14 CLINICAL STUDIES

14.1 Plaque Psoriasis

Three multicenter, randomized, double-blind trials [Trial Ps-1 (NCT03370133), Trial Ps-2 (NCT03410992), and Trial Ps-3 (NCT03412747)] enrolled a total of 1,480 subjects 18 years of age and older with moderate to severe plaque psoriasis who had a body surface area (BSA) involvement of ≥10%, an Investigator's Global Assessment (IGA) score of ≥3 ("moderate") in the overall assessment of psoriasis on a severity scale of 0 to 4, and a Psoriasis Area and Severity Index (PASI) score ≥12.

In Trial Ps-1, 567 subjects were randomized to receive either BIMZELX 320 mg by subcutaneous injection every 4 weeks, ustekinumab (for subjects weighing ≤100kg, 45 mg initially and 4 weeks later, then every 12 weeks; for subjects weighing >100kg, 90 mg initially and 4 weeks later, then every 12 weeks), or placebo through Week 52. At Week 16, subjects originally randomized to placebo received BIMZELX 320 mg every 4 weeks through Week 52.

In Trial Ps-2, 435 subjects were randomized to either BIMZELX 320 mg by subcutaneous injection every 4 weeks or placebo. At Week 16, subjects who achieved a PASI 90 response continued into a 40-week randomized withdrawal period. Subjects originally randomized to BIMZELX 320 mg every 4 weeks were re-randomized to either BIMZELX 320 mg every 4 weeks or BIMZELX 320 mg every 8 weeks or placebo. Subjects originally randomized to placebo continued to receive placebo if they were PASI 90 responders. Subjects who did not achieve a PASI 90 response at week 16 entered an open-label escape arm and received BIMZELX 320 mg every 4 weeks for 12 weeks. Subjects who relapsed, defined as having a less than PASI 75 response compared to baseline, during the randomized withdrawal period also entered the 12-week escape arm.

In Trial Ps-3, 478 subjects were randomized to receive either BIMZELX 320 mg by subcutaneous injection every 4 weeks through week 56, BIMZELX 320 mg every 4 weeks through week 16 followed by BIMZELX every 8 weeks through week 56, or adalimumab (80 mg as an initial dose followed by 40 mg every other week starting 1 week after initial dose through Week 24) followed by BIMZELX 320 mg every 4 weeks through Week 56.

In Trial Ps-1, Trial Ps-2, and Trial Ps-3, 71% of the subjects were male and 84% of the subjects were White, with a mean age of 45 years and a mean weight of 89 kg. At baseline, subjects had a median baseline PASI score of 18, median baseline for BSA of 20%, and baseline IGA score of 4 ("severe") in 33% of subjects. A total of 93% subjects had psoriasis of the scalp (Scalp IGA score of ≥1) and a total of 26% of subjects had a history of psoriatic arthritis. Additionally, 38% had received prior biologic therapy.

Clinical Response at Week 16 (Trial Ps-1 and Trial Ps-2)

Trial Ps-1 and Trial Ps-2 responses at Week 16 compared to placebo for the two co-primary endpoints:

The proportion of subjects who achieved an IGA score of 0 ("clear") or 1 ("almost clear") with at least a 2-grade improvement from baseline
The proportion of subjects who achieved at least a 90% reduction from baseline PASI (PASI 90)

Secondary endpoints included the proportion of subjects who achieved PASI 100, IGA 0, and Scalp IGA response (defined as Scalp IGA score of 0 [clear] or 1 [almost clear] with at least 2-grade of improvement from baseline) at Week 16, and PASI 75 at Week 4. In addition, secondary endpoints included assessment of psoriasis symptoms (itching, pain, and scaling) measured by the Patient Symptom Diary (PSD) at Week 16.

The proportion of subjects who achieved IGA 0 or 1, PASI 90, IGA 0, and PASI 100 response at Week 16 are presented in Table 3.

