is used.

In the BE SURE study at week 24, a significantly higher percentage of patients treated withbimekizumab (Q4W/Q4W and Q4W/Q8W combined dosing arms) achieved PASI 90 and IGA 0/1responses as compared with adalimumab (85.6% and 86.5% respectively vs 51.6% and 57.9%respectively, p<0.001). At week 56, 70.2% of patients treated with bimekizumab Q8W achieved a

PASI 100 response. Among the 65 adalimumab non-responders at week 24 (< PASI 90), 78.5%achieved a PASI 90 response after 16 weeks of treatment with bimekizumab. The safety profileobserved in patients who switched from adalimumab to bimekizumab without a wash-out period wassimilar to patients who initiated bimekizumab after wash-out of prior systemic therapies.

Figure 2: PASI 90 responder rates over time in BE SURE

BKZ 320 mg Q4W = bimekizumab every 4 weeks; BKZ 320 mg Q8W = bimekizumab every 8 weeks; ADA= adalimumab.

Patients in the BKZ Q4W/Q8W group switched from Q4W to Q8W dosing at week 16. Patients in the ADA/BKZ 320 mg

Q4W group switched from ADA to BKZ Q4W at week 24. NRI is used.

The efficacy of bimekizumab was demonstrated regardless of age, gender, race, disease duration, bodyweight, PASI baseline severity and previous treatment with a biologic. Bimekizumab was efficaciousin prior biologic exposed patients, including anti-TNF/anti IL-17 and in systemic treatment-naïvepatients. Efficacy in patients with primary failure to anti-IL17 has not been investigated.

Based on population PK/ PD analysis and supported by clinical data, patients with higher body weight(≥120 kg) who did not achieve complete skin clearance at week 16 benefited from continuedbimekizumab 320 mg every four weeks (Q4W) after the initial 16 weeks of treatment. In the BE

SURE study, patients received bimekizumab 320 mg Q4W through week 16, followed by either Q4Wor every eight weeks (Q8W) dosing through week 56, regardless of responder status at week 16.

Patients in the ≥120 kg group (N=37) on the Q4W maintenance regimen showed greater improvementin PASI 100 between week 16 (23.5%) and week 56 (70.6%) compared to those on the Q8Wmaintenance regimen (week 16: 45.0% vs week 56: 60.0%).

Improvements were observed in psoriasis involving the scalp, nails, palms and soles in patients treatedwith bimekizumab at week 16 (see Table 3).

Table 3: Scalp, palmoplantar and nail responses in BE VIVID, BE READY and BE SURE atweek 16

BE VIVID BE READY BE SURE

Placebo Bimekizumab Ustekinumab Placebo Bimekizumab Bimekizumab Adalimumab320 mg Q4W 320 mg Q4W 320 mg Q4W

Scalp IGA(N)a (72) (285) (146) (74) (310) (296) (138)

Scalp IGA0/1, n (%) 11 (15.3) 240 (84.2)b 103 (70.5) 5 (6.8) 286 (92.3)b 256 (86.5) 93 (67.4)pp-IGA(N)a (29) (105) (47) (31) (97) (90) (34)pp-IGA 0/1,n (%) 7 (24.1) 85 (81.0) 39 (83.0) 10 (32.3) 91 (93.8) 75 (83.3) 24 (70.6)mNAPSI100 (N)a (51) (194) (109) (50) (210) (181) (95)mNAPSI100, n (%) 4 (7.8) 57 (29.4) 15 (13.8) 3 (6.0) 73 (34.8) 54 (29.8) 21 (22.1)

Bimekizumab 320 mg Q4W= bimekizumab every 4 weeks. Non responder imputation (NRI) is used.

Scalp IGA 0/1 and pp-IGA 0/1 responses were defined as Clear (0) or Almost Clear (1) with ≥2 category improvementrelative to Baseline.a) Include only patients with a scalp Investigator Global Assessment (IGA) of 2 or greater, a palmoplantar IGA of 2 or greaterand a modified Nail Psoriasis and Severity Index (mNAPSI) score > 0 at baseline.b) p<0.001 versus placebo, adjusted for multiplicity

Scalp IGA and palmoplantar IGA responses in bimekizumab-treated patients were maintained throughweek 52/56. Nail psoriasis continued to improve beyond week 16. In BE VIVID, at week 52, 60.3%of patients treated with bimekizumab 320 mg every 4 weeks achieved complete nail clearance(mNAPSI 100). In BE READY, at week 56, 67.7% and 69.8% of week 16 PASI 90 respondersachieved complete nail clearance with bimekizumab 320 mg every 8 weeks and bimekizumab 320 mgevery 4 weeks respectively.

Table 4: Maintenance of responses with bimekizumab at week 52 in PASI 100, PASI 90, IGA 0/1and Absolute PASI ≤ 2 responders at week 16*

PASI 100 PASI 90 IGA 0/1 Absolute PASI ≤ 2320 mg 320 mg 320 mg 320 mg 320 mg 320 mg 320 mg 320 mg

Q4W Q8W Q4W Q8W Q4W Q8W Q4W Q8W(N=355) (N=182) (N=516) (N=237) (N=511) (N=234) (N=511) (N= 238)n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%)295 (83.1) 161 (88.5) 464 (89.9) 214 (90.3) 447 (87.5) 214 (91.5) 460 (90.0) 215 (90.3)

* Integrated analysis of BE VIVID, BE READY and BE SURE. NRI is used.320 mg Q4W: bimekizumab 320 mg every 4 weeks followed by bimekizumab 320 mg every 4 weeks from week 16.320 mg Q8W: bimekizumab 320 mg every 4 weeks followed by bimekizumab 320 mg every 8 weeks from week 16.

Figure 3: PASI 90 responder rates over time for PASI 90 responders at week 16 - Randomisedwithdrawal period in BE READY

NRI is used.

At week 16, 105 study participants started the Randomised-Withdrawal Period in the bimekizumab 320 mg Q4W/placebogroup, 100 in the bimekizumab 320 mg Q4W/Q8W group, and 106 in the bimekizumab 320 mg Q4W/Q4W group.

In BE READY, for PASI 90 responders at week 16 who were re-randomised to placebo andwithdrawn from bimekizumab, the median time to relapse, defined as loss of PASI 75, wasapproximately 28 weeks (32 weeks after the last bimekizumab dose). Among these patients, 88.1%regained a PASI 90 response within 12 weeks of restarting treatment with bimekizumab 320 mg every4 weeks.

Health-related Quality of Life/Patient reported outcomes

Across all 3 studies, a greater proportion of patients treated with bimekizumab experienced no impactof psoriasis on their quality of life as measured by the Dermatology Life Quality Index (DLQI)compared to placebo and active comparator-treated patients at week 16 (Table 5).

Table 5: Quality of life in study BE VIVID, BE READY and BE SURE

BE VIVID BE READY BE SURE

Placebo Bimekizumab Ustekinumab Placebo Bimekizumab Bimekizumab Adalimumab320 mg Q4W 320 mg Q4W 320 mg Q4W(N= 83) (N= 321) (N= 163) (N= 86) (N= 349) (N= 319) (N= 159)n (%) n (%) n (%) n (%) n (%) n (%) n (%)

DLQI 0/1a

Baseline 3 (3.6) 16 (5.0) 5 (3.1) 4 (4.7) 11 (3.2) 10 (3.1) 13 (8.2)

DLQI 0/1a

Week 16 10 (12.0) 216 (67.3) 69 (42.3) 5 (5.8) 264 (75.6) 201 (63.0) 74 (46.5)a) DLQI absolute score of 0 or 1 indicates no impact of the disease on health-related quality of life. NRI is used.