Table 3: Efficacy Results at Week 16 in BIMZELX or Placebo-Treated Adults with Plaque Psoriasis in Trial Ps-1 and Trial Ps-2
	Trial Ps-1		Trial Ps-2
	BIMZELX 320 mg every 4 weeks (N=321) n (%)	Placebo (N=83) n (%)	BIMZELX 320 mg every 4 weeks (N=349) n (%)	Placebo (N=86) n (%)
* Co-primary endpoints
IGA 0 or 1 ("clear" or "almost clear")*	270 (84%)	4 (5%)	323 (93%)	1 (1%)
Difference (95% CI)	79% (73%, 85%)		91% (88%, 95%)
PASI 90*	273 (85%)	4 (5%)	317 (91%)	1 (1%)
Difference (95% CI)	80% (74%, 86%)		90% (86%, 93%)
IGA 0 ("clear")	188 (59%)	0 (0%)	243 (70%)	1 (1%)
Difference (95% CI)	59% (53%, 64%)		69% (64%, 74%)
PASI 100	188 (59%)	0 (0%)	238 (68%)	1 (1%)
Difference (95% CI)	59% (53%, 64%)		67% (62%, 73%)

Examination of age, gender, race, baseline IGA score and previous treatment with systemic or biologic agents did not identify differences in response to BIMZELX among these subgroups at Week 16.

A greater proportion of subjects randomized to BIMZELX achieved PASI 75 at Week 4 in both trials compared to placebo. In Trial Ps-1, 77% of subjects treated with BIMZELX achieved PASI 75 compared to 2% treated with placebo. In Trial Ps-2, 76% of subjects treated with BIMZELX achieved PASI 75 compared to 1% treated with placebo.

Among subjects with Scalp IGA score of at least 2 at baseline, a greater proportion of subjects randomized to BIMZELX achieved Scalp IGA response at Week 16 in both trials compared to placebo. In Trial Ps-1, 84% (240/285) of subjects treated with BIMZELX achieved Scalp IGA response compared to 15% (11/72) of placebo treated subjects. In Trial Ps-2, 92% (286/310) of subjects treated with BIMZELX achieved Scalp IGA response compared to 7% (5/74) of placebo treated subjects.

Maintenance and Durability of Response

In Trial Ps-2, subjects randomized to BIMZELX every 4 weeks at Week 0 and who were PASI 90 responders at Week 16 were re-randomized to either continue treatment with BIMZELX every 4 weeks, switched to BIMZELX every 8 weeks, or be withdrawn from therapy (i.e., received placebo).

Figure 1 and Figure 2 present the percentage of subjects maintaining IGA score of 0 ("Clear") or 1 ("Almost Clear") and PASI 90, respectively, through Week 56 after re-randomization at Week 16.

Figure 1: Percentage of Subjects Maintaining IGA 0 or 1 through Week 56 after Re-Randomization at Week 16

For IGA 0 or 1 responders at Week 16 who were re-randomized to treatment withdrawal (i.e., placebo), the median time to loss of IGA 0 or 1 response was approximately 24 weeks. Among these subjects with IGA score of 2 at retreatment, 58% (14/24) achieved IGA score of 0 within 12 weeks of restarting treatment with BIMZELX 320 mg every 4 weeks. Among these subjects with IGA score ≥ 3 at retreatment, 87% (34/39) regained IGA 0 or 1 response with at least 2-grade improvement from retreatment within 12 weeks of restarting treatment with BIMZELX 320 mg every 4 weeks.

Figure 2: Percentage of Subjects Maintaining PASI 90 through Week 56 after Re-Randomization at Week 16

For PASI 90 responders at Week 16 who were re-randomized to treatment withdrawal (i.e., placebo), the median time to loss of PASI 90 response was approximately 24 weeks.

Patient Reported Outcomes

Greater improvements in itch, pain, and scaling at Week 16 with BIMZELX compared to placebo were observed in both trials as measured by the Patient Symptom Diary (PSD).

14.2 Psoriatic Arthritis

The safety and efficacy of BIMZELX were assessed in 1,112 subjects in two multicenter, randomized, double-blind, placebo-controlled studies [Trial PsA-1 (NCT 03895203) and Trial PsA-2 (NCT 03896581)] in subjects 18 years and older with active psoriatic arthritis (PsA).

Subjects in these studies had a diagnosis of PsA of at least 6 months based on Classification Criteria for Psoriatic Arthritis (CASPAR), a median duration of 4.6 years at baseline, and active disease with ≥3 tender joint count and ≥3 swollen joint count. Subjects with each subtype of PsA were enrolled in these studies, including polyarticular symmetric arthritis (63.5%), oligoarticular asymmetric arthritis (25.9%), distal interphalangeal joint predominant (4.4%), spondylitis predominant (4.2%), and arthritis mutilans (1.5%). At baseline, 56% of subjects had ≥3% Body Surface Area (BSA) with active plaque psoriasis. At baseline across both studies, 32% and 12% of subjects had enthesitis and dactylitis, respectively, 58% of subjects had psoriatic nail disease, and 53% of subjects were receiving concomitant methotrexate.

The PsA-1 study evaluated 852 biologic-naïve subjects, who were treated with either BIMZELX 160 mg every 4 weeks up to Week 52, adalimumab 40 mg every 2 weeks up to Week 52 (active reference arm), or placebo. Subjects receiving placebo were switched to BIMZELX every 4 weeks at Week 16 to Week 52. In this study, 78% of subjects had received prior treatment with ≥ 1 conventional DMARDs (cDMARDs), and 22 % of subjects had no prior treatment with cDMARDs. At baseline, 58% of subjects were receiving concomitant methotrexate (MTX), 11% were receiving concomitant cDMARDs other than MTX, and 31% were receiving no cDMARDs. The PsA-2 study evaluated 400 anti-TNFα experienced subjects (inadequate response or intolerance to treatment), who were treated with BIMZELX 160 mg every 4 weeks or placebo up to Week 16. In this study, 43% of subjects were receiving concomitant MTX, 8% were receiving concomitant cDMARDs other than MTX, and 50% were receiving no cDMARDs.

For both studies, the primary endpoint was the proportion of subjects who achieved an America College of Rheumatology (ACR) 50 response at Week 16.

Clinical Response

In both studies, treatment with BIMZELX resulted in significant improvement in disease activity, as measured by ACR, compared to placebo at Week 16 (see Table 4). Responses in Trial PsA-2 (anti-TNF experienced) were similar to Trial PsA-1.

Table 4: Clinical Responses at Week 16 in Trial PsA-1 and Trial PsA-2
	Trial PsA-1 – bDMARD naïve			Trial PsA-2 – anti-TNFα experienced
Endpoint	BIMZELX 160 mg Q4W N=431 n (%)	Placebo N=281 n (%)	Difference from Placebo* (95% CI)	BIMZELX 160 mg Q4W N=267 n (%)	Placebo N=133 n (%)	Difference from Placebo* (95% CI)
CI= confidence interval
* 95% CI based on normal approximation † Multiplicity-controlled p<0.001 ‡ Exact 95% CI used
ACR 20 Response
Week 16	268 (62.2)	67 (23.8)	38.3 (31.6, 45.1)	179 (67.0)	21 (15.8)	51.3 (42.9, 59.6)
ACR 50 Response
Week 16	189 (43.9)†	28 (10.0)	33.9 (28.0, 39.7)	116 (43.4)†	9 (6.8)	36.7 (29.4, 44.0)
ACR 70 Response
Week 16	105 (24.4)	12 (4.3)	20.1 (15.4, 24.8)	71 (26.6)	1 (0.8)	25.8 (15.6, 35.7)‡

The percentage of subjects achieving ACR50 responses in Trial PsA-1 by visit through Week 16 is shown in Figure 3. Similar responses were seen in Trial PsA-2 up to Week 16.

Figure 3: Percent of Subjects Achieving ACR 50 Responses in Trial PsA-1 through Week 16

Figure 3: Percent of Subjects Achieving ACR 50 Responses in Trial PsA-1 through Week 16

The results of the components of the ACR response criteria are shown in Table 5.