DLQI 0/1 responses continued to increase beyond week 16 and then were maintained through week52/56. In BE VIVID, DLQI 0/1 response rate at week 52 was 74.8% in patients treated withbimekizumab 320 mg every 4 weeks. In BE SURE at week 56, 78.9% and 74.1% of patients had a

DLQI 0/1 with bimekizumab 320 mg every 8 weeks and bimekizumab 320 mg every 4 weeks,respectively.

Phase 3 Open Label Extension study

Patients who completed one of the pivotal phase 3 studies (‘feeder studies’) could enter a 144-weekopen-label extension study (PS0014) to assess the long-term safety and efficacy of bimekizumab.

344 patients who were treated with bimekizumab 320 mg every 8 weeks (BKZ 320 mg Q8W) or every4 weeks (BKZ 320 mg Q4W) during the feeder study, and who achieved PASI 90 at the end of thefeeder study, received bimekizumab 320 mg Q8W throughout PS0014. Of these, 293 (85.2%) patientscompleted 144 weeks of treatment with bimekizumab 320 mg Q8W. 48 patients (14.0%) discontinuedthe study during the treatment period, of which 21 (6.1%) discontinued due to an adverse event and 4(1.2%) discontinued due to lack of efficacy.

Among the patients remaining in the study, improvements achieved with bimekizumab for the efficacyendpoints PASI 90 and IGA 0/1 in the feeder studies were maintained through an additional 144weeks of open-label treatment.

Phase 3b direct comparative study versus secukinumab

The efficacy and safety of bimekizumab were also evaluated in a double-blind study compared withsecukinumab, an IL-17A inhibitor, (BE RADIANT - PS0015). Patients were randomised to receivebimekizumab (N=373, 320 mg at week 0, 4, 8, 12 and 16 (Q4W) followed by 320 mg every 4 weeks(Q4W/Q4W) or 320 mg every 8 weeks (Q4W/Q8W)) or secukinumab (N=370, 300 mg at weeks 0,1,2, 3, 4 followed by 300 mg every 4 weeks). Baseline characteristics were consistent with a populationof moderate to severe plaque psoriasis patients with a median BSA of 19% and a median PASI scoreof 18.

Bimekizumab-treated patients achieved significantly higher response rates compared to secukinumabfor the primary endpoint of PASI 100 (complete skin clearance) at week 16. Significantly higherresponse rates were also achieved with bimekizumab for the secondary endpoint of PASI 100 at week48 (for both Q4W/Q4W and Q4W/Q8W regimens). Comparative PASI response rates are presented in

Table 6.

Differences in response rates between bimekizumab and secukinumab-treated patients were noted asearly as week 1 for PASI 75 (7.2% and 1.4% respectively) and as early as week 2 for PASI 90 (7.5%and 2.4% respectively).

Table 6: PASI response rates from BE RADIANT - bimekizumab versus secukinumab

Week 4 Week 16 Week 48a)

Bimekizumab Secukinumab Bimekizumab Secukinumab Bimekizumab Bimekizumab Secukinumab320 mg Q4W 320 mg Q4W 320 mg 320 mg

Q4W/Q4W Q4W/Q8W(N=373) (N=370) (N=373) (N=370) (N=147) (N=215) (N=354)n (%) n (%) n (%) n (%) n (%) n (%) n (%)

PASI 100 52 (13.9) 23 (6.2) 230 (61.7)* 181 (48.9) 108 (73.5)* 142 (66.0)* 171 (48.3)

PASI 90 134 (35.9) 65 (17.6) 319 (85.5) 275 (74.3) 126 (85.7) 186 (86.5) 261 (73.7)

PASI 75 265 (71.0)* 175 (47.3) 348 (93.3) 337 (91.1) 134 (91.2) 196 (91.2) 301 (85.0)

Absolute 151 (40.5) 75 (20.3) 318 (85.3) 283 (76.5) 127 (86.4) 186 (86.5) 269 (76.0)

PASI<2a) Data are from the Maintenance Set consisting of patients who received at least one dose of study treatment at week 16 orlater

*p<0.001 versus secukinumab, adjusted for multiplicity. NRI is used.

Bimekizumab and secukinumab PASI 100 response rates through week 48 are presented in Figure 4.

Figure 4: PASI 100 response rate over time in BE RADIANT

NRI is used. Maintenance Set consisting of patients who received at least one dose of study treatment at week 16 or later

The efficacy of bimekizumab in BE RADIANT was consistent with BE VIVID, BE READY and BE

SURE.

Phase 3b Open Label Extension period

At week 48, patients were allowed to enter a 96-week open-label extension period (OLE) and startedor continued with bimekizumab 320 mg Q4W or 320 mg Q8W depending on their PASI 90 responderstatus at week 48. Study participants who initially received bimekizumab 320 mg Q4W during the

OLE were switched to bimekizumab 320 mg Q8W at week 72 or later.

231 patients who were treated with bimekizumab 320 mg Q8W or bimekizumab 320 mg Q4W andachieved PASI 90 at week 48 received bimekizumab 320 mg Q8W throughout the OLE. Of thesepatients, 31 (13.4%) discontinued the study during the OLE, of which 10 (4.3%) discontinued due toan adverse event and 1 (0.4%) discontinued due to lack of efficacy.

116 patients who were treated with secukinumab and achieved PASI 90 at week 48 receivedbimekizumab 320 mg Q8W throughout the OLE. Of these patients, 16 (13.8%) discontinued the studyduring the OLE, of which 6 (5.2%) discontinued due to an adverse event and 1 (0.9%) discontinueddue to lack of efficacy.

Among the patients remaining in the study, improvements achieved with bimekizumab orsecukinumab for the efficacy endpoints PASI 100, PASI 90, PASI 75 and PASI ≤2 responder at week48 were maintained on treatment with bimekizumab 320 mg Q8W through an additional 96 weeks ofopen-label treatment.

The safety profile of bimekizumab up to week 144 was consistent with the safety profile observed upto 48 weeks.

Psoriatic arthritis (PsA)

The safety and efficacy of bimekizumab were evaluated in 1112 adult patients (at least 18 years ofage) with active psoriatic arthritis (PsA) in two multicentre, randomised, double-blind, placebo-controlled studies (PA0010 - BE OPTIMAL and PA0011- BE COMPLETE). The BE OPTIMALstudy included an active reference treatment arm (adalimumab) (N=140).

For both studies, patients had a diagnosis of active psoriatic arthritis for at least 6 months based on the

Classification Criteria for Psoriatic Arthritis (CASPAR) and had active disease with tender joint count(TJC) ≥3 and swollen joint count (SJC) ≥3. Patients had a diagnosis of PsA for a median of 3.6 yearsin BE OPTIMAL and 6.8 years in BE COMPLETE. Patients with each subtype of PsA were enrolledin these studies, including polyarticular symmetric arthritis, oligoarticular asymmetric arthritis, distalinterphalangeal joint predominant, spondylitis predominant and arthritis mutilans. At baseline, 55.9%of patients had ≥ 3% Body Surface Area (BSA) with active plaque psoriasis. 10.4% of patients hadmoderate to severe plaque psoriasis and 31.9% and 12.3% had enthesitis and dactylitis at baseline,respectively. The primary efficacy endpoint in both studies was the American College of

Rheumatology (ACR) 50 response at week 16.

The BE OPTIMAL study evaluated 852 patients not previously exposed to any biologic disease-modifying anti-rheumatic drug (bDMARD) for the treatment of psoriatic arthritis or psoriasis. Patientswere randomised (3:2:1) to receive bimekizumab 160 mg every 4 weeks through week 52 or placeboup to week 16 followed by bimekizumab 160 mg every 4 weeks through week 52 or an activereference treatment arm (adalimumab 40 mg every 2 weeks) up to week 52. In this study, 78.3% ofpatients had received prior treatment with ≥ 1 cDMARDs and 21.7 % of patients had no priortreatment with cDMARDs. At baseline, 58.2% of patients were receiving concomitant methotrexate(MTX), 11.3% were receiving concomitant cDMARDs other than MTX, and 30.5% were receiving nocDMARDs.

The BE COMPLETE study evaluated 400 patients with an inadequate response (lack of efficacy) orintolerance to treatment with 1 or 2 tumour necrosis factor alpha inhibitors (anti-TNFα - IR) for eitherpsoriatic arthritis or psoriasis. Patients were randomised (2:1) to receive bimekizumab 160 mg every 4weeks or placebo up to week 16. At baseline, 42.5% of patients were receiving concomitant MTX,8.0% were receiving concomitant cDMARDs other than MTX, and 49.5% were receiving nocDMARDs. In this study, 76.5% of participants had an inadequate response to 1 TNFα inhibitor,11.3% had an inadequate response to 2 TNFα inhibitors and 12.3% were intolerant to TNFα inhibitors.

Signs and symptoms

In bDMARDs-naïve patients (BE OPTIMAL) and anti-TNFα IR patients (BE COMPLETE) treatmentwith bimekizumab resulted in significant improvement in signs and symptoms and measures ofdisease activity compared to placebo at week 16, with similar response rates seen in both patientpopulations (see Table 7). Clinical responses were sustained up to week 52 in BE OPTIMAL asassessed by ACR 20, ACR 50, ACR 70, MDA, PASI 90, PASI 100 and ACR 50/PASI 100.

Table 7: Clinical response in study BE OPTIMAL and BE COMPLETE

BE OPTIMAL (bDMARD-naïve) BE COMPLETE (anti TNFα-IR)

Placebo BKZ 160 mg Difference Reference Placebo BKZ 160 mg Difference(e)(N=281) Q4W from placebo Arm(Adalimumab) (N=133) Q4W from placebon (%) (N=431) (95% CI)(d) (N=140)e n (%) (N=267) (95% CI)(d)n (%) n (%) n (%)

ACR 20

Week 16 67 (23.8) 268 (62.2) 38.3 (31.4, 45.3) 96 (68.6) 21 (15.8) 179 (67.0) 51.2 (42.1, 60.4)

Week 24 - 282 (65.4) 99 (70.7)

Week 52 307 (71.2) 102 (72.9)

ACR 50

Week 16 28 (10.0) 189 (43.9)* 33.9 (27.4, 40.4) 64 (45.7) 9 (6.8) 116 (43.4)* 36.7 (27.7, 45.7)

Week 24 - 196 (45.5) 66 (47.1)

Week 52 235 (54.5) 70 (50.0)

ACR 70

Week16 12 (4.3) 105 (24.4) 20.1 (14.7, 25.5) 39 (27.9) 1 (0.8) 71 (26.6) 25.8 (18.2, 33.5)

Week 24 - 126 (29.2) 42 (30.0)

Week 52 169 (39.2) 53 (37.9)

MDA(a)

Week 16 37 (13.2) 194 (45.0)* 31.8 (25.2, 38.5) 63 (45.0) 8 (6.0) 118 (44.2)* 38.2 (29.2, 47.2)

Week 24 - 209 (48.5) 67 (47.9)

Week 52 237 (55.0) 74 (52.9)

Patients with(N=140) (N=217) (N=68) (N=88) (N=176)≥3% BSA

PASI 90

Week 16 4 (2.9) 133 (61.3)* 58.4 (49.9, 66.9) 28 (41.2) 6 (6.8) 121 (68.8)* 61.9 (51.5, 72.4)

Week 24 - 158 (72.8) 32 (47.1)

Week 52 155 (71.4) 41 (60.3)

PASI 100

Week 16 3 (2.1) 103 (47.5) 45.3 (36.7, 54.0) 14 (20.6) 4 (4.5) 103 (58.5) 54.0 (43.1, 64.8)

Week 24 - 122 (56.2) 26 (38.2)

Week 52 132 (60.8) 33 (48.5)

ACR50/

PASI 100

Week 16 0 60 (27.6) NC (NC, NC) 11 (16.2) 1 (1.1) 59 (33.5) 32.4 (22.3, 42.5)

Week 24 - 68 (31.3) 17 (25.0)

Week 52 102 (47.0) 24 (35.3)

Patients with(N=47) (N=90)

LDI>0 (b)

Dactylitisfree state (b)

Week 16 24 (51.1) 68 (75.6)*** 24.5 (8.4, 40.6)

Patientswith LEI>0 (N=106) (N=249)(c)

Enthesitisfree state (c)

Week 16 37 (34.9) 124 (49.8)** 14.9 (3.7, 26.1)

ACR50/PASI 100= composite ACR50 and PASI 100 response. BKZ 160 mg Q4W= bimekizumab 160 mg every 4 weeks.

CI= confidence interval. NC=Not calculable(a) A patient was classified as achieving Minimal Disease Activity (MDA) when meeting 5 of the 7 following criteria: tenderjoint count ⩽1; swollen joint count ⩽1; Psoriasis Activity and Severity Index ⩽1 or body surface area ⩽3; patient pain visualanalogue scale (VAS) ⩽15; patient global disease activity VAS ⩽20; Health Assessment Questionnaire Disability Index⩽0.5; tender entheseal points ⩽1(b) Based on pooled data from BE OPTIMAL and BE COMPLETE studies for patients with baseline Leeds Dactylitis Index(LDI) >0. Dactylitis free state is LDI=0(c) Based on pooled data from BE OPTIMAL and BE COMPLETE studies for patients with baseline Leeds Enthesitis Index(LEI) >0. Enthesitis free state is LEI =0(d) Unadjusted differences are shown(e) No statistical comparison to bimekizumab or placebo performed

* p<0.001 versus placebo adjusted for multiplicity. ** p=0.008 versus placebo adjusted for multiplicity. *** p=0.002 versusplacebo adjusted for multiplicity. NRI is used. Other endpoints at week 16 and all endpoints at week 24 and week 52 werenot part of the sequential testing hierarchy and any comparisons are nominal.

Improvements from baseline were shown in all individual ACR components with bimekizumab atweek 16 and were sustained up to week 52 in BE OPTIMAL.

Treatment responses on bimekizumab were significantly greater than those on placebo as early asweek 2 for ACR 20 (BE OPTIMAL, 27.1% versus 7.8%, nominal p<0.001) and week 4 for ACR 50(BE OPTIMAL, 17.6% versus 3.2%, nominal p<0.001 and BE COMPLETE, 16.1% versus 1.5%,nominal p<0.001).

Figure 5: ACR 50 response over time up to week 52 in BE OPTIMAL (NRI)

Patients on placebo switched to bimekizumab 160 mg Q4W at week 16.