Table 5: Mean change from Baseline in ACR Component Scores at Week 16 in Trial PsA-1 and Trial PsA-2
	Trial PsA-1 – bDMARD naïve		Trial PsA-2 – anti-TNFα experienced
	Placebo (N=281)	BIMZELX 160 mg Q4W (N=431)	Placebo (N=133)	BIMZELX 160 mg Q4W (N=267)
Multiple Imputation (MI) is used for all endpoints presented in Table 5.
* p<0.001 reference-based imputation versus placebo adjusted for multiplicity.
Number of Swollen Joints
Baseline	9.5	9.0	10.3	9.7
Mean change at Week 16	-3.0	-6.6	-2.0	-7.0
Number of Tender Joints
Baseline	17.1	16.8	19.3	18.4
Mean change at Week 16	-3.2	-10.0	-2.4	-10.9
Patient's Assessment of Pain
Baseline	56.8	53.7	61.7	58.3
Mean change at Week 16	-6.2	-23.6	-4.5	-27.7
Patient's Global Assessment
Baseline	58.6	54.4	63.0	60.5
Mean change at Week 16	-7.7	-26.3	-5.5	-31.8
Physician Global Assessment
Baseline	57.3	57.2	57.7	59.3
Mean change at Week 16	-12.5	-37.4	-6.8	-49.4
Health Assessment Questionnaire- Disability Index (HAQ-DI)
Baseline	0.9	0.8	1.0	1.0
Mean Change at Week 16	-0.1	-0.3*	-0.1	-0.4*
High Sensitivity C-reactive Protein (hsCRP) mg/L
Baseline	11.4	8.7	11.6	12.4
Mean Change at Week 16	-2.4	-4.2	3.6	-7.0

Treatment with BIMZELX resulted in improvement in dactylitis and enthesitis in subjects with pre-existing dactylitis or enthesitis, compared to placebo.

In subjects with coexistent plaque psoriasis receiving BIMZELX, the skin lesions of psoriasis improved with treatment, relative to placebo, as measured by the Psoriasis Area Severity Index (PASI 90) at Week 16.

Radiographic Response

In Trial PsA-1, inhibition of progression of structural damage was assessed radiographically and expressed 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 6).

BIMZELX significantly inhibited the rate of progression of joint damage at Week 16 in the overall population compared to placebo. The change from Baseline in erosion subscores contributed more to the change from Baseline in vdHmTSS total score than the change from Baseline in joint narrowing subscore. The percentage of subjects with no radiographic joint damage progression (defined as a change from baseline in mTSS of ≤0.0) from randomization to Week 16 was 77% for BIMZELX and 69% for placebo in the overall population. Similar responses were achieved in the population with elevated hsCRP and/or at least 1 bone erosion (75% for BIMZELX and 67% for placebo).

Table 6: Change in vdHmTSS in PsA-1 at Week 16
	Placebo	BIMZELX 160 mg Q4W	Difference from Placebo (95% CI)*
* Unadjusted differences are shown † p≤0.001 versus placebo. p-values are based on reference-based imputation using difference in LS Mean using an ANCOVA model with treatment, bone erosion at Baseline and region as fixed effects and Baseline score as a covariate.
Overall population	(N=269)	(N=420)
Baseline mean (SE)	12.34 (1.37)	12.47 (1.46)
Mean change from baseline at Week 16 (SE)	0.32 (0.09)	0.04 (0.04)†	-0.26 (-0.29, -0.23)

Physical Function

In both studies, subjects treated with BIMZELX showed statistically significant improvement from baseline in physical function compared with placebo as assessed by HAQ-DI at Week 16 (see Table 5). In both studies, a greater proportion of subjects achieved a reduction of at least 0.35 in HAQ-DI score from baseline in the BIMZELX group compared with placebo at Week 16.

Other Health Related Outcomes

Fatigue was assessed by Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue). Additionally, in both studies at Week 16, subjects treated with BIMZELX showed improvements in FACIT-Fatigue scores.