Figure 6: ACR 50 response over time up to week 16 in BE COMPLETE (NRI)

For the bimekizumab-treated patients who achieved an ACR 50 response at week 16 in BE

OPTIMAL, 87.2% maintained this response at week 52.

The efficacy and safety of bimekizumab were demonstrated regardless of age, gender, race, baselinebody weight, baseline psoriasis involvement, baseline CRP, disease duration and prior cDMARDs use.

In both studies, similar responses were observed with bimekizumab regardless of whether patientswere on concomitant cDMARDs, including MTX, or not.

The modified Psoriatic Arthritis Response Criteria (PsARC) is a specific composite responder indexcomprising of tender joint count, swollen joints count, patient and physician global assessment. Theproportion of patients achieving modified PsARC at week 16 was higher in the bimekizumab-treatedpatients compared to placebo (80.3% versus 40.2% respectively in BE OPTIMAL and 85.4% versus30.8% respectively in BE COMPLETE). PsARC response was sustained up to week 52 in BE

OPTIMAL.

In BE OPTIMAL, inhibition of progression of structural damage was assessed radiographically andexpressed as the change from baseline in the Van der Heijde modified total Sharp Score (vdHmTSS)and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at week 16(see Table 8).

Table 8: Change in vdHmTSS in BE OPTIMAL at week 16

Placebo BKZ 160mg Q4W Difference fromplacebo (95% CI)a)

Population with elevated hs-CRP and/or at(N=227) (N=361)least 1 bone erosion at baseline

Mean change from baseline (SE) 0.36 (0.10) 0.04 (0.05)* -0.32 ( -0.35, -0.30)

Overall population (N=269) (N=420)

Mean change from baseline (SE) 0.32 (0.09) 0.04 (0.04)* -0.26 ( -0.29, -0.23)

*p =0.001 versus placebo. p-values are based on reference-based imputation using difference in LS Mean using an ANCOVAmodel with treatment, bone erosion at Baseline and region as fixed effects and Baseline score as a covariate.

Week 16 summary data is based on the first set of reads for the primary analysis.a) Unadjusted differences are shown

Bimekizumab significantly inhibited the progression of joint damage at week 16 in both the populationwith elevated hs-CRP and/or at least 1 bone erosion at baseline and the overall population compared toplacebo. While reference-based imputation was specified as the missing data handling method in thestatistical testing procedure comparing bimekizumab versus placebo, changes from baseline were alsocalculated using standard multiple imputation in both the population with elevated hs-CRP and/or atleast 1 bone erosion at baseline and the overall population at week 16 in the bimekizumab arm (meanchange from baseline 0.01 and 0.01 respectively) and the adalimumab arm (mean change frombaseline -0.05 and -0.03 respectively). Inhibition of the progression of joint damage was sustained inboth the population with elevated hs-CRP and/or at least 1 bone erosion at baseline and the overallpopulation to week 52 in both the bimekizumab arm (mean change from baseline 0.10 and 0.10respectively) and the adalimumab arm (mean change from baseline -0.17 and -0.12 respectively).

The observed percentage of patients with no radiographic joint damage progression (defined as achange from baseline in mTSS of ≤0.5) from randomisation to week 52 was 87.9% (N=276/314) forbimekizumab and 84.8% (N=168/198) for placebo study participants switching to bimekizumab and94.1% (N=96/102) for adalimumab in the population with elevated hs-CRP and/or at least 1 boneerosion. Similar rates were observed in the overall population (89.3% (N=326/365) for bimekizumaband 87.3% (N=207/237) for placebo study participants switching to bimekizumab and 94.1%(N=111/118) for adalimumab).

Physical function and other health-related outcomes

Both bDMARD-naïve (BE OPTIMAL) and anti-TNFα-IR (BE COMPLETE) patients receivingbimekizumab showed significant improvement from baseline in physical function compared toplacebo patients at week 16 (p<0.001) as assessed by the HAQ-DI (LS Mean change from baseline:

- 0.3 versus - 0.1 in BE OPTIMAL and - 0.3 versus 0 in BE COMPLETE, respectively). In bothstudies, a greater proportion of patients achieved a clinically meaningful reduction of at least 0.35 in

HAQ-DI score from baseline in the bimekizumab group compared with placebo at week 16.

Bimekizumab-treated patients reported significant improvement from baseline in the Short Form-36item Health Survey Physical Component Summary (SF-36 PCS) score at week 16 compared toplacebo (LS Mean change from baseline: 6.3 versus 1.9, p<0.001 in BE OPTIMAL and 6.2 versus 0.1,p<0.001 in BE COMPLETE).

In both studies, bimekizumab-treated patients reported meaningful reduction from baseline in fatigueas measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at week16 compared to placebo. Meaningful improvement from baseline was also observed in the Psoriatic

Arthritis Impact of Disease-12 (PsAID-12) score in the bimekizumab-treated group compared to theplacebo group at week 16.

Patients with axial involvement at baseline, approximately 74% of patients, (defined as a Bath

Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4) showed greater improvementfrom baseline in BASDAI compared with placebo at week 16.

Improvements achieved at week 16 in all measures of physical function and other health-relatedoutcomes mentioned above (HAQ-DI, SF-36 PCS, FACIT-Fatigue, PsAID-12 scores and BASDAI)were sustained up to week 52 in BE OPTIMAL.

In BE OPTIMAL, at week 52, 65.5% of patients treated with bimekizumab achieved complete nailclearance (mNAPSI resolution in patients with mNAPSI higher than 0 at Baseline).

Axial spondyloarthritis (nr-axSpA and AS)

The efficacy and safety of bimekizumab was evaluated in 586 adult patients (at least 18 years of age)with active axial spondyloarthritis (axSpA) in two multicentre, randomised, double-blind, placebo-controlled studies, one in non-radiographic axial spondyloarthritis (nr-axSpA) and one in ankylosingspondylitis (AS), also known as radiographic axSpA. The primary endpoint in both studies was thepercentage of patients achieving an Assessment of SpondyloArthritis International Society (ASAS) 40response at week 16. Consistent results were seen across both patient populations.

The BE MOBILE 1 study (AS0010) evaluated 254 patients with active nr-axSpA. Patients had axSpA(age of symptoms onset < 45 years) meeting the ASAS classification criteria and had active disease asdefined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and spinal pain ≥4 ona 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2) and no evidence of radiographic changesin the sacroiliac joints that would meet the modified New York criteria for AS. Patients also hadobjective signs of inflammation as indicated by elevated C-reactive protein (CRP) level and/orevidence of sacroiliitis on Magnetic Resonance Imaging (MRI) as well as a history of inadequateresponse to 2 different non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance orcontraindication to NSAIDs. Patients were randomised (1:1) to receive bimekizumab 160 mg every 4weeks up to week 52 or placebo up to week 16 followed by bimekizumab 160 mg every 4 weeks up toweek 52. At baseline, patients had symptoms of nr-axSpA for a mean of 9 years (median of 5.5 years).10.6% of patients were previously treated with an anti-TNFα agent.

The BE MOBILE 2 study (AS0011) evaluated 332 patients with active AS determined by documentedradiologic evidence (x-ray) fulfilling the Modified New York criteria for AS. Patients had activedisease as defined by a BASDAI ≥4 and spinal pain ≥4 on a 0 to 10 numeric rating scale (NRS) (from

BASDAI Item 2). Patients had to have a history of inadequate response to 2 different NSAIDs orintolerance or contraindication to NSAIDs. Patients were randomised (2:1) to receive bimekizumab160 mg every 4 weeks up to week 52 or placebo up to week 16 followed by bimekizumab 160 mgevery 4 weeks up to week 52. At baseline, patients had symptoms of AS for a mean of 13.5 years(median of 11 years). 16.3% of patients were previously treated with an anti-TNFα agent.