14.3 Non-Radiographic Axial Spondyloarthritis

The efficacy and safety were assessed in 254 patients in one randomized, double-blind, placebo-controlled study [Trial nr-axSpA-1 (NCT03928704)] in adult subjects 18 years of age and older with active non-radiographic axial spondyloarthritis. Subjects had to have objective signs of inflammation with elevated C-reactive protein (CRP) level and/or evidence of sacroiliitis on Magnet Resonance Imaging (MRI). Subjects met ASAS classification criteria for axial spondyloarthritis and have active disease as defined by BASDAI greater than or equal to 4, spinal pain of greater than or equal to 4 (0-10 numeric rating scale (NRS)), and no definitive radiographic evidence of structural damage in the sacroiliac joints. At baseline, 73% of subjects had enthesitis. Subjects also had a history of inadequate response to 2 different non-steroidal anti-inflammatory drugs (NSAIDs), or intolerance or contraindication to NSAIDs. Approximately 24% of subjects were on concomitant cDMARDs. Overall, 11% of subjects had received previous treatment (failed or were intolerant to) with anti-TNF alpha agents.

Subjects were randomized to receive BIMZELX 160 mg or placebo every 4 weeks up to the completion of Week 16 assessments. Starting at Week 16, all subjects received BIMZELX every 4 weeks up to Week 52. The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society (ASAS 40) at Week 16.

Clinical Response

In Trial nr-axSpA-1, treatment with BIMZELX resulted in significant improvements in the measure of disease activity compared to placebo at Week 16 (Table 7).

Table 7: Clinical Response in Trial nr-axSpA-1 at Week 16
	BIMZELX 160 mg Q4W (N=128)	Placebo (N=126)	Difference from placebo (95% CI)*
	n (%)	n (%)
NRI is used CI= confidence interval
* 95% CI based on normal approximation † Multiplicity-controlled p<0.001
ASAS 40 response	61 (47.7%)†	27 (21.4%)	26.2 (15.0, 37.5)
ASAS 20 response	88 (68.8%)†	48 (38.1%)	30.7 (19.0, 42.3)

Similar responses were seen regardless of prior anti-TNF alpha therapy. Treatment with BIMZELX resulted in improvement in enthesitis in subjects with pre-existing enthesitis.

The results of the main components of the ASAS 40 response criteria and other measures of disease activity are shown in Table 8.

Table 8: Components of the ASAS 40 Response Criteria and Other Measures of Disease Activity in nr-axSpA Subjects at Baseline and Week 16 in Trial nr-axSpA-1
	BIMZELX 160 mg Q4W (N= 128)	Placebo (N=126)
BASFI = Bath Ankylosing Spondylitis Functional Index
BASMI = Bath Ankylosing Spondylitis Metrology Index
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index
MI is used for all endpoints presented in Table 8
* Multiplicity-controlled p<0.001 † Inflammation is the mean of patient-reported stiffness self-assessments (questions 5 and 6) in BASDAI
ASAS Components
- Patient Global Assessment (0-10)
Baseline	7.1	6.9
Mean Change from Baseline	-3.2	-1.4
- Total Spinal Pain (0-10)
Baseline	7.3	7.1
Mean Change from Baseline	-3.4	-1.7
- BASFI (0-10)
Baseline	5.5	-2.5*
Mean Change from Baseline	5.3	-1.0
- Inflammation (0-10)†
Baseline	7.0	6.9
Mean Change from Baseline	-3.6	-1.9
Other Measures of Disease Activity
BASDAI Score
Baseline	6.9	6.7
Mean Change from Baseline	-3.1*	-1.5
BASMI
Baseline	2.9	3.0
Mean Change from Baseline	-0.4	-0.1
hsCRP (mg/L)
Baseline	11.1	10.2
Mean Change from Baseline	-6.7	0.0

The percentage of subjects achieving ASAS 40 responses in Trial nr-axSpA-1 by visit through Week 16 is shown in Figure 4.