Treatment with bimekizumab resulted in significant improvement in signs and symptoms andmeasures of disease activity compared to placebo at week 16 in both nr-axSpA and AS patientpopulations (see Table 9). Clinical responses were sustained up to week 52 in both patient populationsas assessed by all the endpoints presented in Table 9.

Table 9: Clinical responses in BE MOBILE 1 and BE MOBILE 2

BE MOBILE 1 (nr-axSpA) BE MOBILE 2 (AS)

Placebo BKZ 160 mg Q4W Difference from Placebo BKZ 160 mg Q4W Difference froma) a)(N=126) (N=128) placebo (95% CI) (N=111) (N=221) placebo (95% CI)n (%) n (%) n (%) n (%)

ASAS 40

Week 16 27 (21.4) 61 (47.7)* 26.2 (14.9, 37.5) 25 (22.5) 99 (44.8)* 22.3 (11.5, 33.0)

Week 52 78 (60.9) 129 (58.4)

ASAS 40 in anti-TNFαnaives (N=109) (N= 118) (N=94) (N=184)

Week 16 25 (22.9) 55 (46.6) 24.8 (12.4, 37.1) 22 (23.4) 84 (45.7)* 22.3 (10.5, 34.0)

Week 52 73 (61.9) 108 (58.7)

ASAS 20

Week 16 48 (38.1) 88 (68.8)* 30.7 (19.0, 42.3) 48 (43.2) 146 (66.1)* 22.8 (11.8, 33.8)

Week 52 94 (73.4) 158 (71.5)

ASAS-partial remission

Week 16 9 (7.1) 33 (25.8)* 18.6 (9.7, 27.6) 8 (7.2) 53 (24.0)* 16.8 (8.1, 25.5)

Week 52 38 (29.7) 66 (29.9)

ASDAS-majorimprovement

Week 16 9 (7.1) 35 (27.3)* 20.2 (11.2, 29.3) 6 (5.4) 57 (25.8)* 20.4 (11.7, 29.1)

Week 52 47 (36.7) 71 (32.1)

BASDAI-50

Week 16 27 (21.4) 60 (46.9) 25.3 (14.0, 36.6) 29 (26.1) 103 (46.6) 20.5 (9.6, 31.4)

Week 52 69 (53.9) 119 (53.8)

BKZ 160 mg Q4W = bimekizumab 160 mg every 4 weeks. ASDAS = Ankylosing Spondylitis Disease Activity Score.

NRI is used.a) Unadjusted differences are shown.

*p<0.001 versus placebo, adjusted for multiplicity.

The proportion of patients in BE MOBILE 1 reaching ASDAS <2.1 (combining ASDAS-inactivedisease (ID) and ASDAS-low disease (LD)) at week 16 was 46.1% in the bimekizumab group versus21.1% in the placebo group (multiple imputation). At week 52, 61.6% of patients in the bimekizumabgroup achieved an ASDAS <2.1, including 25.2% in inactive disease state (ASDAS <1.3).

The proportion of patients in BE MOBILE 2 reaching ASDAS <2.1 (combining ASDAS-ID and

ASDAS-LD) at week 16 was 44.8% in the bimekizumab group versus 17.4% in placebo group(multiple imputation). At week 52, 57.1% of patients in the bimekizumab group achieved an ASDAS<2.1, including 23.4 % in inactive disease state (ASDAS <1.3).

All four ASAS 40 components (total spinal pain, morning stiffness, Bath Ankylosing Spondylitis

Functional Index [BASFI] and Patient’s Global Assessment of Disease Activity [PGADA]) wereimproved with bimekizumab treatment and contributed to the overall ASAS 40 response at week 16,and these improvements were sustained up to week 52 in both patient populations.

Improvements in other measures of efficacy are shown in Table 10.

Table 10: Other measures of efficacy in BE MOBILE 1 and BE MOBILE 2

BE MOBILE 1 (nr-axSpA) BE MOBILE 2 (AS)

Placebo BKZ 160 mg Q4W Placebo BKZ 160 mg Q4W(N= 126) (N= 128) (N= 111) (N=221)

Nocturnal spinal pain

Baseline 6.7 6.9 6.8 6.6

Mean change from baseline at Week 16 -1.7 -3.6* -1.9 -3.3*

Mean change from baseline at Week 52 -4.3 -4.1

BASDAI

Baseline 6.7 6.9 6.5 6.5

Mean change from baseline at Week 16 -1.5 -3.1* -1.9 -2.9*

Mean change from baseline at Week 52 -3.9 -3.6

BASMI

Baseline 3.0 2.9 3.8 3.9

Mean change from baseline at Week 16 -0.1 -0.4 -0.2 -0.5**

Mean change from baseline at Week 52 -0.6 -0.7hs-CRP (mg/L)

Baseline (Geometric Mean) 5.0 4.6 6.7 6.5

Ratio to baseline at Week 16 0.8 0.4 0.9 0.4

Ratio to baseline at Week 52 0.4 0.3

BASMI = Bath Ankylosing Spondylitis Metrology Index. Hs-CRP = high sensitivity C-reactive protein

MI is used.

*p<0.001 reference-based imputation, versus placebo, adjusted for multiplicity. **p<0.01 reference-based imputation, versusplacebo, adjusted for multiplicity.

Bimekizumab was associated with a rapid onset of efficacy in both nr-axSpA and AS patientpopulation.

Treatment responses on bimekizumab-treated patients for ASAS 40 were greater than those onplacebo as early as week 1 in BE MOBILE 1 (16.4% vs. 1.6%, nominal p<0.001) and week 2 in BE

MOBILE 2 (16.7% vs. 7.2%, nominal p=0.019).

Bimekizumab was also associated with a rapid decrease in systemic inflammation as measured by hs-

CRP levels as early as week 2 in both nr-axSpA and AS patient populations, with nominal p-values<0.001 in both studies.

Figure 7: ASAS 40 response over time up to week 52 in BE MOBILE 1 (NRI)

Patients on placebo switched to bimekizumab 160 mg Q4W at week 16

Figure 8: ASAS 40 response over time up to week 52 in BE MOBILE 2 (NRI)

Patients on placebo switched to Bimekizumab 160 mg Q4W at week 16

In an integrated analysis of BE MOBILE 1 and BE MOBILE 2, of bimekizumab-treated patients whoachieved an ASAS 40 response at week 16, 82.1% maintained this response at week 52.

The efficacy of bimekizumab was demonstrated regardless of age, gender, race, disease duration,baseline inflammation status, baseline ASDAS and concomitant cDMARDs.

Similar response in ASAS 40 was seen in patients regardless of prior anti-TNFα exposure.

At week 16, among patients with enthesitis at baseline, the proportion of patients (NRI) with enthesitisresolution as assessed by the Maastricht Ankylosing Spondylitis Enthesitis (MASES) index wasgreater with bimekizumab compared to placebo (BE MOBILE 1: 51.1% versus 23.9% and BE

MOBILE 2: 51.5% versus 32.8%). The resolution of enthesitis with bimekizumab was sustained up toweek 52 in both studies (BE MOBILE 1: 54.3% and BE MOBILE 2: 50.8%).