Figure 4: Percent of Subjects Achieving ASAS 40 Responses in Trial nr-axSpA-1 Week 16

Health Related Quality of Life

BIMZELX treated subjects showed significantly greater improvement compared to subjects receiving placebo at Week 16 in health-related quality of life as measured by the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) score.

14.4 Ankylosing Spondylitis

The efficacy and safety were assessed in 332 patients in one randomized, double-blind, placebo-controlled study [Trial AS-1 (NCT03928743)] in adult subjects 18 years of age and older with active ankylosing spondylitis. Subjects had to have documented radiologic evidence (x-ray) fulfilling the Modified New York criteria for AS. Subjects had active disease as defined by BASDAI ≥4 and spinal pain ≥4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2). Subjects also had a history of inadequate response to 2 different non-steroidal anti-inflammatory drugs (NSAIDs), or intolerance or contraindication to NSAIDs. Approximately 20% of subjects were on concomitant cDMARDs. Overall, 16% of subjects had received previous treatment (failed or were intolerant to) with anti-TNF alpha agents.

Subjects were randomized 2:1 to receive BIMZELX 160 mg or placebo every 4 weeks up to the completion of Week 16 assessments. Starting at Week 16, all subjects received BIMZELX every 4 weeks up to Week 52. The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society (ASAS 40) at Week 16.

Clinical Response

In Trial AS-1, treatment with BIMZELX resulted in significant improvements in the measure of disease activity compared to placebo at Week 16 (Table 9).

Table 9: Clinical Response in Trial AS-1 at Week 16
	BIMZELX 160 mg Q4W (N=221)	Placebo (N=111)	Difference from placebo (95% CI)*
	n (%)	n (%)
NRI is used CI= confidence interval
* 95% CI based on normal approximation † Multiplicity-controlled p<0.001
ASAS 40 response	99 (44.8%)†	25 (22.5%)	22.3 (12.1, 32.4)
ASAS 20 response	146 (66.1%)†	48 (43.2%)	22.8 (11.7, 34.0)

Similar responses were seen regardless of prior anti-TNF alpha therapy. Treatment with BIMZELX resulted in improvement in enthesitis in subjects with pre-existing enthesitis.

The results of the main components of the ASAS 40 response criteria and other measures of disease activity are shown in Table 10.

Table 10: Components of the ASAS 40 Response Criteria and Other Measures of Disease Activity in Ankylosing Spondylitis Subjects at Baseline and Week 16 in Trial AS-1
	BIMZELX 160 mg Q4W (N= 221)	Placebo (N=111)
BASFI = Bath Ankylosing Spondylitis Functional Index
BASMI = Bath Ankylosing Spondylitis Metrology Index
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index
MI is used for all endpoints presented in Table 10
* Multiplicity-controlled p<0.001 † Inflammation is the mean of patient-reported stiffness self-assessments (questions 5 and 6) in BASDAI.; ‡ Multiplicity-controlled p<0.006
ASAS Components
- Patient Global Assessment (0-10)
Baseline	6.6	6.7
Mean Change from Baseline	-2.7	-1.6
- Total Spinal Pain (0-10)
Baseline	7.1	7.2
Mean Change from Baseline	-3.3	-1.9
- BASFI (0-10)
Baseline	5.3	5.2
Mean Change from Baseline	-2.2*	-1.1
- Inflammation (0-10)†
Baseline	6.7	6.8
Mean Change from Baseline	-3.2	-2.1
Other Measures of Disease Activity
BASDAI Score
Baseline	6.4	6.5
Mean Change from Baseline	-2.9*	-1.9
BASMI
Baseline	3.9	3.8
Mean Change from Baseline	-0.5‡	-0.2
hsCRP (mg/L)
Baseline	14.7	13.6
Mean Change from Baseline	-8.6	-2.2

The percentage of subjects achieving ASAS 40 responses in Trial AS-1 by visit through Week 16 is shown in Figure 5.