Reduction of inflammation

Bimekizumab reduced inflammation as measured by hs-CRP (see Table 10) and as assessed by MRIin an imaging sub-study. Signs of inflammation were assessed by MRI at baseline and week 16 andexpressed as change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC)score for sacroiliac joints and Ankylosing Spondylitis spine Magnetic Resonance Imagine-activity(ASspiMRI-a score in the Berlin modification) for the spine. Reduction of inflammatory signs in bothsacroiliac joints and the spine was observed in patients treated with bimekizumab as compared withplacebo (see Table 11). Reduction of inflammation as measured by hs-CRP and as assessed by MRIwas sustained to week 52.

Table 11: Reduction of inflammation as assessed by MRI in BE MOBILE 1 and BE MOBILE 2

BE MOBILE 1 (nr-axSpA) BE MOBILE 2 (AS)

Placebo BKZ 160 mg Q4W Placebo BKZ 160 mg Q4W

SPARCC score

Mean change from baseline a) at week 16 -1.56 -6.15 0.59 -4.51(N=62) (N=78) (N=46) (N=81)

Mean change from baseline a) at week 52 -7.57 -4.67(N=67) (N=78)

ASspiMRI-a (Berlin modifications) score

Mean change from baseline a) at week 16 0.03 -0.36 -0.34 -2.23(N=60) (N=74) (N=46) (N=81)

Mean change from baseline a) at week 52 -0.70 -2.38(N=65) (N=77)a) Change from baseline values are based on observed cases as assessed by central read of week 52 dataset.

Physical function and other health-related outcomes

Patients treated with bimekizumab showed significant improvement from baseline in physical functionas assessed by the BASFI compared to placebo (LS Mean change from baseline at week 16 in BE

MOBILE 1: -2.4 versus -0.9, p<0.001 and in BE MOBILE 2: -2.0 versus -1.0, p<0.001). Patientstreated with bimekizumab reported significant improvement from baseline compared to placebo-treated patients in SF-36 PCS score (LS Mean change from baseline at week 16 in BE MOBILE 1: 9.3versus 5.4, p<0.001 and in BE MOBILE 2: 8.5 versus 5.2, p<0.001).

Patients treated with bimekizumab reported significant improvement from baseline in health-relatedquality of life as measured by the AS Quality of Life Questionnaire (ASQoL) compared to placebo(LS Mean change from baseline at week 16 in BE MOBILE 1: -4.9 versus -2.3, p<0.001 and in BE

MOBILE 2: -4.6 versus -3.0, p<0.001) as well as meaningful reduction in fatigue as assessed by the

FACIT-Fatigue score (Mean change from baseline at Week 16 in BE MOBILE 1: 8.5 forbimekizumab versus 3.9 for placebo and in BE MOBILE 2: 8.4 for bimekizumab versus 5.0 forplacebo).

Improvements achieved at week 16 in all measures of physical function and other health-relatedoutcomes mentioned above (BASFI, SF-36 PCS, ASQoL and FACIT-Fatigue scores) were sustainedup to week 52 in both studies.

Extra-articular manifestation

In pooled data from BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS), at week 16, the proportionof patients developing a uveitis event was lower with bimekizumab (0.6%) compared to placebo(4.6%). The incidence of uveitis remained low with long-term treatment with bimekizumab (1.2/100patient-years in the pooled phase 2/3 studies).

The safety and efficacy of bimekizumab was evaluated in 1014 adult patients (at least 18 years of age)with moderate to severe Hidradenitis Suppurativa (HS) in two Phase 3 multicentre, randomised,double-blind, placebo-controlled studies (HS0003 - BE HEARD I and HS0004 - BE HEARD II).

Patients had a diagnosis of HS for at least 6 months with Hurley Stage II or Hurley Stage III disease,and with ≥5 inflammatory lesions (i.e. number of abscesses plus number of inflammatory nodules) andhad a history of inadequate response to a course of systemic antibiotics for the treatment of HS.

In both studies patients were randomised (2:2:2:1) to receive bimekizumab 320 mg every 2 weeks for48 weeks (320 mg Q2W/Q2W) or bimekizumab 320 mg every 4 weeks for 48 weeks (320 mg

Q4W/Q4W) or bimekizumab 320 mg every 2 weeks to week 16 followed by 320 mg every 4 weeks upto week 48 (320 mg Q2W/Q4W) or placebo to week 16 followed by bimekizumab 320 mg every 2weeks up to week 48. Concomitant oral antibiotic use was allowed if the patient was on a stable doseregimen of doxycycline, minocycline, or an equivalent systemic tetracycline for 28 days prior tobaseline.

The primary efficacy endpoint in both studies was the Hidradenitis Suppurativa Clinical Response 50(HiSCR50) at week 16, i.e. at least a 50% reduction in the total abscess and inflammatory nodule countwith no increase in abscess or draining tunnel count relative to baseline.

Baseline characteristics were consistent across both studies and reflective of a population withmoderate to severe HS. Patients had a median disease duration of 5.3 years (mean 8.0 years). Theproportions of Hurley Stage II and Stage III patients were 55.7% (50.3% in HS0003 and 61.1% in

HS0004) and 44.3% (49.7% in HS0003 and 38.9% in HS0004) respectively, and 8.5% were receivingconcomitant antibiotic therapy for HS. The mean baseline Dermatology Life Quality Index (DLQI)total score was 11.4. 56.8% of patients were female and the mean age of all patients was 36.6 years.79.7% of patients were White, and 10.8% were Black or African American. 45.6% of patients werecurrent smokers.

Treatment with bimekizumab resulted in clinically relevant improvement in disease activity comparedto placebo at week 16. Key efficacy results are shown in Table 12 and 13. The results in Table 12reflect the predefined primary analysis in which any systemic antibiotic use prior to week 16 resultedin imputation of nonresponse. In Table 13, only systemic antibiotic use considered by the Investigatorto be rescue treatment for HS resulted in imputation of nonresponse.

Table 12: Response in BE HEARD I and BE HEARD II at week 16 - primary analysisa

BE HEARD I BE HEARD II

Placebo BKZ 320 mg BKZ 320 mg Placebo BKZ BKZ 320 mg(N=72) Q4W Q2W (N=74) 320 mg Q4W Q2W(N=144) (N=289) (N=144) (N=291)

HiSCR50, % 28.7 45.3 47.8* 32.2 53.8* 52.0*(95% CI) (18.1, 39.3) (36.8, 53.8) (41.8, 53.7) (21.4, 42.9) (45.4, 62.1) (46.1, 57.8)

HiSCR75, % 18.4 24.7 33.4* 15.6 33.7* 35.7*(95% CI) (9.3, 27.5) (17.3, 32.1) (27.8, 39.1) (7.2, 24.0) (25.7, 41.7) (30.1, 41.3)

HSSDD worst skinpain responseb % 15.0 22.1 32.3 10.9 28.6 31.8(95% CI) (3.6, 26.5) (12.7, 31.4) (25.1, 39.5) (1.7, 20.1) (19.5, 37.8) (25.1, 38.4)a) Patients who take systemic antibiotics for any reason or who discontinue due to adverse event or lack of efficacy are treatedas non-responders at all subsequent visits for responder variables (or are subject to multiple imputation for continuousvariables). Other missing data were imputed via multiple imputation.b) Skin pain response, based on the threshold for within-patient clinically meaningful change (defined as at least a 3-pointdecrease from Baseline in Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) weekly worst skin pain score) at week16 among study participants with a score of ≥3 at Baseline. For BE HEARD I: N=46 for placebo, N=103 for BKZ Q4W and

N=190 for BKZ Q2W; BE HEARD II: N=49 for placebo, N=108 for BKZ Q4W and N=209 for BKZ Q2W.

*p<0.025 versus placebo, adjusted for multiplicity.

Table 13: Response in BE HEARD I and BE HEARD II at week 16 - supportive analysisa

BE HEARD I BE HEARD II

Placebo BKZ 320 mg BKZ 320 mg Placebo BKZ 320 mg BKZ 320 mg(N=72) Q4W Q2W (N=74) Q4W Q2W(N=144) (N=289) (N=144) (N=291)

HiSCR50, % 34.0 53.5 55.2 32.3 58.5 58.7(95% CI) (23.0, 45.1) (45.0, 62.0) (49.2, 61.1) (21.5, 43.1) (50.2, 66.8) (53.0, 64.5)

HiSCR75, % 18.3 31.4 38.7 15.7 36.4 39.7(95% CI) (9.3, 27.3) (23.5, 39.4) (32.9, 44.5) (7.2, 24.1) (28.3, 44.5) (34.0, 45.5)

HSSDD worst skinpain responseb % 16.1 25.3 36.7 11.1 32.9 36.7(95% CI) (4.5, 27.8) (16.0, 34.7) (29.4, 44.1) (1.8, 20.4) (23.5, 42.4) (29.8, 43.6)a) Post-hoc analysis (modified nonresponder imputation [mNRI]): Patients who take systemic antibiotics as rescue medicationfor HS as defined by the Investigator or who discontinue due to adverse event or lack of efficacy are treated as non-responders at all subsequent visits for responder variables (or are subject to multiple imputation for continuous variables).

Other missing data were imputed via multiple imputation.b) Skin pain response, based on the threshold for within-patient clinically meaningful change (defined as at least a 3-pointdecrease from Baseline in Hidradenitis Suppurativa Symptom Daily Diary (HSSDD) weekly worst skin pain score) at week16 among study participants with a score of ≥3 at Baseline. For BE HEARD I: N=46 for placebo, N=103 for BKZ Q4W and

N=190 for BKZ Q2W; BE HEARD II: N=49 for placebo, N=108 for BKZ Q4W and N=209 for BKZ Q2W.

In both studies, the onset of action of bimekizumab occurred as early as week 2.

The efficacy of bimekizumab was demonstrated regardless of prior biologics therapy and systemicantibiotic use at baseline.

Clinical responses were sustained through week 48 in both studies (see Table 14).

Table 14: Response in BE HEARD I and BE HEARD II at week 48 (mNRI*)

BE HEARD I BE HEARD II

BKZ 320 mg BKZ 320 mg BKZ 320 mg BKZ 320 mg BKZ 320 mg BKZ 320 mg

Q4W/Q4W Q2W/Q4W Q2W/Q2W Q4W/Q4W Q2W/Q4W Q2W/Q2W(N=144) (N=146) (N=143) (N=144) (N=146) (N=145)

HiSCR50, % 52.7 61.4 60.6 63.2 63.8 60.6

HiSCR75, % 40.5 44.7 47.6 53.9 48.8 47.3

* mNRI (modified non-responder imputation): Patients who take systemic antibiotics as rescue medication for HS as definedby the Investigator or who discontinue due to adverse event or lack of efficacy are treated as non-responders at all subsequentvisits for responder variables (or are subject to multiple imputation for continuous variables). Other missing data wereimputed via multiple imputation. This exploratory approach to handling missing data was performed post-hoc.

Across both studies, patients treated with bimekizumab experienced greater meaningful improvementcompared to placebo in their health-related quality of life as measured by the standard skin-specific

DLQI (Table 15).

Table 15: Health-related quality of life in BE HEARD I and BE HEARD II at week 16

BE HEARD I BE HEARD II

Placebo BKZ 320 mg BKZ 320 mg Placebo BKZ 320 mg BKZ 320 mg(N=72) Q4W Q2W (N=74) Q4W Q2W(N=144) (N=289) (N=144) (N=291)

DLQI total score

Mean cfba (SE) -2.9 (0.8) -5.4 (0.6) -5.0 (0.4) -3.2 (0.6) -4.5 (0.5) -4.6 (0.3)

DLQI total score ranges from 0 to 30 with higher scores indicating lower HRQoL.

Patients who take systemic antibiotics as rescue medication for HS as defined by the Investigator or who discontinue due toadverse event or lack of efficacy are subject to multiple imputation. Other missing data were imputed via multipleimputation.a) cfb: change from baseline

Improvement achieved at week 16 in health-related quality of life measurements with bimekizumabwere sustained through week 48.

The European Medicines Agency has deferred the obligation to submit the results of studies with

Bimzelx in one or more subsets of the paediatric population in psoriasis, chronic idiopathic arthritisand hidradenitis suppurativa (see section 4.2 for information on paediatric use).

The pharmacokinetic (PK) properties of bimekizumab were similar in patients with plaque psoriasis,psoriatic arthritis and axial spondyloarthritis (nr-axSpA and AS).

Based on population PK analyses and using a reference bodyweight of 90 kg, the bimekizumabapparent clearance and volume of distribution, respectively, in patients with hidradenitis suppurativawere estimated to be approximately 31 and 18 % higher than for the aforementioned indications, withan estimated half-life in HS of 20 days. Consequently, the median steady state trough concentration ata dose of 320 mg every 4 weeks was approximately 40 % lower in HS compared to other indications.

Based on population pharmacokinetic analysis, following a single subcutaneous dose of 320 mg inplaque psoriasis patients, bimekizumab reached a median (2.5th and 97.5th percentile) peak plasmaconcentration of 25 (12 -50) μg/mL, between 3 and 4 days post dose.

Population pharmacokinetic analysis showed that bimekizumab was absorbed with an averageabsolute bioavailability of 70.1% in healthy volunteers.

Based on simulated data, the median (2.5th and 97.5th percentile) peak and trough concentration atsteady-state following subcutaneous administration of 320 mg every 4 weeks are 43 (20-91) µg/mLand 20 (7-50) µg/mL respectively and steady-state is reached after approximately 16 weeks with every4 weeks dosing regimen. Compared with exposure after a single dose, the population pharmacokineticanalysis showed that patients exhibited a 1.74-fold increase in peak plasma concentrations and areaunder the curve (AUC) following repeated four weekly dosing.

After switching from the 320 mg every 4 weeks dosing regimen to 320 mg every 8 weeks dosingregimen at week 16, steady-state is achieved approximately 16 weeks after the switch. Median (2.5thand 97.5th percentile) peak and trough plasma concentrations are 30 (14 -60) μg/mL and 5 (1-16) μg/mL respectively.

Based on population pharmacokinetic analyses, the median (coefficient of variation %) volume ofdistribution (V/F) at steady state was 11.2 (30.5%) L in plaque psoriasis patients.

Bimekizumab is a monoclonal antibody and is expected to be degraded into small peptides and aminoacids via catabolic pathways in the same manner as endogenous immunoglobulins.

Based on population pharmacokinetic analyses, the median (coefficient of variation %) apparentclearance (CL/F) of bimekizumab was 0.337 L/day (32.7%) and the mean terminal elimination half-life of bimekizumab was 23 days in clinical studies in patients with plaque psoriasis.