Figure 5: Percent of Subjects Achieving ASAS 40 Responses in Trial AS-1 Through Week 16

Health Related Quality of Life

BIMZELX treated subjects showed significantly greater improvement compared to subjects receiving placebo at Week 16 in health-related quality of life as measured by the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) score.

14.5 Hidradenitis Suppurativa

The safety and efficacy of BIMZELX were assessed in two Phase 3 multicenter, randomized, double-blind, placebo-controlled trials [Trial HS-1 (NCT04242446) and Trial HS-2 (NCT04242498)] in 1,014 adult subjects with moderate to severe HS of 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 (AN count)], and a history of inadequate response to a course of systemic antibiotics for the treatment of HS.

Subjects received BIMZELX 320 mg every 2 weeks (Q2W) for 48 weeks, or BIMZELX 320 mg every 4 weeks (Q4W) up to Week 48, or BIMZELX 320 mg Q2W to Week 16, followed by 320 mg Q4W up to Week 48, or placebo. At Week 16, subjects receiving placebo were switched to BIMZELX 320 mg Q2W to Week 48. Concomitant oral doxycycline, minocycline, or an equivalent systemic tetracycline for HS was allowed if the subject was on a stable dose regimen for 28 days prior to baseline.

In these trials, at baseline the mean age of all subjects was 37 years, 57% of subjects were female, 80% were White, 11% were Black or African American, and 4% were Asian; for ethnicity, 7% identified as Hispanic or Latino. Of the subjects enrolled in trials conducted in the United States, 33% were Black or African American. The mean BMI was 33, and 46% were current smokers. Subjects had a median disease duration of 5 years. Overall, 9% of subjects were receiving concomitant antibiotic therapy for HS, and 19% of subjects had received previous treatment with biologics. The proportion of Hurley Stage II and Stage III subjects were 56% and 44%, respectively. Additionally, the mean number of draining tunnels was 3.6 and mean AN count was 16.3.

The primary efficacy endpoint in both trials was the Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at Week 16, defined by at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining tunnel count relative to baseline. Secondary endpoints included the proportion of subjects who achieved HiSCR75 and HS-specific skin pain response as assessed by a 0 to 10 numeric rating scale (NRS).

Clinical Response at Week 16 (Trials HS-1 and HS-2)

In both trials, a higher proportion of BIMZELX-treated subjects achieved HiSCR50 and HiSCR75 compared to placebo (see Table 11).

Table 11: Efficacy Results in Adults with HS in Trials HS-1 and HS-2 at Week 16 *
	Trial HS-1		Trial HS-2
	BIMZELX 320mg Q2W (N=289)	Placebo (N=72)	BIMZELX 320 mg Q2W (N=291)	Placebo (N=74)
* Subjects who initiated systemic antibiotics (new antibiotic or change in the dose/type of current antibiotic) for any reason or who discontinued due to adverse event or lack of efficacy are treated as non-responders at all subsequent visits. Other missing data were imputed via multiple imputation.
HiSCR50	48%	29%	52%	32%
Difference (95% CI)	18% (6%, 30%)		20% (8%, 32%)
HiSCR75	33%	18%	36%	16%
Difference (95% CI)	15% (4%, 27%)		20% (10%, 31%)

Examination of age, gender, race, disease duration, weight, prior biologic therapy, systemic antibiotic use at baseline, Hurley stage, and smoking status did not identify meaningful differences in response to BIMZELX among these subgroups at Week 16.

Figure 6 presents the proportion of subjects achieving HiSCR50 response in Trials HS-1 and HS-2 by visit through Week 16.

Figure 6: HiSCR50 Response through Week 16 in Adults with HS in Trials HS-1 and HS-2

Subjects who initiated systemic antibiotics (new antibiotic or change in the dose/type of current antibiotic) for any reason through Week 16 or who discontinued due to adverse event or lack of efficacy are treated as non-responders at all subsequent visits. Other missing data were imputed via multiple imputation.

BIMZELX was associated with an improvement in patient-reported worst skin pain (lesion pain) based on the achievement of a reduction of at least 3 points (as measured on a 0 to 10 NRS) compared to placebo at Week 16.