Bimekizumab exhibited dose-proportional pharmacokinetics in patients with plaque psoriasis over adose range from 64 mg to 480 mg following multiple subcutaneous administrations, with apparentclearance (CL/F) being independent of dose.

A population pharmacokinetic/pharmacodynamic model was developed using all available data inmoderate to severe plaque psoriasis patients. The analysis showed that higher bimekizumabconcentrations are related to better Psoriasis Area and Severity Index (PASI) and Investigators Global

Assessment (IGA) response. A dose of 320 mg every 4 weeks was shown to be an appropriate dose forthe initial treatment period and 320 mg every 8 weeks thereafter is appropriate for the maintenanceperiod for the majority of moderate to severe plaque psoriasis patients (see Special Populations, Bodyweight).

Population pharmacokinetic modelling indicated that exposure decreased as body weight increased.

The average plasma concentration in adult patients weighing ≥120 kg following a 320 mgsubcutaneous injection was predicted to be at least 30% lower than in adult patients weighing 90 kg.

Dose adjustment may be appropriate in some patients (see section 4.2).

Based on population pharmacokinetic analysis with a limited number of elderly patients (n=355 forage ≥ 65 years and n= 47 for age ≥ 75 years), apparent clearance (CL/F) in elderly patients andpatients less than 65 years of age was similar. No dose adjustment is required (see section 4.2).

No specific studies have been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of bimekizumab. The renal elimination of intact bimekizumab, an IgG monoclonalantibody, is expected to be low and of minor importance. Similarly, IgGs are mainly eliminated viaintracellular catabolism and hepatic impairment is not expected to influence clearance ofbimekizumab. Based on population pharmacokinetic analyses, hepatic function markers(ALT/bilirubin) did not have any impact on bimekizumab clearance in patients with plaque psoriasis.

No clinically meaningful differences in bimekizumab exposure were observed in Japanese or Chinesesubjects compared to Caucasian subjects in a clinical pharmacokinetic study. No dose adjustment isrequired.

Population pharmacokinetic modelling indicated females may have 10% faster apparent clearance(CL/F) compared to males and it is not clinically meaningful. No dose adjustment is required.

Non-clinical data revealed no special hazard for humans based on tissue cross-reactivity testing,repeat-dose toxicity studies (including safety pharmacology endpoints and assessment of fertility-related endpoints) and evaluation of pre- and postnatal development in the cynomolgus monkey.

In cynomolgus monkeys, bimekizumab-related effects were limited to mucocutaneous changesconsistent with pharmacologic modulation of commensal microflora.

No mutagenicity or carcinogenicity studies were conducted with bimekizumab. However monoclonalantibodies are not expected to damage DNA or chromosomes. In a 26-week chronic toxicology studyin cynomolgus monkeys there were no pre-neoplastic or neoplastic lesions observed at a dose resultingin 109 times the human exposure at 320 mg every 4 weeks.

In a peri- and postnatal development study in the cynomolgus monkey, bimekizumab showed noeffects on gestation, parturition, infant survival, foetal and postnatal development when administeredthroughout organogenesis until parturition at a dose resulting in 27 times the human exposure at320 mg every 4 weeks based on AUC. At birth, serum bimekizumab concentrations in infant monkeyswere comparable to those of mothers.

Glycine

Sodium acetate trihydrate

Glacial acetic acid

Polysorbate 80

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

3 years

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The pre-filled syringe may be stored at room temperature (up to 25 °C) for a single period ofmaximum 25 days with protection from light. Once removed from the refrigerator and stored underthese conditions, discard after 25 days or by the expiry date printed on the container, whichever occursfirst. A field for the date is provided on the carton to record the date removed from the refrigerator.

Bimzelx 320 mg solution for injection in pre-filled syringe

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The pre-filled syringe may be stored at room temperature (up to 25 °C) for a single period ofmaximum 25 days with protection from light. Once removed from the refrigerator and stored underthese conditions, discard after 25 days or by the expiry date printed on the container, whichever occursfirst. A field for the date is provided on the carton to record the date removed from the refrigerator.

Store in a refrigerator (2 °C - 8 °C).

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Keep the pre-filled pen in the outer carton in order to protect from light.

The pre-filled pen may be stored at room temperature (up to 25 °C) for a single period of maximum25 days with protection from light. Once removed from the refrigerator and stored under theseconditions, discard after 25 days or by the expiry date printed on the container, whichever occurs first.

A field for the date is provided on the carton to record the date removed from the refrigerator.

Bimzelx 320 mg solution for injection in pre-filled pen

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the pre-filled pen in the outer carton in order to protect from light.

The pre-filled pen may be stored at room temperature (up to 25 °C) for a single period of maximum25 days with protection from light. Once removed from the refrigerator and stored under theseconditions, discard after 25 days or by the expiry date printed on the container, whichever occurs first.

A field for the date is provided on the carton to record the date removed from the refrigerator.

One mL pre-filled syringe (Type I glass) with a fluoropolymer-laminated bromobutyl rubber stopper,staked 27G, ½” thin wall needle, and a rigid needle shield (consisting of a thermoplastic elastomerneedle cover and a polypropylene rigid shield) assembled in an automatic needle guard.

Pack size of 1 pre-filled syringe.

Pack size of 2 pre-filled syringes.

Multipack containing 3 (3 packs of 1) pre-filled syringes.

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Bimzelx 320 mg solution for injection in pre-filled syringe

Two mL pre-filled syringe (Type I glass) with a fluoropolymer-laminated bromobutyl rubber stopper,staked 27G, ½” thin wall needle, and a rigid needle shield (consisting of a thermoplastic elastomerneedle cover and a polypropylene rigid shield) assembled in an automatic needle guard.

Pack size of 1 pre-filled syringe.

Multipack containing 3 (3 packs of 1) pre-filled syringes.

Not all pack sizes may be marketed.

One mL pre-filled pen containing a pre-filled syringe (Type I glass) with a fluoropolymer-laminatedbromobutyl rubber stopper, staked 27G, ½” thin wall needle, and a rigid needle shield consisting of athermoplastic elastomer needle cover and a polypropylene rigid shield.

Pack size of 1 pre-filled pen.

Pack size of 2 pre-filled pens.

Multipack containing 3 (3 packs of 1) pre-filled pens.

Multipack containing 4 (2 packs of 2) pre-filled pens.

Not all pack sizes may be marketed.

Bimzelx 320 mg solution for injection in pre-filled pen

Two mL pre-filled pen containing a pre-filled syringe (Type I glass) with a fluoropolymer-laminatedbromobutyl rubber stopper, staked 27G, ½” thin wall needle, and a rigid needle shield consisting of athermoplastic elastomer needle cover and a polypropylene rigid shield.

Pack size of 1 pre-filled pen.

Multipack containing 3 (3 packs of 1) pre-filled pens.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

UCB Pharma S.A.

Allée de la Recherche 60

B-1070 Bruxelles

Belgium

EU/1/21/1575/001

EU/1/21/1575/002

EU/1/21/1575/003

EU/1/21/1575/004

Bimzelx 320 mg solution for injection in pre-filled syringe

EU/1/21/1575/009

EU/1/21/1575/010

EU/1/21/1575/005

EU/1/21/1575/006

EU/1/21/1575/007

EU/1/21/1575/008

Bimzelx 320 mg solution for injection in pre-filled pen

EU/1/21/1575/011

EU/1/21/1575/012

Date of first authorisation: 20 August 2021

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.